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[0] Schmidt EM, McIntosh JS, Durelli L, Bak MJ, Fine control of operantly conditioned firing patterns of cortical neurons.Exp Neurol 61:2, 349-69 (1978 Sep 1)[1] Serruya MD, Hatsopoulos NG, Paninski L, Fellows MR, Donoghue JP, Instant neural control of a movement signal.Nature 416:6877, 141-2 (2002 Mar 14)[2] Fetz EE, Operant conditioning of cortical unit activity.Science 163:870, 955-8 (1969 Feb 28)[3] Fetz EE, Finocchio DV, Operant conditioning of specific patterns of neural and muscular activity.Science 174:7, 431-5 (1971 Oct 22)[4] Fetz EE, Finocchio DV, Operant conditioning of isolated activity in specific muscles and precentral cells.Brain Res 40:1, 19-23 (1972 May 12)[5] Fetz EE, Baker MA, Operantly conditioned patterns on precentral unit activity and correlated responses in adjacent cells and contralateral muscles.J Neurophysiol 36:2, 179-204 (1973 Mar)

[0] Suner S, Fellows MR, Vargas-Irwin C, Nakata GK, Donoghue JP, Reliability of signals from a chronically implanted, silicon-based electrode array in non-human primate primary motor cortex.IEEE Trans Neural Syst Rehabil Eng 13:4, 524-41 (2005 Dec)

[0] Westby GW, Wang H, A floating microwire technique for multichannel chronic neural recording and stimulation in the awake freely moving rat.J Neurosci Methods 76:2, 123-33 (1997 Oct 3)

[0] Hochberg LR, Serruya MD, Friehs GM, Mukand JA, Saleh M, Caplan AH, Branner A, Chen D, Penn RD, Donoghue JP, Neuronal ensemble control of prosthetic devices by a human with tetraplegia.Nature 442:7099, 164-71 (2006 Jul 13)

[0] Mehring C, Rickert J, Vaadia E, Cardosa de Oliveira S, Aertsen A, Rotter S, Inference of hand movements from local field potentials in monkey motor cortex.Nat Neurosci 6:12, 1253-4 (2003 Dec)

[0] Rousche PJ, Normann RA, Chronic recording capability of the Utah Intracortical Electrode Array in cat sensory cortex.J Neurosci Methods 82:1, 1-15 (1998 Jul 1)

[0] Bergman H, Wichmann T, DeLong MR, Reversal of experimental parkinsonism by lesions of the subthalamic nucleus.Science 249:4975, 1436-8 (1990 Sep 21)

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ref: -0 tags: tissue response indwelling implants dialysis kozai date: 04-04-2018 00:28 gmt revision:1 [0] [head]

PMID-25546652 Brain Tissue Responses to Neural Implants Impact Signal Sensitivity and Intervention Strategies

  • (Interesting): eight identical electrode arrays implanted into the same region of different animals have shown that half the arrays continue to record neural signals for >14 weeks while in the other half of the arrays, single-unit yield rapidly degraded and ultimately failed over the same timescale.
  • In another study, aimed at uncovering the time course of insertion-related bleeding and coagulation, electrodes were implanted into the cortex of rats at varying time intervals (−120, −90, −60, −30, −15, and 0 min) using a micromanipulator and linear motor with an insertion speed of 2 mm/s.40 The results showed dramatic variability in BBB leakage that washed out any trend (Figure 3), suggesting that a separate underlying cause was responsible for the large inter- and intra-animal variability.

{1402}
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ref: -0 tags: recurrent cortical model adaptation gain V1 LTD date: 03-27-2018 17:48 gmt revision:1 [0] [head]

PMID-18336081 Adaptive integration in the visual cortex by depressing recurrent cortical circuits.

  • Mainly focused on the experimental observation that decreasing contrast increases latency to both behavioral and neural response (latter in the later visual areas..)
  • Idea is that synaptic depression in recurrent cortical connections mediates this 'adaptive integration' time-constant to maintain reliability.
  • Model also explains persistent activity after a flashed stimulus.
  • No plasticity or learning, though.
  • Rather elegant and well explained.

{1401}
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ref: -2016 tags: somatostatin interneurons review date: 02-11-2018 18:08 gmt revision:0 [head]

PMID-27225074 Somatostatin-expressing neurons in cortical networks.

  • Urban-Ciecko J1, Barth AL1.
  • High (~ 10hz) tonic (constitutive) firing rate. All GABA.
  • Somatostatin, a neuropeptide, is of ill-defined role. Unknown when it is released.
  • SST interneurons receive diffuse input from cortical pyramidal cells, but each synapse is of low strength.
  • SST intererneurons are frequently electrically connected through gap junctions, but almost never through electrical synapses. The resulting network can extend for hundreds of microns, and has been shown to cause synchronized firing when cells are active.
  • Common anesthetics (isoflurane, urethane) profoundly silence the SSTs.
  • Wide diversity of axonal and dendritic branching patterns, targeting both apical (20%) and distal pyramidal cell dendrites.
  • SST neuron activity is reduced in Dravet syndrome.
  • SST neurons have also been implicated in schizophrenia; affected individuals show decreased SST mRNA and mislocalization of SST interneurons.

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ref: -0 tags: NET probes SU-8 microfabrication sewing machine carbon fiber electrode insertion mice histology 2p date: 12-29-2017 04:38 gmt revision:1 [0] [head]

PMID-28246640 Ultraflexible nanoelectronic probes form reliable, glial scar–free neural integration

  • SU-8 asymptotic H2O absorption is 3.3% in PBS -- quite a bit higher than I expected, and higher than PI.
  • Faced yield problems with contact litho at 2-3um trace/space.
  • Good recordings out to 4 months!
  • 3 minutes / probe insertion.
  • Fab:
    • Ni release layer, Su-8 2000.5. "excellent tensile strength" --
      • Tensile strength 60 MPa
      • Youngs modulus 2.0 GPa
      • Elongation at break 6.5%
      • Water absorption, per spec sheet, 0.65% (but not PBS)
    • 500nm dielectric; < 1% crosstalk; see figure S12.
    • Pt or Au rec sites, 10um x 20um or 30 x 30um.
    • FFC connector, with Si substrate remaining.
  • Used transgenic mice, YFP expressed in neurons.
  • CA glue used before metabond, followed by Kwik-sil silicone.
  • Neuron yield not so great -- they need to plate the electrodes down to acceptable impedance. (figure S5)
    • Measured impedance ~ 1M at 1khz.
  • Unclear if 50um x 1um is really that much worse than 10um x 1.5um.
  • Histology looks realyl great, (figure S10).
  • Manuscript did not mention (though the did at the poster) problems with electrode pull-out; they deal with it in the same way, application of ACSF.

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ref: Kim-2008.01 tags: PEDOT review soft date: 12-29-2017 04:34 gmt revision:4 [3] [2] [1] [0] [head]

PMID-21204405 Soft, Fuzzy, and Bioactive Conducting Polymers for Improving the Chronic Performance of Neural Prosthetic Devices.

  • lays out the soft electrode approach (obviously).
  • Extensive discussion of conductive polymer plating methods for neural electrodes.

____References____

[0] Kim DH, Richardson-Burns S, Povlich L, Abidian MR, Spanninga S, Hendricks JL, Martin DC, Soft, Fuzzy, and Bioactive Conducting Polymers for Improving the Chronic Performance of Neural Prosthetic Devicesno Source no Volume no Issue no Pages (2008)

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ref: Salcman-1973.07 tags: Salcman MEA microelectrodes chronic recording glass cyanocrylate date: 12-29-2017 04:33 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

PMID-4708761 Design, Fabrication, and In Vivo Behavior of Chronic Recording Intracortical Microelectrodes

  • Teflon-coated 25um Pt-Ir (90/10)
  • Heat fuse this with a glass micropipette & backfill with cyanoacrylate. {1011}
    • Isobutyl acrylate is hydrolysed more slowly and hence is less toxic to the surronding tissue
    • cyanoacrylate is apparently biodegradable.
  • Durable, stable: one electrode displayed a single cortical spike (though not necessarily the same one) for more than 90 consecutive days.
  • unacceptably low impedance = 100K or less
  • Unit activity was present only 10-24H after surgery.
  • formal review of even older microelectrode studies.
  • 10nA should be 100x too small to have any effect on a platinum tip [17]
  • A seperable cell with a SNR of 3:1 would become lost if the electrode tip moved 15um away from a 20um soma.
    • "It becomes clear that the problem of holding single units for prolonged periods in the unrestrained animal is not achieved without considerable difficulty". Yet they think they have solved it.

____References____

Salcman, Michael and Bak, Martin J. Design, Fabrication, and In Vivo Behavior of Chronic Recording Intracortical Microelectrodes Biomedical Engineering, IEEE Transactions on BME-20 4 253 -260 (1973)

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ref: -0 tags: robinson pasquali carbon nanotube fiber fluidic injection dextran neural electrode date: 12-28-2017 04:20 gmt revision:0 [head]

PMID-29220192 Fluidic Microactuation of Flexible Electrodes for Neural Recording.

  • Use viscous dextran solution + PDMS channel system
  • Durotomy (of course)
  • Parylene-C insulated carbon fiber electrodes, cut with FIB or razor blade
  • Used silver ink to electrically / mechanically attach for recordings.
  • Tested in hydra, rat brain slice (reticular formation of thalamus), and in-vivo rat.
  • Electrodes, at 12um diameter, E=120GPa, are approximately 127x stiffer than one 4x20um PI (E=9GPa) probe. Less damage though.

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ref: -0 tags: Lieber nanoFET review silicon neural recording intracellular date: 12-28-2017 04:04 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

PMID-23451719 Synthetic Nanoelectronic Probes for Biological Cells and Tissue

  • Review of nanowireFETS for biological sensing
  • Silicon nanowires can be grown via vapor-liquid-solid or vapor-solid-solid, 1D catalyzed growth, usually with a Au nanoparticle.
  • Interestingly, kinks can be introduced via "iterative control over nucleation and growth", 'allowing the synthesis of complex 2D and 3D structures akin to organic chemistry"
    • Doping can similarly be introduced in highly localized areas.
    • This bottom-up synthesis is adaptable to flexible and organic substrates.
  • Initial tests used polylysine patterning to encourage axonal and dendritic growth across a nanoFET.
    • Positively charged amino group interacts with negative surface charge phospholipid
    • Lieber's group coats their SU-8 electrodes in poly-d-lysine as well {1352}
  • Have tested multiple configurations of the nanowire FET, including kinked, one with a SiO2 nanopipette channel for integration with the cell membrane, and one where the cell-attached fluid membrane functions as the semiconductor; see figure 4.
    • Were able to show recordings as one of the electrodes was endovascularized.
  • It's not entirely clear how stable and scalable these are; Si and SiO2 gradually dissolve in physiological fluid, and no mention was made of longevity.

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ref: Gilgunn-2012 tags: kozai neural recording electrodes compliant parylene flexible dissolve date: 12-28-2017 03:50 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

IEEE-6170092 (pdf) An ultra-compliant, scalable neural probe with molded biodissolvable delivery vehicle

    • Optical coherence tomography is cool.
  • Large footprint - 150 or 300um, 135um thick (13500 or 40500 um^2; c.f. tungsten needle 1963 (50um) or 490 (25um) um^2.)
  • Delivery vehicle is fabricated from biodissolvable carboxy-methylcellulose (CMC).
    • Device dissolves within three minutes of implantation.
    • Yet stiff enough to penetrate the dura of rats (with what degree of dimpling?)
    • Lithographic patterning process pretty clever, actually.
    • Parylene-X is ~ 1.1 um thick.
    • 500nm Pt is patterned via ion milling with a photoresist mask.
    • Use thin 20nm Cr etch mask for both DRIE (STS ICP) and parylene etch.
  • Probes are tiny -- 10um wide, 2.7um thick, coated in parylene-X.
  • CMC polymer tends to bend and warp due to stress -- must be clamped in a special jig.
  • No histology. Follow-up: {1399}

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ref: -0 tags: optogenetics micro LED flexible electrodes PET rogers date: 12-28-2017 03:24 gmt revision:9 [8] [7] [6] [5] [4] [3] [head]

PMID-23580530 Injectable, cellular-scale optoelectronics with applications for wireless optogenetics.

  • Supplementary materials
  • 21 authors, University Illinois at Urbana-Champaign, Tufts, China, Northwestern, Miami ..
  • GaN blue and green LEDs fabricated on a flexible substrate with stiff inserter.
    • Inserter is released in 15 min with a dissolving silk fibrin.
    • made of 250um thick SU-8 epoxy, reverse photocured on a glass slide.
  • GaN LEDS fabricated on a sapphire substrate & transfer printed via modified Karl-Suss mask aligner.
    • See supplemental materials for the intricate steps.
    • LEDs are 50um x 50um x 6.75um
  • Have integrated:
    • Temperature sensor (Pt serpentine resistor) / heater.
    • inorganic photodetector (IPD)
      • ultrathin silicon photodiode 1.25um thick, 200 x 200um^2, made on a SOI wafer
    • Pt extracellular recording electrode.
        • This insulated via 2um thick more SU-8.
  • Layers are precisely aligned and assembled via 500nm layer of epoxy.
    • Layers made of 6um or 2.5um thick mylar (polyethylene terephthalate (PET))
    • Layers joined with SU-8.
    • Wiring patterned via lift-off.
  • Powered via RF scavenging at 910 Mhz.
    • appeared to be simple, power in = light out; no data connection.
  • Tested vs control and fiber optic stimulation, staining for:
    • Tyrosine hydroxylase (makes l-DOPA)
    • c-fos, a neural activity marker
    • u-LEDs show significant activation.
  • Also tested for GFAP (astrocytes) and Iba1 (activated microglia); flexible & smaller devices had lower gliosis.
  • Next tested for behavior using a self-stimulation protocol; mice learned to self-stimulate to release DA.
  • Devices are somewhat reliable to 250 days!

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ref: -0 tags: kozai CMC dissolving insertion shuttle parylene date: 12-28-2017 03:19 gmt revision:1 [0] [head]

PMID-25128375 Chronic tissue response to carboxymethyl cellulose based dissolvable insertion needle for ultra-small neural probes.

  • CMC = carboxymethyl cellulose, commonly used as a food additive, in toothpaste, etc.
  • To address CMC dissolution, we developed a sophisticated targeting, high speed insertion (∼80 mm/s), and release system to implant shuttles.
  • Cross section of the probes are large, 300 x 125um and 100 x 125um.
  • Beautiful histology: the wound does gradually close up as the CMC dissolves, but no e-phys.

{1057}
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ref: Kozai-2009.11 tags: electrodes insertion Kozai flexible polymer momolayer date: 12-28-2017 02:59 gmt revision:12 [11] [10] [9] [8] [7] [6] [head]

PMID-19666051[0] Insertion shuttle with carboxyl terminated self-assembled monolayer coatings for implanting flexible polymer neural probes in the brain.

  • This study investigated the use of an electronegative (hydrophillic) self-assembled monolayer (SAM) as a coating on a stiff insertion shuttle to carry a polymer probe into the cerebral cortex, and then the detachment of the shuttle from the probe by altering the shuttle's hydrophobicity.
    • Used 11-mercaptoundecanoic acid.
    • Cr/Au (of course) evaporated on 15um thick Si shuttle.
    • SAM attracts water once inserted, causing the hydrophobic polymer to move away.
      • Why not make the polymer hydrophillic?
      • Is this just soap?
  • Used agarose brain model.
  • Good list of references for the justification of soft electrodes, and researched means for addressing this, mostly usnig polymer stiffeners.
    • "Computer models and experimental studies of the probe–tissue interface suggest that flexible and soft probes that approach the brain’s bulk material characteristics may help to minimize micromotion between the probe and surrounding tissue ({737}; {1203}; {1102}; {1200}; LaPlaca et al., 2005; {1216}; Neary et al., 2003 PMID-12657694; {1198})"
  • "However, polymer probes stick to metallic and silicon surfaces through hydrophobic interactions, causing the polymer probe to be carried out of the brain when the insertion shuttle is removed. The solution is to use a highly hydrophillic, electronegative, self-assembled monolayer coating on the shuttle.
  • Biran et al 2005 suggests that incremental damage due to stab wounds from the shuttle (needle) should be minor.
  • Probes: 12.5 um thick, 196 um wide, and 1.2cm long, polymide substrate and custom designed lithographed PDMS probes.
  • Polymer probes were inserted deep - 8.5 mm.
  • PDMS probes inserted with non-coated insertion shuttle resulted in explantation of the PDMS probe.

____References____

[0] Kozai TD, Kipke DR, Insertion shuttle with carboxyl terminated self-assembled monolayer coatings for implanting flexible polymer neural probes in the brain.J Neurosci Methods 184:2, 199-205 (2009 Nov 15)

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ref: -0 tags: platinum parylene electrodes brush dissolving stiffener gelatin date: 12-28-2017 02:44 gmt revision:0 [head]

PMID-27159159 Embedded Ultrathin Cluster Electrodes for Long-Term Recordings in Deep Brain Centers.

  • 12.5um pure Pt wires
  • Coated in 4um parylene-C
  • stiffened with gelatin
  • further protected with Kollicoat to retard dissolution.
  • Used a pulsed UV laser to ablate parylene, cut the platinum, and roughen the recording site.
  • See also {311}

{1397}
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ref: -0 tags: polyimide electrodes immune response foreign body inflammation stiffener steiglitz date: 12-28-2017 02:37 gmt revision:0 [head]

PMID-27534649 Intracortical polyimide electrodes with a bioresorbable coating.

  • Molten saccharose was used as coating material.
  • 270 x 10um polyimide recording probes. (large!)
  • Tissue reaction seems to peak at 2 weeks-4weeks, and decline somewhere thereafter. (though there were not a great number of samples.)

{1396}
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ref: -0 tags: rogers thermal oxide barrier neural implants ECoG coating accelerated lifetime test date: 12-28-2017 02:29 gmt revision:0 [head]

PMID-27791052 Ultrathin, transferred layers of thermally grown silicon dioxide as biofluid barriers for biointegrated flexible electronic systems

  • Thermal oxide proved the superior -- by far -- water barrier for encapsulation.
    • What about the edges?
  • Many of the polymer barrier layers look like inward-rectifiers:
  • Extensive simulations showing that the failure mode is from gradual dissolution of the SiO2 -> Si(OH)4.
    • Even then a 100nm layer is expected to last years.
    • Perhaps the same principle could be applied with barrier metals. Anodization or thermal oxidation to create a thick, nonporous passivation layer.
    • Should be possible with Al, Ta...

{1395}
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ref: -0 tags: Courtine e-dura PDMS silicone gold platinum composite stretch locomotion restoration rats date: 12-22-2017 01:59 gmt revision:0 [head]

PMID-25574019 Biomaterials. Electronic dura mater for long-term multimodal neural interfaces.

  • Fabrication:
    • 120um total PDMS thickness, made through soft lithography, covalent (O2 plasma) bonding between layers
    • 35nm of Au (thin!) deposited through a stencil mask.
    • 300um Pt-PDMS composite for electrode sites, deposited via screenprinting
  • 100 x 200um cross section drug delivery channel.
  • Compared vs. stiff 25um thick PI film electrode.
    • stiff implants showed motor impairments 1-2 weeks after implantation.
  • Showed remarkable recovery of supported locomotion with stimulation and drug infusion (to be followed by monkeys).

{1394}
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ref: -0 tags: Courtine PDMS soft biomaterials spinal cord e-dura date: 12-22-2017 01:29 gmt revision:0 [head]

Materials and technologies for soft implantable neuroprostheses

  • Quote: In humans, both the spinal cord and its meningeal protective membranes can experience as much as 10–20% tensile strain and
displacement (relative to the spinal canal) during normal postural movements. This motion corresponds to displacements on the order of centimetres17. The deformations relative to the spinal cord in animal models, such as rodents or non-human primates, are likely to be even larger.

{1393}
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ref: -2001 tags: polyimide Kipke bioactive flexible electrode arrays date: 12-22-2017 01:16 gmt revision:2 [1] [0] [head]

PMID-11327505 Flexible polyimide-based intracortical electrode arrays with bioactive capability.

  • Appears to be the first or one of the first use of thin-film polyimide for intracortical recording; will have to cite.
  • Fab protocol: 500nm release thermal oxide, photo-paternable PI, Cr-Au metalization, O2 plasma de-scum for adhesion (ish?), <20um total thickness.
  • Conductive epoxy attachment to connector.

{1392}
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ref: -0 tags: lieber mesh electronics SU-8 recording electrodes flexible polymer glass capillary date: 12-22-2017 00:14 gmt revision:0 [head]

PMID-29109247 Highly scalable multichannel mesh electronics for stable chronic brain electrophysiology

  • Key change was the addition of multiple conductor traces per longitudinal mesh line; this allows them to get 64 or 128 channels per mesh without a dramatic increase in modulus.
  • The latitudinal / diagonal lines still displace tissue ...
  • And the injection mechanism, glass pipette, 650um OD, 400um ID, is pretty large, even for 128 channels.
  • Use carbon nanotube ink, custom CNC printer, to connect to FPC.
    • Pretty impressive that they can manipulate ~800nm thick Su-8 film intraop and have it work well!

{1391}
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ref: -0 tags: computational biology evolution metabolic networks andreas wagner genotype phenotype network date: 06-12-2017 19:35 gmt revision:1 [0] [head]

Evolutionary Plasticity and Innovations in Complex Metabolic Reaction Networks

  • ‘’João F. Matias Rodrigues, Andreas Wagner ‘’
  • Our observations suggest that the robustness of the Escherichia coli metabolic network to mutations is typical of networks with the same phenotype.
  • We demonstrate that networks with the same phenotype form large sets that can be traversed through single mutations, and that single mutations of different genotypes with the same phenotype can yield very different novel phenotypes
  • Entirely computational study.
    • Examines what is possible given known metabolic building-blocks.
  • Methodology: collated a list of all metabolic reactions in E. Coli (726 reactions, excluding 205 transport reactions) out of 5870 possible reactions.
    • Then ran random-walk mutation experiments to see where the genotype + phenotype could move. Each point in the genotype had to be viable on either a rich (many carbon source) or minimal (glucose) growth medium.
    • Viability was determined by Flux-balance analysis (FBA).
      • In our work we use a set of biochemical precursors from E. coli 47-49 as the set of required compounds a network needs to synthesize, ‘’’by using linear programming to optimize the flux through a specific objective function’’’, in this case the reaction representing the production of biomass precursors we are able to know if a specific metabolic network is able to synthesize the precursors or not.
      • Used Coin-OR and Ilog to optimize the metabolic concentrations (I think?) per given network.
    • This included the ability to synthesize all required precursor biomolecules; see supplementary information.
    • ‘’’“Viable” is highly permissive -- non-zero biomolecule concentration using FBA and linear programming. ‘’’
    • Genomic distances = hamming distance between binary vectors, where 1 = enzyme / reaction possible; 0 = mutated off; 0 = identical genotype, 1 = completely different genotype.
  • Between pairs of viable genetic-metabolic networks, only a minority (30 - 40%) of reactions are essential,
    • Which naturally increases with increasing carbon source diversity:
    • When they go back an examine networks that can sustain life on any of (up to) 60 carbon sources, and again measure the distance from the original E. Coli genome, they find this added robustness does not significantly constrain network architecture.

Summary thoughts: This is a highly interesting study, insofar that the authors show substantial support for their hypotheses that phenotypes can be explored through random-walk non-lethal mutations of the genotype, and this is somewhat invariant to the source of carbon for known biochemical reactions. What gives me pause is the use of linear programming / optimization when setting the relative concentrations of biomolecules, and the permissive criteria for accepting these networks; real life (I would imagine) is far more constrained. Relative and absolute concentrations matter.

Still, the study does reflect some robustness. I suggest that a good control would be to ‘fuzz’ the list of available reactions based on statistical criteria, and see if the results still hold. Then, go back and make the reactions un-biological or less networked, and see if this destroys the measured degrees of robustness.

{1389}
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ref: -0 tags: photoacoustic tomography mouse imaging q-switched laser date: 05-11-2017 05:23 gmt revision:1 [0] [head]

Single-impulse panoramic photoacoustic computed tomography of small-animal whole-body dynamics at high spatiotemporal resolution

  • Used Q-switched Nd:YAG and Ti:Sapphire lasers to illuminate mice axially (from the top, through a diffuser and conical lens), exciting the photoacuostic effect, from which they were able to image at 125um resolution a full slice of the mouse.
    • I'm surprised at their mode of illumination -- how do they eliminate the out-of-plane photoacoustic effect?
  • Images look low contrast, but structures, e.g. cortical vasculature, are visible.
  • Can image at the rep rate of the laser (50 Hz), and thereby record cardiac and pulmonary rhythms.
  • Suggest that the photoacoustic effect can be used to image brain activity, but spatial and temporal resolution are limited.

{1390}
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ref: -0 tags: photoacoustic tomography mouse imaging q-switched laser date: 05-11-2017 05:21 gmt revision:0 [head]

Single-impulse panoramic photoacoustic computed tomography of small-animal whole-body dynamics at high spatiotemporal resolution

  • Used Q-switched Nd:YAG and Ti:Sapphire lasers to illuminate mice axially, exciting the photoacuostic effect, from which they were able to image at 125um resolution a full slice of the mouse.
  • Images look low contrast, but structures, e.g. cortical vasculature, are visible.
  • Can image at the rep rate of the laser (50 Hz), and thereby record cardiac and pulmonary rhythms.
  • Suggest that the photoacoustic effect can be used to image brain activity, but spatial and temporal resolution are limited.

{1239}
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ref: -0 tags: electrode area review impedance date: 04-28-2017 17:55 gmt revision:9 [8] [7] [6] [5] [4] [3] [head]

Quick review of electrode area / impedance within m8ta:

  • {895} 500um^2
  • {311} 490um^2 nominal; 900k
  • {1040} 108um^2, plated from 5M to 1M.
  • Neuronexus: 177, 413um, 700um, and 1250um.
    • Suggest 177um for SUA, 413um for MUA.
    • Community consensus seems to be that these electrodes don't last as long, though.
    • Electroplating 177um^2 sites with PEDOT:PSS reduces impedance to 23k {1388}
  • {823} 122um^2 nominal
  • {736} 500um^2
  • {1027} (Utah) 1600um^2
    • Impedance: ~ 220K +-91K (in vivo -- large variance)
    • Blackrock site lists impedance @ 400k
  • SIrOF Utah array -- 3100um^2 (3.1e-5cm^2) -- large!
    • Impedance ~50K according to [www.blackrockmicro.com/userfiles/file/Microelectrode%20Arrays.pdf Blackrock product brochure].
  • PMID-20124668 (Utah again) 2000um^2, 125k Pt, 6k SIROF.
  • Neuropixel: 144um^2 acid-etched TiN
  • Carbon fiber: ~38 um^2, PEDOT:PSS or PEDOT:pTS started ~ 4M, plated down to ~ 130k initial, went up to 2M pSS, 840k pTS.

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ref: -2016 tags: Kozai carbon fiber microelectrodes JNE PEDOT PSS pTS date: 04-27-2017 01:42 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

PMID-27705958 Chronic in vivo stability assessment of carbon fiber microelectrode arrays.

  • showed excellent recording characteristics and nearly zero glial scarring.
  • 6.4um carbon fiber + 800nm parylene-C = 8.4um.
    • Cytec Thoronel T-650 CF, Youngs modulus = 255 GPa, tensile strength = 4.28 GPa, PAN-based.
  • Everything protected with our wonderful phenol epoxy 353NDT, heat-cure.
  • Used two coating solutions:
    • Solution of 0.01 M 3,4-ethylenedioxythiophene (483028, Sigma-Aldrich, St. Louis, MO): 0.1 M sodium p-toluenesulfonate (152536, Sigma-Aldrich, St. Louis, MO).
      • pTS is not that dissimilar from it's alkyl cousin, SPS, {1353}. Likely a soapy chemical due to the opposed methyl and sulfonic acid group; benzine will take up less room in the polymer c.f. SDS & may lower the oxidation potential of EDOT.
      • Tosylates have been explored as a EDOT counterion : PMID-22383043 Characterization of poly(3,4-ethylenedioxythiophene):tosylate conductive polymer microelectrodes for transmitter detection. and PEDOT-TMA
    • Solution was composed of 0.01 M 3,4-ethylene-dioxythiophene (483028, Sigma-Aldrich, St. Louis, MO):0.1 M polystyrene sulfonate (m.w. 70.000, 222271000, Acros, NJ).
    • For each solution the electrodeposition was carried out by applying 100 pA/channel for 600 s to form a layer of poly(3,4-ethylenedioxythiophene):sodium p-toluenesulfonate (PEDOT:pTS) or poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS).
      • Weird, would use voltage control here..
  • According to works by Green et al [45] and Hukins et al [46], equation (1) can be used to determine the aging time that
the fibers have undergone: t 37=t TQ10 T37)/10 where t 37 is the simulated aging time at 37 °C, t T is the amount of real time that the samples have been kept at the elevated temperature, T , and Q10 is an aging factor that is equal to 2, according to ASTM guidelines for polymer aging [47].
  • Show > 2MOhm impedance of the small-area electrodes. At the aging endpoint, PEDOT:pTS had about half the impedance of PEDOT:PSS.
    • 4M PSS, 7M pTS, both plated down to ~ 130k initial, went up to 2M pSS, 840k pTS.
  • Recording capability quite stellar
  • Likewise for the glial response.

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ref: -0 tags: PEDOT PSS electroplate eletrodeposition neural recording michigan probe stimulation CSC date: 04-27-2017 01:36 gmt revision:1 [0] [head]

PMID-19543541 Poly(3,4-ethylenedioxythiophene) as a micro-neural interface material for electrostimulation

  • 23k on a 177um^2 site.
  • demonstrated in-vitro durable stimulation.
  • Electrodeposited with 6na for 900 seconds per electrode.
    • Which is high -- c.f. 100pA for 600 seconds {1356}
  • Greater CSC and lower impedance / phase than (comparable?) Ir or IrOx plating.

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ref: -1977 tags: polyethylene surface treatment plasma electron irradiation mechanical testing saline seawater accelerated lifetime date: 04-15-2017 06:06 gmt revision:0 [head]

Enhancement of resistance of polyethylene to seawater-promoted degradation by surface modification

  • Polyethylene, when repeatedly stressed and exposed to seawater (e.g. ships' ropes), undergoes mechanical and chemical degradation.
  • Surface treatments of the polyethlyene can improve resistance to this degradation.
  • The author studied two methods of surface treatment:
    • Plasma (glow discharge, air) followed by diacid (adipic acid) or triisocyanate (DM100, = ?) co-polymerization
    • Electron irradiation with 500 kEV electrons.
  • Also mention CASING (crosslinking by activated species of inert gasses) as a popular method of surface treatment.
    • Diffuse-in crosslinkers is a third, popular these days ...
    • Others diffuse in at temperature e.g. a fatty acid - derived molecule, which is then bonded to e.g. heparin to reduce the thrombogenicity of a plastic.
  • Measured surface modifications via ATR IR (attenuated total reflectance, IR) and ESCA (aka XPS)
    • Expected results, carbonyl following the air glow discharge ...
  • Results:
    • Triisocyanate, ~ 6x improvement
    • diacid, ~ 50 x improvement.
    • electron irradiation, no apparent degradation!
      • Author's opinion that this is due to carbon-carbon crosslink leading to mechanical toughening (hmm, evidence?)
  • Quote: since the PE formulation studied here was low-weight, it was expected to lose crystallinity upon cyclic flexing; high density PE's have in fact been observed to become more crystalline with working.
    • Very interesting, kinda like copper. This could definitely be put to good use.
  • Low density polyethylene has greater chain branching and entanglement than high-density resins; when stressed the crystallites are diminished in total bulk, degrading tensile properties ... for high-density resins, mechanical working loosens up the structure enough to allow new crystallization to exceed stress-induced shrinkage of crystallites; hence, the crystallinity increases.

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ref: -0 tags: tungsten eletropolishing hydroxide cleaning bath tartarate date: 03-28-2017 16:34 gmt revision:0 [head]

Method of electropolishing tungsten wire US 3287238 A

  • The bath is formed of 15% by weight sodium hydroxide, 30% by weight sodium potassium tartrate, and 55% by weight distilled water, with the bath temperature being between 70 and 100 F.
    • If the concentration of either the hydroxide or the tartrate is below the indicated minimum, the wire is electrocleaned rather than electropolished, and a matte finish is obtained rather than a specular surface.
    • If the concentration of either the hydroxide or the tartrate is greater than the indicated maximum, the electropolishing process is quite slow.
  • The voltage which is applied between the two electrodes 18 and 20 is from 16 to 18.5 volts, the current through the bath is 20 to 24 amperes, and the current density is 3,000 to 4,000 amperes per square foot of surface of wire in the bath.

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ref: -0 tags: polyimide electrodes thermosonic bonding Stieglitz adhesion delamination date: 03-06-2017 21:58 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

IEEE-6347149 (pdf) Improved polyimide thin-film electrodes for neural implants 2012

  • Tested adhesion to Pt / SiC using accelerated aging in saline solution.
  • Targeted at retinal prostheses.
  • Layer stack:
    • 50nm SiC deposited through PECVD @ 100C using SPS, with low frequency RF modulation.
    • 100nm Pt
    • 100nm Au
    • 100nm Pt
      • These layers will alloy during cure, and hence reduce stress.
    • 30nm SiC
    • 10nm DLC (not needed, imho; PI sticks exceptionally well to clean SiC)
  • Recent studies have concluded that adhesion to PI is through carbon bindings and not through oxide formation.
    • Adhesion of polyimide to amorphous diamond-like carbon and SiC deteriorates at a minimal rate.
  • Delamination is caused by residual stress, which is not only inevetable but a major driving force for cracking in thin films.
    • Different CTE in layer stack -> different contraction when cooling from process temperature.
  • Platinum, which evaporates at 1770C, and is deposited ~100C (photoresists only withstand ~115C) results in a high-stress interface.
    • Pt - Carbon bonds only occur above 1000C
  • After 9 and 13 days of incubation the probes with 400 nm and 300nm of SiC, respectively, which were not tempered, showed complete delamination of the Pt from the SiC.
    • 60C, 0.9 M NaCl, 1 year.
    • The SiC remained attached to the PI.
      • Tempering: repeated treatment at 450C for 15 min in a N2 atmosphere.
    • All other probes remained stable.
  • Notably, used thermosonic bonding to the PI films, using sputtered (seed layer) then 12um electroplated Au.
  • Also: fully cured the base layer PI film.
  • Used oxygen plasma de-scum after patterning with resists to get better SiC adhesion to PI.
    • And better inter-layer adhesion (fully cured the first polyimide layer @ 450C).
  • Conclusion: "The fact that none of the tempered samples delaminated even after ~5 years of lifetime (extrapolated for 37 C) shows a tremendous increase in adhesion.

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ref: Seymour-2007.09 tags: neural probe design recording Kipke Seymour parelene MEA histology PEDOT date: 02-23-2017 23:52 gmt revision:13 [12] [11] [10] [9] [8] [7] [head]

PMID-17517431[0] Neural probe design for reduced tissue encapsulation in CNS.

  • See conference proceedings too: PMID-17947102[1] Fabrication of polymer neural probes with sub-cellular features for reduced tissue encapsulation.
    • -- useful information.
  • They use SU8 - photoresist! - as a structural material. See also this.
    • They use silicon as a substrate for the fabrication, but ultimately remove it. Electrodes could be made of titanium, modulo low conductivity.
  • Did not / could not record from these devices. Only immunochemistry.
  • Polymer fibers smaller than 7um are basically invisible to the immune system. See [2]
  • Their peripheral recording site is 4 x 5um - but still not invisible to microglia. Perhaps this is because of residual insertion trauma, or movement trauma? They implanted the device flush with the cortical surface, so there should have been little cranial tethering.
  • Checked the animals 4 weeks after implantation.
  • Peripheral electrode site was better than shank location, but still not perfect. Well, any improvement is a good one...
  • No statistical difference between 4x5um lattice probes, 10x4um probes, 30x4um, and solid (100um) knife edge.
    • Think that this may be because of electrode micromotion -- the lateral edge sites are still relatively well connected to the thick, rigid shank.
  • Observed two classes of immune reactivity --
    • GFAP reactive hypertrophied astrocytes.
    • devoid of GFAP, neurofilament, and NEuN, but always OX-42 and often firbronectin and laminin positive as well.
    • Think that the second may be from meningeal cells pulled in with the stab wound.
  • Sensitivity is expected to increase with decreased surface area (but similar low impedance -- platinum black or oxidized iridium or PEDOT {1112} ).
  • Thoughts: it may be possible to put 'barbs' to relieve mechanical stress slightly after the probe location, preferably spikes that expand after implantation.
  • His thesis {1110}

____References____

[0] Seymour JP, Kipke DR, Neural probe design for reduced tissue encapsulation in CNS.Biomaterials 28:25, 3594-607 (2007 Sep)
[1] Seymour JP, Kipke DR, Fabrication of polymer neural probes with sub-cellular features for reduced tissue encapsulation.Conf Proc IEEE Eng Med Biol Soc 1no Issue 4606-9 (2006)
[2] Sanders JE, Stiles CE, Hayes CL, Tissue response to single-polymer fibers of varying diameters: evaluation of fibrous encapsulation and macrophage density.J Biomed Mater Res 52:1, 231-7 (2000 Oct)

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ref: Schmidt-1993.11 tags: Normann utah array histology silicon electrode array cats date: 02-23-2017 22:03 gmt revision:4 [3] [2] [1] [0] [head]

PMID-8263001[0] Biocompatibility of silicon-based electrode arrays implanted in feline cortical tissue.

  • Tried two different times:
    • one day before euthanasia
    • 6 month implant.
  • Tried three different implants:
    • Uncoated silicon,
    • polymide coating
    • polymide coating with SiO2 adhesion layer / primer.
  • The last was the worst in terms of histopathological response.
  • Chronic implants showed relatively restrained immune response,
    • Gliosis was found around all tracks, 20-40um.
  • Encapsulation was less than 9um.
  • Edema and hemorrhage was minor but present on a subset of all implants.
  • Acute (24h) hemorrhage was more severe -- ~ 60%; edema ~ 20%.
  • Chronic histology revealed considerable macrophages w/ hemosiderin (a complex including ferritin)
  • See also [1]

____References____

[0] Schmidt S, Horch K, Normann R, Biocompatibility of silicon-based electrode arrays implanted in feline cortical tissue.J Biomed Mater Res 27:11, 1393-9 (1993 Nov)
[1] Jones KE, Campbell PK, Normann RA, A glass/silicon composite intracortical electrode array.Ann Biomed Eng 20:4, 423-37 (1992)

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ref: -0 tags: carbon nanotube densification conductivity strength date: 02-23-2017 02:52 gmt revision:2 [1] [0] [head]

Super-strong and highly conductive carbon nanotube ribbons from post-treatment methods

  • Conductivity of 1.2e6 S/m, about that of stainless steel.
    • 500 x 500nm wire, length 1cm will have a resistance of 40k.
  • Aerogel method: methane + ferrocene + thiophene + hydrogen.
    • Resulting in ~ 18% Fe, multi-walled carbon nanotubes, diameter 15nm, 15-20 walls.
  • Densified with a stainless-steel spatula on regular paper.
    • Resulting in ribbons 22um wide, 650nm thick.
  • Very high tensile strength, up to 5.2 GPa; moduls ~ 266 GPa.

High-strength carbon nanotube fibre-like ribbon with high ductility and high electrical conductivity

  • Slightly higher conductivity, 1.82 - 2.24e6 S/m.
  • Rolled until it was 500nm thick!
  • Spun from an aerogel (!!) using ethanol + ferrocent + thiophene.

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ref: -0 tags: iridium oxide nanotube intracellular recording electroplate MEA date: 02-22-2017 22:41 gmt revision:0 [head]

PMID-24487777 Iridium oxide nanotube electrodes for sensitive and prolonged intracellular measurement of action potentials.

  • Electrodeposition of IrOx "magically" forms 500nm tubes.
  • Holes in Si3N4 / SiO2 were formed via e-beam lithography; underlying Pt wires via liftoff.
  • Showed long (minutes) intracellular access, though it tended to dip with time.

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ref: -0 tags: glassy carbon SU-8 pyrolysis CEC microelectrode stimulation stability platinum PEDOT date: 02-17-2017 00:05 gmt revision:2 [1] [0] [head]

A novel pattern transfer technique for mounting glassy carbon microelectrodes on polymeric flexible substrates

  • Use inert-atmosphere pyrolysis @ 900 - 1000 C of 20um SU-8 (which is aromatic) on a thermal oxide wafer.
  • Followed by spin & cure of PI.
  • Demonstrate strong carbonyl bonding of the glassy carbon with mechanical and FTIR testing.
  • Use of photosensitive PI allows through-vias to connect Cr/Au conductive traces.

PMID-28084398 Highly Stable Glassy Carbon Interfaces for Long-Term Neural Stimulation and Low-Noise Recording of Brain Activity

  • Use EIS to show superior charge-injection properties + stability of glassy carbon electrodes vs. Pt electrodes.
    • GC lasted > 5e6 pulses; Pt electrodes delaminated after 1e6 pulses.
    • Hydrogen bonding (above) clearly superior than neat PI-Pt interface
  • GC electrodes were, true to their name, glassy and much smoother than the platinum electrodes.
  • Further reduced impedance with PEDOT-PSS coating.
    • PEDOT-PSS coating on glassy carbon was, in their hands, far more stable than PEDOT-PSS on platinum.
  • All devices, GC, PEDOT:PSS, and Pt, had similar biocompatibility in their assay (figure 7)

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ref: -0 tags: myoelectric EMG recording TMR prosthetics date: 02-13-2017 20:43 gmt revision:0 [head]

PMID: Man/machine interface based on the discharge timings of spinal motor neurons after targeted muscle reinnervation

  • General idea: deconvolve a grid-recorded EMG signal to infer the spinal motorneron spikes, and use this to more accurately decode user intention.
  • EMG envelope is still fairly good...

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ref: -0 tags: polypyrrole date: 02-09-2017 01:26 gmt revision:0 [head]

PMID-23307738 Bio-inspired Polymer Composite Actuator and Generator Driven by Water Gradients

  • Alas, water gradient driven, not electrically driven. Still, highly interesting ... check out the videos.

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ref: -0 tags: carbon fiber thread spinning Pasquali Kemere nanotube stimulation date: 02-09-2017 01:09 gmt revision:0 [head]

PMID-25803728 Neural stimulation and recording with bidirectional, soft carbon nanotube fiber microelectrodes.

  • Poulin et al. demonstrated that microelectrodes made solely of CNT fibers22 show remarkable electrochemical activity, sensitivity, and resistance to biofouling compared to conventional carbon fibers when used for bioanalyte detection in vitro.23-25
  • Fibers were insulated with 3 um of block copolymer polystyrene-polybutadiene (PS-b-PBD) (polybutadiene is sythetic rubber)
    • Selected for good properties of biocompatibility, flexibility, resistance to flextural fatigue.
    • Available from Sigma-Aldrich.
    • Custom continuous dip-coating process.
  • 18um diameter, 15 - 20 x lower impedance than equivalently size PtIr.
    • 2.5 - 6x lower than W.
    • In practice, 43um dia, 1450um^2, impedance of 11.2 k; 12.6um, 151k.
  • Charge storage capacity 327 mC / cm^2; PtIr = 1.2 mC/cm^2
  • Wide water window of -1.5V - 1.5V, consistent with noble electrochemical properties of C.
  • Lasts for over 97e6 pulsing cycles beyond the water window, vs 43e6 for PEDOT.
  • Tested via 6-OHDA model of PD disease vs. standard PtIr stimulating electrodes, implanted via 100um PI shuttled attached with PEG.
  • Yes, debatable...
  • Tested out to 3 weeks durability. Appear to function as well or better than metal electrodes.

PMID-23307737 Strong, light, multifunctional fibers of carbon nanotubes with ultrahigh conductivity.

  • Full process:
    1. Dissolve high-quality, 5um long CNT in chlorosulfonic acid (the only known solvent for CNTs)
    2. Filter to remove particles
    3. Extrude liquid crystal dope through a spinneret, 65 or 130um orifice
    4. Into a coagulant, acetone or water
    5. Onto a rotating drum to put tension on the thread & align the CNTs.
    6. Wash in water and dry at 115C.
  • Properties:
    • Tensile strength 1 GPa +- 0.2 GPa.
    • Tensile modulus 120 GPa +- 50, best value 200 GPa
      • Pt: 168 GPa ; Au: 79 GPa.
    • Elongation to break 1.4 %
    • Conductivity: 0.3 MS/m, Iodine doped 5 +- 0.5 MS/m (22 +- 4 microhm cm)
      • Cu: 59.6 MS/m ; Pt: 9.4 MS/m ; Au: 41 MS/m
      • Electrical conductivity drops after annealing @ 600C
      • But does not drop after kinking and repeated mechanical cycling.
  • Theoretical modulus of MWCNT ~ 350 GPa.
  • Fibers well-aligned at ~ 90% the density (measure 1.3 g/cc) of close-packed CNT.

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ref: -0 tags: nanoprobe transmembrane intracellular thiol gold AFM juxtacellular date: 02-06-2017 23:45 gmt revision:3 [2] [1] [0] [head]

PMID-20212151 Fusion of biomimetic stealth probes into lipid bilayer cores

  • Used e-beam evaporation of Cr/Au/Cr 10/10/10 or 10/5/10 onto a Si AFM tip.
    • Approx 200nm diameter; 1800 lipid interaction at the circumference.
  • Exposed the Au in the sandwich via FIB
  • Functionalized the Au with butanethiol or dodecanthiol; former is mobile on the surface, latter is polycrystaline.
    • Butanethiol showed higher adhesion to the synthetic membranes
  • Measured the penetration force & displacement through synthetic multi-layer lipid bilayers.
    • These were made via a custom protocol with 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine (SOPC) and cholesterol

PMID-21469728 '''Molecular Structure Influences the Stability of Membrane Penetrating Biointerfaces.

  • Surprisingly, hydrophobicity is found to be a secondary factor with monolayer crystallinity the major determinate of interface strength
  • Previous studies using ellipsometry and IR spectroscopy have shown that alkanethiol self-assembled monolayers display an abrupt transition from a fluid to a crystalline phase between hexanethiol and octanethiol.
    • This suggests the weakening of the membrane stealth probe interface is due to the crystallinity of the molecular surface with fluid, disordered monolayers promoting a high strength interface regime and rigid, crystalline SAMs forming weak interfaces.

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ref: -0 tags: nanopore membrane nanostraws melosh surface adhesion intracellular date: 02-06-2017 23:34 gmt revision:0 [head]

PMID-22166016 Nanostraws for Direct Fluidic Intracellular Access

  1. Used track-etched polycarbonate membranes, which have controlled pore density & ID.
  2. Deposited alumina on the pores & external surfaces using ALD
  3. Then etched away the top alumina
  4. and finally used O2 RIE to etch away the polycarbonate.
  • Show that these nanopores have cytosolic access (via Fluor 488 - hydrazide membrane impermeant dye
  • Also used nanostraws to deliver Co+2 to quench GFP fluorescence.

PMID-24710350, Quantification of nanowire penetration into living cells.

  • We discover that penetration is a rare event: 7.1±2.7% of the nanostraws penetrate the cell to provide cytosolic access for an extended period for an average of 10.7±5.8 penetrations per cell.
  • Using time-resolved delivery, the kinetics of the first penetration event are shown to be adhesion dependent and coincident with recruitment of focal adhesion-associated proteins.
    • Hours for unmodified, 5 minutes for adhesion-promoting surface.
  • Chinese hamster oviary cells expressing GFP, Co+2 quenching, EDTA chelation.
  • To modulate cell adhesion, nanostraw substrates were incubated in 10 μg ml−1 fibronectin, a well-characterized cell adhesion molecule, in addition to the standard polyornithine coating.

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ref: -0 tags: review neural recording penn state extensive biopolymers date: 02-06-2017 23:09 gmt revision:0 [head]

PMID-24677434 A Review of Organic and Inorganic Biomaterials for Neural Interfaces

  • Not necessarily insightful, but certainly exhaustive review of all the various problems and strategies for neural interfacing.
  • Some emphasis on graphene, conductive polymers, and biological surface treatments for reducing FBR.
  • Cites 467 articles!

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ref: -0 tags: intracellular juxtacellular recording tungsten nanowire whole cell patch date: 02-06-2017 22:39 gmt revision:2 [1] [0] [head]

PMID-22905231 Neuronal recordings with solid-conductor intracellular nanoelectrodes (SCINEs).

  • <300 nm diameter W fibers, several um long, fabricated via FIB.
  • Functionalized with a hydrophobic silane on the oxide.
    • Quite complete & custom methods here.
  • Not quite whole cell recording, but excellent SNR; 4mv APs.
    • Slice, rat hippocampus organotypic.
    • Expected much larger recorded APs; suspect partial membrane penetration.
    • Only lasted a few seconds to minutes.
  • Needed custom recording setup for interfacing with 100Gohm electrodes; stray capacitance < 4 pf.
  • Intracellular electrodes must be designed to not shunt the membrane open upon insertion.
    • In a study where whole-cell recordings were established prior sharp microelectrode penetration, all neurons showed significant depolarization following impalement.
    • Here there was no change in membrane voltage in 10% of insertions of the silane-functionalized SCINEs. only in the functionalized electrodes).
    • Minor distortion of the AP was observed.
  • In whole-cell patch clamping, diffusion from the pipette to the cytosol interrupts biochemical processes necessary for normal cellular function (e.g. respiration!).
  • The hardness of the tungsten ensures that SCINEs can be repeatedly inserted millimeter-deep into brain tissue without noticeable damage to the tip.
    • E.g. 300 nm tungsten will not easily navigate vasculature...

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ref: -0 tags: carbon fiber pitch based tensile strength date: 02-04-2017 00:07 gmt revision:4 [3] [2] [1] [0] [head]

Contenders for high-modulus pitch-based carbon fiber: "

CorpModelYoung's modulusTensile StrengthDiameter Elongation at break
Nippon Graphite Fiber CoGranoc XN-90860 GPa3.43 GPa10 um0.4%
Mitsubishi RayonK13D2U940 GPa3.21 GPa11 um0.36%
Cytec ThornelP-120830 GPa2.41 GPa??0.3-0.5%
Cytec ThornelK1100965 GPa3.10 GPa10 um??

Tensile and Flextural Prperties of single carbon fibers

  • High modulus pitch-based carbon fibers have quite low compressive and shear strengths. The flexural strength could be affected strongly by its low strength under compression and shear loading.

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ref: -0 tags: bone marrow transplant chimera immune response to indwelling electrode implant capadona inflammation date: 02-02-2017 23:24 gmt revision:1 [0] [head]

PMID-24973296 The roles of blood-derived macrophages and resident microglia in the neuroinflammatory response to implanted intracortical microelectrodes.

  • Quite good introductory review on current understanding of immune / inflammatory / BBB breakdown response to indwelling neural implants.
  • Used chimera mice with marrow from CFP mice transplanted into irradiated hosts, so myeloid cells were labeled (including macrophages and monocytes).
    • Details of this process are properly fascinating ... there are clever ways of isolating and selecting the right marrow cells.
  • Implanted with a dummy Michigan style probe, 2mm x 123 um x 15um.
  • Histological processes and cell sorting / labeling also highly detailed.
  • 60% of the infiltrating cells (CFP+) are macrophages.
    • Within the total IBA1+ population (macrophages + microglia), we saw that only 20% of the total IBA1+ population was comprised of microglia at two weeks post implantation (Fig. 9G).
    • Additionally, at chronic time points (four, eight and sixteen weeks), we observed that less than 40% of the total IBA1+ population was comprised of microglia (Fig. 9G).
    • On the other hand, no significant differences were observed in microglia populations over time (Fig. 9G, Table 4). Together, our results suggest a predominant role of infiltrating macrophages surrounding implanted microelectrodes over time.
  • IBA1 = marker for ionized calcium binding adapter molecule, to label the total population of microglia/ macrophages (both resting and activated)
  • CD68 = activated microglia / macrophage.
    • Hard to discriminate microglia and infiltrating macrophages.
  • Interestingly, fluctuations in GFAP+ immunoreactivity correlated well with neuronal density and CFP+ immunoreactivty, suggesting a possible role of astrocytes in facilitating trafficking of blood-derived cells.
  • Contrary to what has been suggested by many intracortical microelectrode studies, a consistent connection was not found between activated microglia/macrophages and neuron density in our chimera models

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ref: -0 tags: nanotube tracking extracellular space fluorescent date: 02-02-2017 22:13 gmt revision:0 [head]

PMID-27870840 Single-nanotube tracking reveals the nanoscale organization of the extracellular space in the live brain

  • Extracellular space (ECS) takes up nearly a quarter the volume of the brain (!!!)
  • Used the intrinsic fluorescence of single-walled carbon nanotubes @ 1um, 845nm excitation, with super-resolution tracking of diffusion.
    • Were coated in phospholipid-polyethylene glycol (PL-PEG), which display low cytotoxicity compared to other encapsulants.
  • 5ul, 3ug/ml injected into the ventricles of young rats; allowed to diffuse for 30 minutes post-injection.
  • No apparent response of the microglia.
  • Diffusion tracking revealed substantial dead-space domains in the ECS.
    • As compared to patch-clamp loaded SWCNTs
  • Estimate from parallel and perpendicular diffusion rates that the characteristic scale of ECS dimension is 80 to 270nm, or 150 +- 40nm.
  • The ECS nanoscale dimensions as visualized by tracking similar in dimension and tortuosity to electron microscopy.
  • Viscosity of the extracellular matrix from 1 to 50 mPa S, up to two orders of magnitude higher than the CSF.
  • Positive control through hyalurinase + several hours to digest the hyaluronic acid.
    • But no observed changes in morphology of the neurons via confocal .. interesting.
    • Enzyme digestion normalized the spatial heterogenaity of diffusion.

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ref: -0 tags: juxtacellular recording gold mushroom cultured hippocampal neurons Spira date: 02-01-2017 02:44 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

Large-Scale Juxtacellular Recordings from Cultured Hippocampal Neurons by an Array of Gold-Mushroom Shaped Microelectrodes

  • Micrometer sized Au mushroom MEA electrodes.
  • Functionalized by poly-ethylene-imine (PEI, positively charged)/laminin (extracellular matrix protein) undergo a process to form juxtacellular junctions between the neurons and the gMµEs.
  • No figures, but:
    • Whereas substrate integrated planar MEA record FPs dominated by negative-peak or biphasic-signals with amplitudes typically ranging between 40-100 µV and a signal to noise ratio of ≤ 5,
    • The gMµE-MEA recordings were dominated by positive monophasic action potentials.
    • It is important to note that monophasic high peak amplitudes ≥ 100 µV are rarely obtained using planar electrodes arrays, whereas when using the gMµE-MEA, 34.48 % of the gMµEs recorded potentials ≥ 200 µV and 10.64 % recorded potentials in the range of 300-5,085 µV.
  • So, there is a distribution of coupling, approximately 10% "good".

PMID-27256971 Multisite electrophysiological recordings by self-assembled loose-patch-like junctions between cultured hippocampal neurons and mushroom-shaped microelectrodes.

  • Note 300uV - 1mV extracellular 'juxtacellular' action potentials from these mushroom recordings. This is 2 - 5x better than microwire extacellular in-vivo ephys; coupling is imperfect.
    • Sharp glass-insulated W electrodes, ~ 10Mohm, might achieve better SNR if driven carefully.
  • 2um mushroom cap Au electrodes, 1um diameter 1um long shaft
    • No coating, other than the rough one left by electroplating process.
    • Impedance 10 - 25 Mohm.
  • APs decline within a burst of up to 35% -- electrostatic reasons?
  • Most electrodes record more than one neuron, similar to in-vivo ephys, with less LFP coupling.

PMID-23380931 Multi-electrode array technologies for neuroscience and cardiology

  • The key to the multi-electrode-array ‘in-cell recording’ approach developed by us is the outcome of three converging cell biological principals:
    • (a) the activation of endocytotic-like mechanisms in which cultured Aplysia neurons are induced to actively engulf gold mushroom-shaped microelectrodes (gMμE) that protrude from a flat substrate,
    • (b) the generation of high Rseal between the cell’s membrane and the engulfed gMμE, and
    • (c) the increased junctional membrane conductance.
  • Functionalized the Au mushrooms with an RGD-based peptide
    • RGD is an extracellular matrix binding site on fibronectin, which mediates it's interaction with integrin, a cell surface receptor; it is thought that other elements of fibronectin regulate specificity with its receptor. PMID-2418980

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ref: -0 tags: vertical nanowire juxtacellular recording date: 02-01-2017 00:50 gmt revision:2 [1] [0] [head]

PMID-22231664 Vertical nanowire electrode arrays as a scalable platform for intracellular interfacing to neuronal circuits.

  • Note actual coupling is low, 0.002, compared to patch-clamp (400uV vs 200mV). Signal is rather noisy.
  • Dissociated cultures of rat cortical neurons
  • Stimulation current 200 pa enough to change membrane potential, but not initiate a spike.
    • This is 200e-12 / 20e-6 = 5 orders of magnitude lower current than typical ICMS.

{1367}
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ref: -0 tags: microstimulation rat cortex measurement ICMS spread date: 01-26-2017 02:52 gmt revision:0 [head]

PMID-12878710 Spatiotemporal effects of microstimulation in rat neocortex: a parametric study using multielectrode recordings.

  • Measure using extracellular ephys a spread of ~ 1.3mm from near-threshold microstimulation.
  • Study seems thorough despite limited techniques.

{1366}
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ref: -0 tags: direct electrical stimulation neural mapping review date: 01-26-2017 02:28 gmt revision:0 [head]

PMID-22127300 Direct electrical stimulation of human cortex -- the gold standard for mapping brain functions?

  • Fairly straightforward review, shows the strengths and weaknesses / caveats of cortical surface stimulation.
  • Axon initial segment and nodes of Ranvier (which has a high concentration of Na channels) are the most excitable.
  • Stimulation of a site in the LGN of the thalamus increased the BOLD signal in the regions of V1 that received input from that site, but strongly suppressed it in the retinotopicaly matched regions of extrastriate cortex.
  • To test the hypothesis that the deactivation of extrastriate cortex might be due to synaptic inhibition of V1 projection neurons, GABA antagonists were microinjected into V1 in monkeys in experiments that combined fMRI, ephys, and microstim.
    • Ref 25. PMID-20818384
    • These findings suggest that the stimulation of cortical neurons disrupts the propagation of cortico-cortico signals after the first synapse.
    • Likely due to feedforward and recurrent inhibition.
  • Revisit the hypothesis of tight control of excitation and inhibition (e.g. in-vivo patch clamping + drugs). "The interactions between excitation and inhibition within cortical microcircuits as well as between inter-regional connections haper the predicability of stimulation."
  • The average size of a fMRI voxel:
    • 55ul, 55mm^2
    • 5.5e6 neurons,
    • 22 - 55e9 billion synapses,
    • 22km dendrites (??)
    • 220km axons.
  • In the 1970s, Daniel Pollen conducted a series of studies stimulating the visual cortex of cats and humans.
    • Observed long intra-stim responses, and post-stim afterdischarges.
    • Importantly, he also observed inhibitory effects of DES on cortical responses at the stimulation site.
      • The inhibitory effect depended on the state of the neuron before stimulation.
      • High spontaneous activity + low stim strengths = inhibition;
      • low spontaneous activity + high stim strengths = excitation.
  • In the author's opinion, there is an equal or greater number of inhibitory responses to electrical microstimulation as excitatory. Only, there is a reporting bias toward the positive.
  • Many locations for paresthesias:
    • postcentral sulcus (duh)
    • opercular area inferior postcentral gyrus (e.g. superior to and facing the temporal lobe)[60]
    • posterior cingulate gyrus
    • supramarginal gyrus
    • temporal lobe, limbic and isocortical structures.

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ref: -0 tags: Kleinfeld vasculature cortex review ischemia perfusion date: 01-22-2017 19:40 gmt revision:3 [2] [1] [0] [head]

PMID-25705966 Robust and fragile aspects of cortical blood flow in relation to the underlying angioarchitecture.

  • "The penetrating arterioles that connect the pial network to the subsurface network are bottlenecks to flow; occlusion of even a single penetrating arteriole results in the death of a 500 μm diameter cylinder of cortical tissue despite the potential for collateral flow through microvessels."
  • The pioneering work of Fox and Raichle [7] suggest that there is simply not enough blood to go around if all areas of the cortex were activated at once.
  • There is strong if only partially understood coupling between neuronal and vascular dysfunction [15]. In particular, vascular disease leads to neurological decline and diminished cognition and memory [16].
  • A single microliter of cortex holds nearly one meter of total vasculature length wow! PMID-23749145
  • Subsurface micro vasculature (not arterioles or venules) is relatively robust to occlusion; figure 4.

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ref: -0 tags: polyimide precursors date: 01-22-2017 06:03 gmt revision:1 [0] [head]

Dianhydride:

Dianiline / diamine:

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ref: -0 tags: polyimide aqueous degradation kapton date: 01-22-2017 05:51 gmt revision:0 [head]

Aqueous degradation of polyimides

  • Above ph 2, Kapton (PMDA-ODA) test specimens decreased both tensile strength and elongation to break with water, with a rate that increased with temperature.
  • No samples completely degraded, however; tensile strength decreased by about 2x, and elongation from 30% to 5%.
  • The authors suspect that ortho (off-molecular axis) amide bonding, at about 0.6% of the total number of imide bonds, is responsible for this (otherwise the film would completely fall apart.)
  • Imide bonds themselves are robust to all but strong bases and acids.
  • See also {1253}.

{1253}
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ref: -0 tags: polyimide stieglitz stability date: 01-22-2017 05:35 gmt revision:1 [0] [head]

PMID-20144477 In vitro evaluation of the long-term stability of polyimide as a material for neural implants

  • PI degrades at 85C in PBS; otherwise, it's stable.
  • mechanical tests only; no electrical tests.
  • Durimide 7510 contains a photo-initiator and an adhesion promoter. Spin-coatable.
    • Adhesion can be inhibited with C4F8
    • notably softer.
  • Dupont Kapton is PMDA-ODA (phenol linkage in the amide); PI-2611 is BPDA-PPD (aromatic carbon-carbon in the dicarboxcylic acid). The latter resists water uptake better.

{1305}
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ref: -0 tags: graphene polyimide polymerization date: 01-22-2017 05:20 gmt revision:3 [2] [1] [0] [head]

Preparation and properties of graphene oxide/polyimide composite films with low dielectric constant and ultrahigh strength via in situpolymerization

  • The GO/PI composite films provide ultrahigh tensile strength (up to 844 MPa) and Young's modulus (20.5 GPa).
    • Almost 10x increase in tensile strength!
    • And even larger increase in modulus.
  • Also, you can reduce graphene / graphite oxide with an infrared laser: http://pubs.acs.org/doi/abs/10.1021/nn204200w

{927}
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ref: Bartels-2008.09 tags: neurotrophic kennedy speech FM transmitter wireless Georga recording electrophysiology electrode date: 01-19-2017 02:18 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

PMID-18672003[0] Neurotrophic electrode: method of assembly and implantation into human motor speech cortex.

  • Glass electrode with 3-4 2mil Teflon insulated Au wires within it to record spiking.
  • Induce neurites (e.g. dendrites, axons, blood vessels, oligodendrocytes) to grow up into it using autologous sciatic nerve, and stay for the lifetime of the patient (Kennedy 1989) [1].
    • Histology has revealed axons, but not neurons, within the tissue inside the tip. (Kennedy 1989, 1992a.)
    • No glia in rat and monkey tests; PMID-1421115
    • Inserted 5-6mm into the cortex at an angle of 45 deg. far!?
  • Bipolar amplification on pairs of the Au wires.
  • patients damaged their electrodes due to spasms; same for monkeys, presumably. Seems the electronice and gold wires are also highly fragile. I'm quite familiar with this.
  • Includes a sine wave source for calibration. good idea!
  • Inductively powered @ 1Mhz.
  • FM modulation at 39.2Mz and 43.9Mhz. COTS?
    • The implantable electronics are bulky as can be seen in Figs. 14 and ​and 19. (what a mess?!)
  • 3 patients, 4 years in 2 patients that dies from unrelated causes, over 3 years in a third.
  • describe construction of electrode -- not complicated.

____References____

[0] Bartels J, Andreasen D, Ehirim P, Mao H, Seibert S, Wright EJ, Kennedy P, Neurotrophic electrode: method of assembly and implantation into human motor speech cortex.J Neurosci Methods 174:2, 168-76 (2008 Sep 30)
[1] Kennedy PR, The cone electrode: a long-term electrode that records from neurites grown onto its recording surface.J Neurosci Methods 29:3, 181-93 (1989 Sep)

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ref: -0 tags: kennedy neurotropic electrode date: 01-19-2017 01:47 gmt revision:2 [1] [0] [head]

PMID-9237542 Activity of single action potentials in monkey motor cortex during long-term task learning. Kennedy PR1, Bakay RA.'''

  • 2mm glass cone electrode, filled with matrigel and nerve growth factor, was implanted into layer 5/6 of the monkey motor cortex.
    • Matrigel: a solubilized basement membrane preparation extracted from the Engelbreth-Holm-Swarm (EHS) mouse sarcoma, a tumor rich in such ECM proteins as laminin (a major component), collagen IV, heparin sulfate proteoglycans, entactin/nidogen, and a number of growth factors.
      • Used extensively in cell culture work.
      • Previous studies used 'autologous sciatic nerve'.
    • Of note, this was no less invasive than a Utah array; it's virtue lies in stability.
  • Incgrowing cells became mylenated [4]
  • Recording quality about the same as extracellular recordings: 40 to 80um amplitude.
    • Makes sense, as there was no reason for the neurites (no somas grew in!) to attach to the gold microwires.
  • Rather short communication describing what appears to be the idiosyncratic behavior of 3 neurons...

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ref: -0 tags: serial electron microscopy Lichtman reconstruction nervous tissue date: 01-17-2017 23:32 gmt revision:0 [head]

PMID-26232230 Saturated Reconstruction of a Volume of Neocortex.

  • Data presented at Cell "Big Questions in Neuroscience", perhaps the most impressive of the talks.

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ref: -0 tags: neural coding rats binary permutation retrosplenial basolateral amygdala tetrode date: 12-19-2016 07:39 gmt revision:1 [0] [head]

PMID-27895562 Brain Computation Is Organized via Power-of-Two-Based Permutation Logic.

  • Nice and interesting data, sort of kitchen sink of experiments but ...
  • At first blush it seems they have re-discovered Haar wavelets / the utility of binary decompositions.
  • Figures 9 and 10, however, suggest a discriminable difference in representation in layers 2/3 and 5/6, supporting their binary hypothesis.
    • The former targeted the mouse's large retrosplenial cortex; the latter, the hamster's prelimbic cortex.

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ref: -0 tags: L1 cell adhesion neural implants microglia DRG spinal cord dorsal root inflammation date: 11-19-2016 22:55 gmt revision:1 [0] [head]

PMID-22750248 In vivo effects of L1 coating on inflammation and neuronal health at the electrode-tissue interface in rat spinal cord and dorsal root ganglion.

  • Kolarcik CL1, Bourbeau D, Azemi E, Rost E, Zhang L, Lagenaur CF, Weber DJ, Cui XT.
  • Quote: With L1, neurofilament staining was significantly increased while neuronal cell death decreased.
  • These results indicate that L1-modified electrodes may result in an improved chronic neural interface and will be evaluated in recording and stimulation studies.
  • Ok, so this CAM seems to mitigate against microglia / inflammation, but how was it selected vs any of the other CAMs and surface proteins? (This domain is almost completely unknown by me..)
  • Ultimate strategy likely to be a broad combination of mechanical (size, flexibility), biochemical (inflammation, cell migration), electrochamical (surface coatings) and vasculature-avoiding approaches.

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ref: -0 tags: LCP polymer Zeus tensile modulus date: 11-11-2016 20:39 gmt revision:0 [head]

https://www.zeusinc.com/materials/lcp-liquid-crystal-polymer

  • UTS 1.0 GPa; 80 MPa Youngs modulus.
  • No data on moisture uptake or molecular structure.

{1358}
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ref: -0 tags: china trustwothiness social engineering communism date: 10-31-2016 05:42 gmt revision:1 [0] [head]

China 'social credit': Beijing sets up huge system

So long as it purports to measure just one social variable -- 'trustworthiness' -- it might be a good idea. Many commerce websites (.. ebay ..) have these sort of rating systems already, and they are useful. When humans live in smaller communities something like this is in the shared consciousness.

Peering into everyone's purchasing habits and hobbies, however, seems like it will be grossly myopic and, as the article says, Orwellian. Likely they will train a deep-belief network on past data of weakly and communist party defined success, with all purchasing and social media as the input data, and use that in the proprietary algorithm for giving people their scalars to optimize. This would be the ultimate party control tool -- a great new handle for controlling people's minds, even 'better' than capitalism.

Surprising that the article only hints at this, and that the Chinese themselves seem rather clueless that it's a power play. In this sense, it's a very clever play to link it to reproduction.


Other comments:

These sorts of systems may be necessary in highly populated countries, where freedom and individuality are less valued and social cohesion is requisite.

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ref: -0 tags: tungsten rhenium refactory metals book russia metalurgy date: 10-31-2016 05:14 gmt revision:1 [0] [head]

Physical Metallurgy of Refactory Metals and Alloys

Properties of tungsten-rhenium alloys

  • Luna metals suggests 3% Re improves the tensile strength of the alloy; Concept Alloys has 26% Re.
  • This paper mesured 20% Re, with a strength of 1.9 GPa; actual drawn tungsten wire has a strength of 3.3 GPa.
    • Drawing and cold working greatly affects metal, as always!

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ref: -0 tags: PEDOT electropolymerization electroplating gold TFB borate counterion acetonitrile date: 10-18-2016 07:49 gmt revision:3 [2] [1] [0] [head]

Electrochemical and Optical Properties of the Poly(3,4-ethylenedioxythiophene) Film Electropolymerized in an Aqueous Sodium Dodecyl Sulfate and Lithium Tetrafluoroborate Medium

  • EDOT has a higher oxidation potential than water, which makes polymers electropolymerized from water "poorly defined".
  • Addition of SDS lowers the oxidation potential to 0.76V, below that of EDOT in acetonitrile at 1.1V.
  • " The potential was first switched from open circuit potential to 0.5 V for 100 s before polarizing the electrode to the desired potential. This initial step was to allow double-layer charging of the Au electrode|solution interface, which minimizes the distortion of the polymerization current transient by double-layer capacitance charging.17,18 "
    • Huh, interesting.
  • Plated at 0.82 - 0.84V, 0.03M EDOT conc.
  • 0.1M LiBF4 anion / electrolyte; 0.07M SDS sufactant.
    • This SDS is incorporated into the film, and affects redox reactions as shown in the cyclic voltammagram (fig 4)
      • Doping level 0.36
    • BF4-, in comparison, can be driven out of the film.

Improvement of the Electrosynthesis and Physicochemical Properties of Poly(3,4-ethylenedioxythiophene) Using a Sodium Dodecyl Sulfate Micellar Aqueous Medium

  • "The oxidation potential of thiopene = 1.8V; water = 1.23V.
  • Claim: "The polymer films prepared in micellar medium [SDS] are more stable than those obtained in organic solution as demonstrated by the fact that, when submitted to a great number of redox cycles (n ≈ 50), there is no significant loss of their electroactivity (<10%). These electrochemical properties are accompanied by color changes of the film which turns from blue-black to red-purple upon reduction."
  • Estimate that there is about 21% DS- anions in the PEDOT - SDS films.
    • Cl - was at ~ 7%.
  • I'm still not sure about incorporating soap into the electroplating solution.. !

Electrochemical Synthesis of Poly(3,4-ethylenedioxythiophene) on Steel Electrodes: Properties and Characterization

  • 0.01M EDOT and 0.1M LiClO4 in acetonitrile.
  • Claim excellent adhesion & film properties to 316 SS.
  • Oxidation / electrodeposition at 1.20V; voltages higher than 1.7V resulted in flaky films.

PMID-20715789 Investigation of near ohmic behavior for poly(3,4-ethylenedioxythiophene): a model consistent with systematic variations in polymerization conditions.

  • Again use acetonitrile.
  • 1.3V vs Ag/AgCl electrode.
  • Perchlorate and tetraflouroborate both seemed the best counterions (figure 4).
  • Figure 5: Film was difficult to remove from surface.
    • They did use a polycrystaline Au layer:
    • "The plating process was allowed to run for 1 min (until approximately 100 mC had passed) at a constant potential of 0.3 V versus Ag/AgCl in 50 mM HAuCl4 prepared in 0.1 M NaCl."
  • Claim that the counterions are trapped; not in agreement with the SDS study above.
  • "Conditions for the consistent production of conducting polymer films employing potentiostatic deposition at 1.3 V for 60-90 s have been determined. The optimal concentration of the monomer is 0.0125 M, and that of the counterion is 0.05 M. "

PMID-24576579 '''Improving the performance of poly(3,4-ethylenedioxythiophene) for brain–machine interface applications"

  • Show that TFB (BF4-) is a suitable counterion for EDOT electropolymerization.
  • Comparison is between PEDOT:TFB deposited in an anhydrous acetronitrile solution, and PEDOT:PSS deposited in an aqueous solution.
    • Presumably the PSS brings the EDOT into solution (??).
  • figure 3 is compelling, but long-term, electrodes are not that much better than Au!
    • Maybe we should just palate with that.

PEDOT-modified integrated microelectrodes for the detection of ascorbic acid, dopamine and uric acid

  • Direct comparison of acetonitrile and water solvents for electropolymerization of EDOT.
  • "PEDOT adhesion is best on gold surface due to the strong interactions between gold and sulphur atoms.
  • images/1353_2.pdf
    • Au plating is essential!

{1354}
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ref: -0 tags: David Kleinfeld penetrating arterioles perfusion cortex vasculature date: 10-17-2016 23:24 gmt revision:1 [0] [head]

PMID-17190804 Penetrating arterioles are a bottleneck in the perfusion of neocortex.

  • Focal photothrombosis was used to occlude single penetrating arterioles in rat parietal cortex, and the resultant changes in flow of red blood cells were measured with two-photon laser-scanning microscopy in individual subsurface microvessels that surround the occlusion.
  • We observed that the average flow of red blood cells nearly stalls adjacent to the occlusion and remains within 30% of its baseline value in vessels as far as 10 branch points downstream from the occlusion.
  • Preservation of average flow emerges 350 mum away; this length scale is consistent with the spatial distribution of penetrating arterioles
  • Rose bengal photosensitizer.
  • 2p laser scanning microscopy.
  • Downstream and connected arterioles show a dramatic reduction in blood flow, even 1-4 branches in; there is little reduncancy (figure 2)
  • Measured a good number of vessels (and look at their density!); results are satisfactorily quantitative.
  • Vessel leakiness extends up to 1.1mm away (!) (figure 5).

{1270}
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ref: -0 tags: gold micrograin recording electrodes electroplating impedance date: 10-17-2016 20:28 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-23071004 Gold nanograin microelectrodes for neuroelectronic interfaces.

  • We report a single-cell sized microelectrode, which has unique gold nanograin structures, using a simple electrochemical deposition method.
  • Fabricated microelectrode had a sunflower shape with 1-5 (um of micropetals along the circumference of the microelectrode and 500 nm nanograins at the center.
  • The nanograin electrodes had 69-fold decrease of impedance and 10-fold increase in electrical stimulation capability compared to unmodified flat gold microelectrodes.
  • images/1270_1.pdf pdf
  • The deposition was conducted with an aqueous solution containing 25 mM HAuCl (HAuCl · 3H O, Sigma-Aldrich, MO, 4 4 2USA) and 20 g/L polyvinylpyrrolidone (surfactant, stabilizing agent)

{1352}
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ref: -0 tags: Charles Lieber syringe-injectable electronics SU-8 chronic flexible date: 10-14-2016 23:30 gmt revision:1 [0] [head]

PMID-27571550 Stable long-term chronic brain mapping at the single-neuron level.

  • Fu TM, Hong G1, Zhou T1, Schuhmann TG, Viveros RD2, Lieber CM.
  • 8 months with only 800nm of Su-8 (400nm of insulation!!). This is both surprising and very impressive; we have to step up our game!
  • In a mouse, too - their surgical technique must be very good. Mice only live ~ 2 years anyway.
  • Figure 3 -- stability -- incredible.
  • Recording sites were bare platinum, 20um diameter; stimulation sites were also bare Pt, 150um dia.
    • No plating or mircowire-fets, so far as I can see; electrode impedances were stable at 200 - 600k (supplementary figure 12).

{1327}
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ref: -0 tags: ice charles lieber silicon nanowire probes su-8 microwire extracellular date: 10-14-2016 23:28 gmt revision:2 [1] [0] [head]

PMID-26436341 Three-dimensional macroporous nanoelectronic networks as minimally invasive brain probes.

  • Xie C1, Liu J1, Fu TM1, Dai X1, Zhou W1, Lieber CM1,2.
  • Again, use silicon nanowire transistors as sensing elements. These seem rather good; can increase the signal, and do not suffer from shunt resistance / capacitance like wires.
    • They're getting a lot of mileage out of the technology; initial pub back in 2006.
  • Su-8, Cr/Pd/Cr (stress elements) and Cr/Au/Cr (conductor) spontaneously rolled into a ball, then the froze in LN2. Devices seemed robust to freezing in LN2.
  • 300-500nm Su-8 passivation layers, as with the syringe injectable electrodes.
  • 3um trace / 7um insulation (better than us!)
  • Used 100nm Ni release layer; thin / stiff enough Su-8 with rigid Si support chip permitted wirebonding a connector (!!)
    • Might want to use this as well for our electrodes -- of course, then we'd have to use the dicing saw, and free-etch away a Ni (or Al?) polyimide adhesion layer -- or use Su-8 like them. See figure S-4
  • See also {1352}

{1351}
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ref: -0 tags: Ciske Kalaska date: 10-11-2016 17:11 gmt revision:0 [head]

PMID-20345247 Neural mechanisms for interacting with a world full of choices

  • Cisek P1, Kalaska JF.
  • "Affordance competition hypothesis" -- idea is that there is no specialization of areas per se, but rather a distribution of behavior-related areas, ones which specialize in task and stimulus/motor relevance, rather than processing and representation.
    • Similar, but distinct, from Minsky's Society of Mind.
    • Broadly supported by experimental evidence, which shows little 'conventional' representation, but plenty of sensory and motor representation, nearly everywhere..
  • Based on Jean Piaget (1954), "who suggested that the abstract cognitive abilities of adult humans are constructed upon the basis of the sensorimotor interactions experienced as a child."
    • "This is supported by a variety of neural studies, which include the classic experiments of Held & Hein (1963), who found that the visual behavior of newborn kittens did not develop properly unless they were allowed to exert their own active control upon their visual input."
  • Good ideas, good reformulation, but needs to be fleshed out a bit more; need to review the citing literature.

{1350}
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ref: -0 tags: ultrasonic BMI monkey LFP intan nordic Ozturk UCSD date: 09-30-2016 19:38 gmt revision:2 [1] [0] [head]

A Wireless 32-Channel Implantable Bidirectional Brain Machine Interface

  • Yi Su 1,2,*, Sudhamayee Routhu 2, Kee S. Moon 3, Sung Q. Lee 4, WooSub Youm 4 and Yusuf Ozturk 2,
  • Only LFP from a utah array, but solid work none-the-less.
  • 20V unipolar stimulation.
    • Through separate recording and stimulation electrodes.
  • 35mm x 10mm.
  • LFP due to limited bandwidth.
    • Less RF bw & compression that the wireless system I designed 6 years ago.
    • Reason: "Further, in order to analyze the integrative synaptic processes, LFP is the signal of interest instead of spikes, because synaptic processes cannot be captured by spike activity of a small number of neurons"
captured by spike activity of a small number of neurons.
  • Reference use of DuraGen followed by silicone elastomer.
  • Didn't cite us.

{1349}
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ref: -0 tags: bone regrowth hyperelastic 3d print implant hydroxyapatite polycaptolactone date: 09-30-2016 18:27 gmt revision:0 [head]

Hyperelastic “bone”: A highly versatile, growth factor–free, osteoregenerative, scalable, and surgically friendly biomaterial

  • (From the abstract): hyperelastic “bone” is composed of 90 weight % (wt %) hydroxyapatite and 10 wt % polycaprolactone or poly(lactic-co-glycolic acid),
  • Can be rapidly three-dimensionally (3D) printed (up to 275 cm3/hour) from room temperature extruded liquid inks.
  • Mechanical properties: ~32 to 67% strain to failure, ~4 to 11 MPa elastic modulus & was highly absorbent (50% material porosity)
  • Supported cell viability and proliferation, and induced osteogenic differentiation of bone marrow–derived human mesenchymal stem cells cultured in vitro over 4 weeks without any osteo-inducing factors in the medium.
  • HB did not elicit a negative immune response, became vascularized, quickly integrated with surrounding tissues, and rapidly ossified and supported new bone growth without the need for added biological factors.

{1348}
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ref: -0 tags: David Kleinfeld cortical vasculature laser surgery network occlusion flow date: 09-23-2016 06:35 gmt revision:1 [0] [head]

Heller Lecture - Prof. David Kleinfeld

  • Also mentions the use of LIBS + q-switched laser for precisely drilling holes in the scull. Seems to work!
    • Use 20ns delay .. seems like there is still spectral broadening.
    • "Turn neuroscience into an industrial process, not an art form" After doing many surgeries, agreed!
  • Vasodiliation & vasoconstriction is very highly regulated; there is not enough blood to go around.
    • Vessels distant from a energetic / stimulated site will (net) constrict.
  • Vascular network is most entirely closed-loop, and not tree-like at all -- you can occlude one artery, or one capillary, and the network will route around the occlusion.
    • The density of the angio-architecture in the brain is unique in this.
  • Tested micro-occlusions by injecting rose bengal, which releases free radicals on light exposure (532nm, 0.5mw), causing coagulation.
  • "Blood flow on the surface arteriole network is insensitive to single occlusions"
  • Penetrating arterioles and venules are largely stubs -- single unbranching vessels, which again renders some immunity to blockage.
  • However! Occlusion of a penetrating arteriole retards flow within a 400 - 600um cylinder (larger than a cortical column!)
  • Occulsion of many penetrating vessels, unsurprisingly, leads to large swaths of dead cortex, "UBOS" in MRI parlance (unidentified bright objects).
  • Death and depolarizing depression can be effectively prevented by excitotoxicity inhibitors -- MK801 in the slides (NMDA blocker, systemically)

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ref: -0 tags: laser induced breakdown spectroscopy for surgery tissue differentiation date: 09-22-2016 19:26 gmt revision:0 [head]

PMID-25426327 Laser induced breakdown spectroscopy for bone and cartilage differentiation - ex vivo study as a prospect for a laser surgery feedback mechanism.

  • Mehari F1, Rohde M2, Knipfer C2, Kanawade R1, Klämpfl F1, Adler W3, Stelzle F4, Schmidt M1.
  • Tested on pig ear cartilage & cortical bone.
  • 532nm, Q-switched, flashlamp-pumped Nd:YAG, 80mJ pulse energy, 10ns, 1Hz.
  • Commercial spectrogram; light collected with 50um fiber optic connector.
    • We could probably put this in line with the laser mirrors, probably..
  • Super clean results: see any of the figures.
    • AUC = 1.00 !!

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ref: -0 tags: super resolution imaging PALM STORM fluorescence date: 09-21-2016 05:57 gmt revision:0 [head]

PMID-23900251 Parallel super-resolution imaging

  • Christopher J Rowlands, Elijah Y S Yew, and Peter T C So
  • Though this is a brief Nature intro article, I found it to be more usefully clear than the wikipedia articles on super-resolution techniques.
  • STORM and PALM seek to stochastically switch fluorophores between emission and dark states, and are parallel but stochastic; STED and RESOLFT use high-intensity donut beams to stimulate emission (STED) or photobleach (RESOLFT) fluorophores outside of an arbitrarily-small location.
    • All need gaussian-fitting to estimate emitter location from the point-spread function.
  • This article comments on a clever way of making 1e5 donuts for parallel (as opposed to rastered) STED / RESOLFT.
  • I doubt stetting up a STED microscope is at all easy; to get these resolutions, everything must be still to a few nm!

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ref: -0 tags: nucleus accumbens caudate stimulation learning enhancement MIT date: 09-20-2016 23:51 gmt revision:1 [0] [head]

Temporally Coordinated Deep Brain Stimulation in the Dorsal and Ventral Striatum Synergistically Enhances Associative Learning

  • Monkeys had to learn to associate an image with one of 4 reward targets.
    • Fixation period, movement period, reward period -- more or less standard task.
    • Blocked trial structure with randomized associations + control novel images + control familiar images.
  • Timed stimulation:
    • Nucleus Accumbens during fixation period
      • Shell not core; non-hedonic in separate test.
    • Caudate (which part -- targeting?) during feedback on correct trials.
  • Performance on stimulated images improved in reaction time, learning rate, and ultimate % correct.
  • Small non-significant improvement in non-stimulated novel image.
  • Wonder how many stim protocols they had to try to get this correct?

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ref: -0 tags: planned economy red plenty date: 08-08-2016 05:54 gmt revision:0 [head]

http://crookedtimber.org/2012/05/30/in-soviet-union-optimization-problem-solves-you/#demographic-back

  • Quote: "That planning is not a viable alternative to capitalism (as opposed to a tool within it) should disturb even capitalism’s most ardent partisans. It means that their system faces no competition, nor even any plausible threat of competition."
    • And therefore not only cannot be improved, but must degrade with time. But see below.
  • Quote: What we can do is try to find the specific ways in which these powers we have conjured up are hurting us, and use them to check each other, or deflect them into better paths. Sometimes this will mean more use of market mechanisms, sometimes it will mean removing some goods and services from market allocation, either through public provision or through other institutional arrangements. Sometimes it will mean expanding the scope of democratic decision-making (for instance, into the insides of firms), and sometimes it will mean narrowing its scope (for instance, not allowing the demos to censor speech it finds objectionable). Sometimes it will mean leaving some tasks to experts, deferring to the internal norms of their professions, and sometimes it will mean recognizing claims of expertise to be mere assertions of authority, to be resisted or countered.
    • I like to think of this as a very unstable equilibrium: the only way to maintain function is to continuously expend energy to shore up and change the market, politics, and society in general; the specific regulatory solution has complexity commensurate with the complexity of the economy regulated, and it must adapt on the same scales that the market economy changes.
    • Perhaps to do this, it needs a self-reflective faculty, to know which parts of itself need changing; otherwise, you'd need to have a regulator regulating the regulator, and who is to prevent that from agglomerating power. Yet this too is an unstable equilibrium.

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ref: -0 tags: NC state tap drill chart date: 08-02-2016 18:38 gmt revision:0 [head]

http://amasci.com/tesla/Tap_Drill_Chart.html

by way of: https://m.reddit.com/r/engineering/comments/4ry07t/does_anyone_have_a_stored_copy_of_this_tap_and/

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ref: -0 tags: image registration optimization camera calibration sewing machine date: 07-15-2016 05:04 gmt revision:20 [19] [18] [17] [16] [15] [14] [head]

Recently I was tasked with converting from image coordinates to real world coordinates from stereoscopic cameras mounted to the end-effector of a robot. The end goal was to let the user (me!) click on points in the image, and have the robot record that position & ultimately move to it.

The overall strategy is to get a set of points in both image and RW coordinates, then fit some sort of model to the measured data. I began by printing out a grid of (hopefully evenly-spaced and perpendicular) lines via a laserprinter; spacing was ~1.1 mm. This grid was manually aligned to the axes of robot motion by moving the robot along one axis & checking that the lines did not jog.

The images were modeled as a grating with quadratic phase in u,v texture coordinates:

p h(u,v)=sin((a hu/1000+b hv/1000+c h)v+d hu+e hv+f h)+0.97 (1)

p v(u,v)=sin((a vu/1000+b vv/1000+c v)u+d vu+e vv+f v)+0.97 (2)

I(u,v)=16p hp v/(2+16p h 2+16p v 2) (3)

The 1000 was used to make the parameter search distribution more spherical; c h,c v were bias terms to seed the solver; 0.97 was a duty-cycle term fit by inspection to the image data; (3) is a modified sigmoid.

I was then optimized over the parameters using a GPU-accelerated (CUDA) nonlinear stochastic optimization:

(a h,b h,d h,e h,f ha v,b v,d v,e v,f v)=Argmin u v(I(u,v)Img(u,v)) 2 (4)

Optimization was carried out by drawing parameters from a normal distribution with a diagonal covariance matrix, set by inspection, and mean iteratively set to the best solution; horizontal and vertical optimization steps were separable and carried out independently. The equation (4) was sampled 18k times, and equation (3) 34 billion times per frame. Hence the need for GPU acceleration.

This yielded a set of 10 parameters (again, c h and c v were bias terms and kept constant) which modeled the data (e.g. grid lines) for each of the two cameras. This process was repeated every 0.1 mm from 0 - 20 mm height (z) from the target grid, resulting in a sampled function for each of the parameters, e.g. a h(z) . This required 13 trillion evaluations of equation (3).

Now, the task was to use this model to generate the forward and reverse transform from image to world coordinates; I approached this by generating a data set of the grid intersections in both image and world coordinates. To start this process, the known image origin u origin z=0,v origin z=0 was used to find the corresponding roots of the periodic axillary functions p h,p v :

3π2+2πn h=a huv/1000+b hv 2/1000+(c h+e h)v+d hu+f h (5)

3π2+2πn h=a vu 2/1000+b vuv/1000+(c v+d v)u+e vv+f v (6)

Or ..

n h=round((a huv/1000+b hv 2/1000+(c h+e h)v+d hu+f h3π2)/(2π) (7)

n v=round((a vu 2/1000+b vuv/1000+(c v+d v)u+e vv+f v3π2)/(2π) (8)

From this, we get variables n h,origin z=0andn v,origin z=0 which are the offsets to align the sine functions p h,p v with the physical origin. Now, the reverse (world to image) transform was needed, for which a two-stage newton scheme was used to solve equations (7) and (8) for u,v . Note that this is an equation of phase, not image intensity -- otherwise this direct method would not work!

First, the equations were linearized with three steps of (9-11) to get in the right ballpark:

u 0=640,v 0=360

n h=n h,origin z+[30..30],n v=n v,origin z+[20..20] (9)

B i=[3π2+2πn ha hu iv i/1000b hv i 2f h 3π2+2πn va vu i 2/1000b vu iv if v] (10)

A i=[d h c h+e h c v+d v e v] and

[u i+1 v i+1]=mldivide(A i,B i) (11) where mldivide is the Matlab operator.

Then three steps with the full Jacobian were made to attain accuracy:

J i=[a hv i/1000+d h a hu i/1000+2b hv i/1000+c h+e h 2a vu i/1000+b vv i/1000+c v+d v b vu i/1000+e v] (12)

K i=[a hu iv i/1000+b hv i 2/1000+(c h+e h)v i+d hu i+f h3π22πn h a vu i 2/1000+b vu iv i/1000+(c v+d v)u i+e vv+f v3π22πn v] (13)

[u i+1 v i+1]=[u i v i]J i 1K i (14)

Solutions (u,v) were verified by plugging back into equations (7) and (8) & verifying n h,n v were the same. Inconsistent solutions were discarded; solutions outside the image space [0,1280),[0,720) were also discarded. The process (10) - (14) was repeated to tile the image space with gird intersections, as indicated in (9), and this was repeated for all z in (0..0.1..20) , resulting in a large (74k points) dataset of (u,v,n h,n v,z) , which was converted to full real-world coordinates based on the measured spacing of the grid lines, (u,v,x,y,z) . Between individual z steps, n h,originn v,origin was re-estimated to minimize (for a current z ):

(u origin z+0.1u origin z+0.1) 2+(v origin z+0.1+v origin z) 2 (15)

with grid-search, and the method of equations (9-14). This was required as the stochastic method used to find original image model parameters was agnostic to phase, and so phase (via parameter f ) could jump between individual z measurements (the origin did not move much between successive measurements, hence (15) fixed the jumps.)

To this dataset, a model was fit:

[u v]=A[1 x y z x 2 y 2 z 2 w 2 xy xz yz xw yw zw] (16)

Where x=x10 , y=y10 , z=z10 , and w=2020z . w was introduced as an axillary variable to assist in perspective mapping, ala computer graphics. Likewise, x,y,z were scaled so the quadratic nonlinearity better matched the data.

The model (16) was fit using regular linear regression over all rows of the validated dataset. This resulted in a second set of coefficients A for a model of world coordinates to image coordinates; again, the model was inverted using Newton's method (Jacobian omitted here!). These coefficients, one set per camera, were then integrated into the C++ program for displaying video, and the inverse mapping (using closed-form matrix inversion) was used to convert mouse clicks to real-world coordinates for robot motor control. Even with the relatively poor wide-FOV cameras employed, the method is accurate to ±50μm , and precise to ±120μm .

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ref: Gradinaru-2009.04 tags: Deisseroth DBS STN optical stimulation 6-OHDA optogenetics date: 05-10-2016 23:48 gmt revision:8 [7] [6] [5] [4] [3] [2] [head]

PMID-19299587[0] Optical Deconstruction of Parkinsonian Neural Circuitry.

  • Viviana Gradinaru, Murtaza Mogri, Kimberly R. Thompson, Jaimie M. Henderson, Karl Deisseroth
  • DA depletion of the SN leads to abnormal activity in the BG ; HFS (>90Hz) of the STN has been found to be therapeutic, but the mechanism is imperfectly understood.
    • lesions of the BG can also be therapeutic.
  • Used chanelrhodopsin (light activated cation channel (+)) which are expressed by cell type specific promoters. (transgenic animals). Also used halorhodopsins, which are light activated chloride pumps (inhibition).
    • optogenetics allows simultaneous optical stimulation and electrical recording without artifact.
  • Made PD rats by 6-hydroxydopamine unilaterally into the medial forebrain bundle of rats.
  • Then they injected eNpHr (inhibitory) opsin vector targeting excitatory neurons (under control of the CaMKIIa receptor) to the STN as identified stereotaxically & by firing pattern.
    • Electrical stimulation of this area alleviated rotational behavior (they were hemiparkinsonian rats), but not optical inhibition of STN.
  • Alternately, the glia in STN may be secreting molecules that modulate local circuit activity; it has been shown that glial-derived factor adenosine accumulates during DBS & seems to help with attenuation of tremor.
    • Tested this by activating glia with ChR2, which can pass small Ca+2 currents.
    • This worked: blue light halted firing in the STN; but, again, no behavioral trace of the silencing was found.
  • PD is characterized by pathological levels of beta oscillations in the BG, and synchronizing STN with the BG at gamma frequencies may ameliorate PD symptoms; while sync. at beta will worsen -- see [1][2]
  • Therefore, they tried excitatory optical stimulation of excitatory STN neurons at the high frequencies used in DBS (90-130Hz).
    • HFS to STN failed, again, to produce any therapeutic effect!
  • Next expressed channel rhodopsin in only projection neurons Thy1::ChR2 (not excitatory cells in STN), again did optotrode (optical stim, eletrical record) recordings.
    • HFS of afferent fibers to STN shut down most of the local circuitry there, with some residual low-amplitude high frequency burstiness.
    • Observed marked effects with this treatment! Afferent HFS alleviated Parkinsonian symptoms, profoundly, with immediate reversal once the laser was turned off.
    • LFS worsened PD symptoms, in accord with electrical stimulation.
    • The Thy1::ChR2 only affected excitatory projections; GABAergic projections from GPe were absent. Dopamine projections from SNr were not affected by the virus either. However, M1 layer V projection neurons were strongly labeled by the retrovirus.
      • M1 layer V neurons could be antidromically recruited by optical stimulation in the STN.
  • Selective M1 layer V HFS also alleviated PD symptoms ; LFS had no effect; M2 (Pmd/Pmv?) LFS causes motor behavior.
  • Remind us that DBS can treat tremor, rigidity, and bradykinesia, but is ineffective at treating speech impairment, depression, and dementia.
  • Suggest that axon tract modulation could be a common theme in DBS (all the different types..), as activity in white matter represents the activity of larger regions compactly.
  • The result that the excitatory fibers of projections, mainly from the motor cortex, matter most in producing therapeutic effects of DBS is counterintuitive but important.
    • What do these neurons do normally, anyway? give a 'copy' of an action plan to the STN? What is their role in M1 / the BG? They should test with normal mice.

____References____

[0] Gradinaru V, Mogri M, Thompson KR, Henderson JM, Deisseroth K, Optical Deconstruction of Parkinsonian Neural Circuitry.Science no Volume no Issue no Pages (2009 Mar 19)
[1] Eusebio A, Brown P, Synchronisation in the beta frequency-band - The bad boy of parkinsonism or an innocent bystander?Exp Neurol no Volume no Issue no Pages (2009 Feb 20)
[2] Wingeier B, Tcheng T, Koop MM, Hill BC, Heit G, Bronte-Stewart HM, Intra-operative STN DBS attenuates the prominent beta rhythm in the STN in Parkinson's disease.Exp Neurol 197:1, 244-51 (2006 Jan)

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ref: -2016 tags: 6-OHDA parkinsons model warren grill simulation date: 05-10-2016 23:30 gmt revision:4 [3] [2] [1] [0] [head]

PMID-26867734 A biophysical model of the cortex-basal ganglia-thalamus network in the 6-OHDA lesioned rat model of Parkinson’s disease

  • Kumaravelu K1, Brocker DT1, Grill WM
  • Background: Although animal models (6-OHDA rats, MPTP mk) are rendered parkinsonian by a common mechanism (loss of dopaminergic neurons), there is considerable variation in the neuronal activity underlying the pathophysiology, including differences in firing rates, firing patterns, responses to cortical stimulation, and neuronal synchronization across different basal ganglia (BG) structures (Kita and Kita 2011;Nambu et al. 2000).
    • Yep. Highly idiopathic disease.
    • Claim there are good models of the MPTP monkey:
      • PMID-20309620 Modeling shifts in the rate and pattern of subthalamopallidal network activity during deep brain stimulation.
      • PMID-22805068 Network effects of subthalamic deep brain stimulation drive a unique mixture of responses in basal ganglia output.
  • Biophysical model of the cortex - basal ganglia - thalamus circuit
    • Hodgkin-Huxley type.
      • Single compartment neurons.
    • Validated by comparing responses of the BG to CTX stimulation.
    • Details, should they be important:
      • Each rCortex (regularly spiking) neuron
        • excitatory input from one TH neuron
        • inhibitory input from four randomly selected iCortex neurons.
        • Izhikevich model.
      • Each iCortex (fast inhibitory) neuron
        • excitatory input from four randomly selected rCortex neurons.
      • Each dStr (direct, D1/D5, ex) neuron
        • excitatory input from one rCortex neuron
        • inhibitory axonal collaterals from three randomly selected dStr neurons.
      • Each idStr (indirect, D2, inhib) neuron
        • excitatory input from one rCortex neuron
        • inhibitory axonal collaterals from four randomly selected idStr neurons.
      • Each STN neuron
        • inhibitory input from two GPe neurons
        • excitatory input from two rCortex neurons.
        • DBS modeled as a somatic current.
      • Each GPe neuron
        • inhibitory axonal collaterals from any two other GPe neurons
        • inhibitory input from all idStr neurons.
      • Each GPi neuron
        • inhibitory input from two GPe neurons
        • inhibitory input from all dStr neurons.
      • Some GPe/GPi neurons receive
        • excitatory input from two STN neurons,
        • while others do not.
      • Each TH neuron receives inhibitory input from one GPi neuron.
  • Diseased state:
    • Loss of striatal dopamine is accompanied by an increase in acetylcholine levels (Ach) in the Str (Ikarashi et al. 1997)
      • This results in a reduction of M-type potassium current in both the direct and indirect MSNs. (2.6 -> 1.5)
    • Dopamine loss results in reduced sensitivity of direct Str MSN to cortical stimulation (Mallet et al. 2006)
      • corticostriatal synaptic conductance from 0.07 to 0.026
    • Striatal dopamine depletion causes an increase in the synaptic strength of intra-GPe axonal collaterals resulting in aberrant GPe firing (Miguelez et al. 2012)
      • Increase from 0.125 to 0.5.
  • Good match to experimental rats:
  • Ok, so this is a complicated model (they aim to be the most complete to-date). How sensitive is it to parameter perturbations?
    • Noticeable ~20 Hz oscillations in BG in PD condition
    • ~9 Hz in STN & GPi.
  • And how well do the firing rates match experiment?
    • Not very. Look at the error bars.
  • What does DBS (direct current injection into STN neurons) do?
    • Se d,e,f: stochastic parameter; g,h,i: (semi) stochastic wiring.
  • Another check: NMDA antagonist into STN suppressed STN beta band oscillations in 6-OHDA lesioned rats (Pan et al. 2014).
    • Analysis of model GPi neurons revealed that episodes of beta band oscillatory activity interrupted alpha oscillatory activity in the PD state (Fig. 9a, b), consistent with experimental evidence that episodes of tremor-related oscillations desynchronized beta activity in PD patients (Levy et al. 2002).
  • What does DBS, at variable frequencies, do oscillations in the circuit?
  • How might this underly a mechanism of action?

Overall, not a bad paper. Not very well organized, which is not assisted by the large amount of information presented, but having slogged through the figures, I'm somewhat convinced that the model is good. This despite my general reservations of these models: the true validation would be to have it generate actual behavior (and learning)!

Lacking this, the approximations employed seem like a step forward in understanding how PD and DBS work. The results and discussion are consistent with {1255}, but not {711}, which found that STN projections from M1 (not the modulation of M1 projections to GPi, via efferents from STN) truly matter.

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ref: -2012 tags: Emo Todorov contact invariant animation optimization complex motor behavior date: 05-04-2016 17:34 gmt revision:3 [2] [1] [0] [head]

* Watch the [http://homes.cs.washington.edu/~todorov/index.php?video=MordatchSIGGRAPH12&paper=Mordatch,%20SIGGRAPH%202012 movies! Discovery of complex behaviors through contact-invariant optimization]

  • Complex movements tend to have phases within which the set of active contacts (hands, feet) remains invariant (hence can exert forces on the objects they are contacting, or vice versa).
  • Discovering suitable contact sets is the central goal of optimization in our approach.
    • Once this is done, optimizing the remaining aspects of the movement tends to be relatively straightforward.
    • They do this through axillary scalar variables which indicate whether the a contact is active or not, hence whether to enable contact forces.
      • Allows the optimizer to 'realize' that movements should have phases.
      • Also "shapes the energy landscape to be smoother and better behaved"
  • Initial attempts to make these contact axillary variables discrete -- when and where -- which was easy for humans to specify, but made optimization intractable.
    • Motion between contacts was modeled as a continuous feedback system.
  • Instead, the contact variables c i have to be continuous.
  • Contact forces are active only when c i is 'large'.
    • Hence all potential contacts have to be enumerated in advance.
  • Then, parameterize the end effector (position) and use inverse kinematics to figure out joint angles.
  • Optimization:
    • Break the movement up into a predefined number of phases, equal duration.
    • Interpolate end-effector with splines
    • Physics constraints are 'soft' -- helps the optimizer : 'powerful continuation methods'
      • That is, weight different terms differently in phases of the optimization process.
      • Likewise, appendages are allowed to stretch and intersect, with a smooth cost.
    • Contact-invariant cost penalizes distortion and slip (difference between endpoint and surface, measured normal, and velocity relative to contact point)
      • Contact point is also 'soft' and smooth via distance-normalized weighting.
    • All contact forces are merged into a f 6 vector, which includes both forces and torques. Hence contact force origin can move within the contact patch, which again makes the optimization smoother.
    • Set τ(q,q˙,q¨)=J(q) Tf+Bu where J(q) T maps generalize (endpoint) velocities to contact-point velocities, and f above are the contact-forces. B is to map control forces u to the full space.
    • τ(q,q˙,q¨)=M(q)q˙+C(q,q˙)q˙+G(q) -- M is inertia matrix, C is Coriolis matrix, g is gravity.
      • This means: forces need to add to zero. (friction f + control u = inertia + coriolis + gravity)
    • Hence need to optimize f and u .
      • Use friction-cone approximation for non-grab (feet) contact forces.
    • These are optimized within a quadratic programming framework.
      • LBFGS algo.
      • Squared terms for friction and control, squared penalization for penetrating and slipping on a surface.
    • Phases of optimization (continuation method):
      • L(s)=L CI(s)+L physics(s)+L task(s)+L hint(s)
      • task term only: wishful thinking.
      • all 4 terms, physcics lessened -- gradually add constraints.
      • all terms, no hint, full physics.
  • Total time to simulate 2-10 minutes per clip (only!)
  • The equations of the paper seem incomplete -- not clear how QP eq fits in with the L(s) , and how c i fits in with J(q) Tf+Bu

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ref: -0 tags: ZeroMQ messaging sockets multithreading date: 05-03-2016 06:10 gmt revision:0 [head]

ZeroMQ -- much better sockets framework than native TCP/UDP sockets.

  • Bindings for Ocaml, too.
  • Supports Erlang-like concurrency.

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ref: -0 tags: molecule mean free path vacuum date: 05-01-2016 03:16 gmt revision:0 [head]

Useful numbers for estimating molecular mean-free-path in vacuum systems:

"

PressureTorrMean free path
0.01 Pa7.5e-5 torr4.8 m
10 Pa75 mTorr4.8 mm
30 Pa225 mTorr1.6 mm

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ref: -0 tags: google glucose sensing contact lens date: 04-28-2016 19:41 gmt revision:2 [1] [0] [head]

A contact lens with embedded sensor for monitoring tear glucose level

  • PMID-21257302
  • Metal stack: Ti 10nM / Pd 10nM / Pt 100nm.
  • on a 100um thick PET film.
  • A 30 µL glucose oxidase solution (10 mg/mL) was dropped onto the sensor area.
  • Then the sensor was suspended vertically above a titanium isopropoxide solution in a sealed dish for 6 h to create a GOD/titania sol-gel membrane, just as reported (Yu et al., 2003).
  • After forming the sol-gel membrane, a 30 µL aliquot of Nafion® solution was dropped onto the same area of the sensor, and allowed to dry in air for about 20 min.
  • Yet, the interference rejection from Nafion is imperfect; at 100uM concentrations, glucose is indistinguishable from ascorbic acid + lactate + urea.
  • Sensor drifts to 55% original performance after 4 days: figure 6
    • sensor was stored in a buffer @ 4C.
    • Probably OK for contact lenses, though.

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ref: -0 tags: concentation of monoamine dopamine serotonin and norepinephrine in the brain date: 04-28-2016 19:38 gmt revision:3 [2] [1] [0] [head]

What are the concentrations of the monoamines in the brain? (Purpose: estimate the required electrochemical sensing area & efficiency)

  • Dopamine: 100 uM - 1 mM local, extracellular.
    • PMID-17709119 The Yin and Yang of dopamine release: a new perspective.
  • Serotonin (5-HT): 100 ng/g, 0.5 uM, whole brain (not extracellular!).
  • Norepinephrine / noradrenaline: 400 nm/g, 2.4 uM, again whole brain.
    • PMID-11744005 An enriched environment increases noradrenaline concentration in the mouse brain.
    • Also has whole-brain extracts for DA and 5HT, roughly:
      • 1200 ng/g DA
      • 400 ng/g NE
      • 350 ng/g 5-HT
  • So, one could imagine ~100 uM transient concentrations for all 3 monoamines.

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ref: -0 tags: micro LEDS Buzaki silicon neural probes optogenetics date: 04-18-2016 18:00 gmt revision:0 [head]

PMID-26627311 Monolithically Integrated μLEDs on Silicon Neural Probes for High-Resolution Optogenetic Studies in Behaving Animals.

  • 12 uLEDs and 32 rec sites integrated into one probe.
  • InGaN monolithically integrated LEDs.
    • Si has ~ 5x higher thermal conductivity than sapphire, allowing better heat dissipation.
    • Use quantum-well epitaxial layers, 460nm emission, 5nm Ni / 5nm Au current injection w/ 75% transmittance @ design wavelength.
      • Think the n/p GaN epitaxy is done by an outside company, NOVAGAN.
    • Efficiency near 80% -- small LEDs have fewer defects!
    • SiO2 + ALD Al2O3 passivation.
    • 70um wide, 30um thick shanks.

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ref: -0 tags: deep reinforcement learning date: 04-12-2016 17:19 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

Prioritized experience replay

  • In general, experience replay can reduce the amount of experience required to learn, and replace it with more computation and more memory – which are often cheaper resources than the RL agent’s interactions with its environment.
  • Transitions (between states) may be more or less
    • surprising (does the system in question have a model of the environment? It does have a model of the state & action expected reward, as it's Q-learning.
    • redundant, or
    • task-relevant
  • Some sundry neuroscience links:
    • Sequences associated with rewards appear to be replayed more frequently (Atherton et al., 2015; Ólafsdóttir et al., 2015; Foster & Wilson, 2006). Experiences with high magnitude TD error also appear to be replayed more often (Singer & Frank, 2009 PMID-20064396 ; McNamara et al., 2014).
  • Pose a useful example where the task is to learn (effectively) a random series of bits -- 'Blind Cliffwalk'. By choosing the replayed experiences properly (via an oracle), you can get an exponential speedup in learning.
  • Prioritized replay introduces bias because it changes [the sampled state-action] distribution in an uncontrolled fashion, and therefore changes the solution that the estimates will converge to (even if the policy and state distribution are fixed). We can correct this bias by using importance-sampling (IS) weights.
    • These weights are the inverse of the priority weights, but don't matter so much at the beginning, when things are more stochastic; they anneal the controlling exponent.
  • There are two ways of selecting (weighting) the priority weights:
    • Direct, proportional to the TD-error encountered when visiting a sequence.
    • Ranked, where errors and sequences are stored in a data structure ordered based on error and sampled 1/rank .
  • Somewhat illuminating is how the deep TD or Q learning is unable to even scratch the surface of Tetris or Montezuma's Revenge.

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ref: -0 tags: delete date: 03-26-2016 07:42 gmt revision:1 [0] [head]

select * from sys.tables

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ref: -0 tags: meta compilation self-hostying ACM date: 12-30-2015 07:52 gmt revision:2 [1] [0] [head]

META II: Digital Vellum in the Digital Scriptorium: Revisiting Schorre's 1962 compiler-compiler

  • Provides high-level commentary about re-implementing the META-II self-reproducing compiler, using Python as a backend, and mountain climbing as an analogy. Good read.
  • Original paper
  • What it means to be self-reproducing: The original compiler was written in assembly (in this case, a bytecode assembly). When this compiler is run and fed the language description (figure 5 in the paper), it outputs bytecode which is identical (or almost nearly so) to the hand-coded compiler. When this automatically-generated compiler is run and fed the language description (again!) it reproduces itself (same bytecode) perfectly.
    • See section "How the Meta II compiler was written"

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ref: Linsmeier-2011.01 tags: histology lund electrodes immune response fine flexible review Thelin date: 12-08-2015 23:57 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

PMID-21867803[0] Can histology solve the riddle of the nonfunctioning electrode? Factors influencing the biocompatibility of brain machine interfaces.

  • We show results from an ultrathin multichannel wire electrode that has been implanted in the rat cerebral cortex for 1 year.
    • 12um Pt-Ir wires in a 200um bundle coated with gelatin. See PMID-20551508[1]
    • Electrode was left in the rat cortex for 354 days
    • no clear GFAP staining or ED1 positive cells at the electrode tips.
  • To improve biocompatibility of implanted electrodes, we would like to suggest that free-floating, very small, flexible, and, in time, wireless electrodes would elicit a diminished cell encapsulation.
  • Suggest standardized methods for the electrode design, the electrode implantation method, and the analyses of cell reactions after implantation
  • somewhat of a review -- Stice, Biran 2005 [2] 2007 [3].
  • 50um is the recording distance Purcell 2009.
  • See also [4]
  • Study of neuronal density and ED1 reactivity / GFAP:
    • Even at 12 weeks the correlation between NeuN density and GFAP / ED1 was small -- r 2=0.12
    • Note that DAPI labels many unknown cells in the vicinity of the electrode.

____References____

[0] Linsmeier CE, Thelin J, Danielsen N, Can histology solve the riddle of the nonfunctioning electrode? Factors influencing the biocompatibility of brain machine interfaces.Prog Brain Res 194no Issue 181-9 (2011)
[1] Lind G, Linsmeier CE, Thelin J, Schouenborg J, Gelatine-embedded electrodes--a novel biocompatible vehicle allowing implantation of highly flexible microelectrodes.J Neural Eng 7:4, 046005 (2010 Aug)
[2] Biran R, Martin DC, Tresco PA, Neuronal cell loss accompanies the brain tissue response to chronically implanted silicon microelectrode arrays.Exp Neurol 195:1, 115-26 (2005 Sep)
[3] Biran R, Martin DC, Tresco PA, The brain tissue response to implanted silicon microelectrode arrays is increased when the device is tethered to the skull.J Biomed Mater Res A 82:1, 169-78 (2007 Jul)
[4] Thelin J, Jörntell H, Psouni E, Garwicz M, Schouenborg J, Danielsen N, Linsmeier CE, Implant size and fixation mode strongly influence tissue reactions in the CNS.PLoS One 6:1, e16267 (2011 Jan 26)

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ref: -0 tags: alumina utah array electrode parylene encapsulation date: 10-23-2015 21:28 gmt revision:1 [0] [head]

Utah/blackrock group has been working on improving the longevity of their parlyene encapsulation with the addition of ~50nm Al2O3.

  • PMID-24771981 '''Self-aligned tip deinsulation of atomic layer deposited Al2O3 and parylene C coated Utah electrode array based neural interfaces
    • Process:
      • Normal Utah array dicing saw / glass frit / thinning and etch fabrication for the Utah probe.
      • Sputtered Ti, Sputtered Pt. (not sure how they mask this?)
      • Sputtered iridium oxide (SIROF, sputtered in an Ar + O2 plasma) electrode tips (again, not sure about the mask..)
      • ALD Al2O3 passivation, 50nm. Cambridge Fiji system, same as nanolab. Must take a long time!
      • A-174, aka 3-Methacryloxypropyltrimethoxysilane adhesion promoter (which presumably acts by pulling hydroxy groups off the alumina substrate; Al-O bonds have higher energy than Si-O)
      • 6um parylene.
      • Laser ablation of tips with 1000 pulses from KrF 5ns 100Hz excimer laser. Works much better than poking the electrode tips through thin aluminum foil.
      • O2 plasma descum / removal of carbon residues.
      • BOE removal of Al2O3 above the SIROF
    • Of note, ALD Al2O3 has included hydroxy bonds, which means that it gradually etches in PBS. (Pure Al2O3, as passivates aluminum parts exposed to seawater, does not?)
    • PBS also etches Si3N4, and crystaline Si.
  • IEEE-6627006 (pdf) Bi-layer encapsulation of utah array based neural interfaces by atomic layer deposited Al2O3 and parylene C
    • Atomic layer deposited (ALD) alumina is an excellent moisture barrier with WVTR at the order of ~ 10e-10 g·mm/m2·day [10-13]. But alumina alone is not suitable for encapsulation since it dissolves in water [14].
    • Demonstrated stable power-up of RF encapsulated devices for up to 600 equivalent days in 37C PBS.
      • Actual testing carried out at 57C, 4x accelerated.
  • PMID-24658358 Long-term reliability of Al2O3 and Parylene C bilayer encapsulated Utah electrode array based neural interfaces for chronic implantation.
    • Demonstrated good barrier longevity with wired Utah probes, active probes with flip-chip (Au/Sn eutectic reflow) record/stimulate circuits, and ones with bonded RF stimulation chips, INIR-6. (6th version!)
    • PBS etching of Si lead to undercutting & eventual flake-off of the SIROF, leading to dramatic impedance increase. (Figure 5 and 7).
      • no Pt under the SIROF?

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ref: -0 tags: reactive oxygen accelerated aging neural implants date: 10-07-2015 18:45 gmt revision:1 [0] [head]

PMID-25627426 Rapid evaluation of the durability of cortical neural implants using accelerated aging with reactive oxygen species.

  • Takmakov P1, Ruda K, Scott Phillips K, Isayeva IS, Krauthamer V, Welle CG.
  • TDT W / PI implants completely failed (W etched and PI completely flaked off) after 1 week in 87C H2O2 / PBS solution. Not surprising.
    • In the Au plated W, the Au remained, the PI flaked off, while thin fragile gold tubes were left. Interesting.
  • Pt/Ii + Parylene-C microprobes seemed to fare better; one was unaffected, others experienced a drop in impedance.
  • NeuralNexus (Si3N4 insulated, probably, plus Ir recording pads) showed no change in H2O2 RAA, strong impedance drop (thicker oxide layer?)
  • Same for blackrock / utah probe (Parylene-C), though there the parylene peeled from the Si substrate a bit.

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ref: -0 tags: street fighting mathematics Sanjoy Mahajan date: 10-04-2015 23:09 gmt revision:0 [head]

https://mitpress.mit.edu/sites/default/files/titles/free_download/9780262514293_Street_Fighting_Mathematics.pdf

https://mitpress.mit.edu/sites/default/files/titles/free_download/9780262526548_Art_of_Insight.pdf

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ref: -0 tags: third harmonic generation Nd:YAG pulsed laser date: 08-29-2015 06:44 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

Problem: have a Q-switched Nd:YAG laser, (flashlamp pumped, passively Q-switched) from ebay (see this album). Allegedly it outputs 1J pulses of 8ns duration; in practice, it may put several 100mJ pulses ~ 16ns long while the flashlamp is firing. It was sold as a tattoo removal machine. However, I'm employing it to drill micro-vias in fine polyimide films.

When focused through a 10x objective via the camera mount of an Leica microscope, 532nm (KTP doubled, second harmonic generation (SHG)) laser pulses both ablates the material, but does not leave a clean, sharp hole: it looks more like 'blasting': the hole is ragged, more like a crater. This may be from excessive 1064nm heating (partial KTP conversion), or plasma/flame heating & expansion due to absorption of the 532nm / 1064nm light. It may also be due to excessive pulse duration (should the laser not actually be q-switched... photodiode testing suggests otherwise, but I'd like to verify that), excessive pulse power, insufficient pulse intensity, or insufficient polyimide absorption at 532nm.

The solution to excessive plasma and insufficient polyimide absorption is to shift the wavelength to 355nm (NUV) via third harmonic generation, 1064 + 532 = 355nm. This requires sum frequency generation (SFG), for which LBO (lithium triborate) or BBO (beta-barium borate) seem the commonly accepted nonlinear optical materials.

To get SHG or THG, phase and polarization matching of the incoming light is critical. The output of the Nd:YAG laser is, I assume, non-polarized (or randomly polarized), as the KTP crystal simply screws on the front, and so should be rotationally agnostic (and there are no polarizing elements in the simple laser head -- unless the (presumed) Cr:YAG passive Q-switch induces some polarization.)

Output polarization of the KTP crystal will be perpendicular to the incoming beam; if the resulting THG / SFG crystal needs Type-1 phase matching (both in phase and parallel polarization), will need a half-wave plate for 1064nm; for Type-II phase matching, no plate is needed. For noncritical phase matching in LBO (which I just bought), an oven is required to heat the crystal to the correct temperature.

This suggests 73C for THG, while this suggests 150C (for SHG?).

Third harmonic frequency generation by type-I critically phase-matched LiB3O5 crystal by means of optically active quartz crystal Suggests most lasers operate in Type-1 SHG, and Type-II THG, but this is less efficient than dual Type-1; the quartz crystal is employed to rotate the polarizations to alignment. Both SHG and THG crystals are heated for optimum power output.

Finally, Short pulse duration of an extracavity sum-frequency mixing with an LiB3O5 (LBO) crystal suggests that no polarization change is required, nor oven control LBO temperature. Tight focus and high energy density is required, of course (at the expense of reduced crystal lifetime). Likely this is the Type-1,Type-II scheme alluded to in the paper above. I'll try this first before engaging further complexity (efficiency is not very important, as the holes are very small & material removal may be slow.)

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ref: -0 tags: polyimide adhesion delamination Stieglitz date: 08-18-2015 22:19 gmt revision:1 [0] [head]

Thin films and microelectrode arrays for neuroprosthetics

  • Juan Ordonez, Martin Schuettler, Christian Boehler, Tim Boretius and Thomas Stieglitz
  • Discussion of adhesion & ideas of using siliconcarbides as opposed to adhesion promoters (Silane A-174) to maintain good metal-polymer adhesion even with an equilibrium water vapor pressure.
  • Transition metals form carbide bonds with polyimide, but noble metals do not.
  • A one-metal (preferably noble) system is advantageous, as two metals will form a galvanic cell and eventually corrode.
  • Therefore it's best to develop non-metallic non-toxic adhesion promotion technologies.

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ref: -0 tags: berkeley airbears2 configuration linux debian 8.1 date: 08-13-2015 23:42 gmt revision:1 [0] [head]

{1322}
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ref: -0 tags: polyimide silicon carbide adhesion DBS syle electrodes date: 07-22-2015 18:01 gmt revision:0 [head]

PMID-25571176 Fabrication and characterization of a high-resolution neural probe for stereoelectroencephalography and single neuron recording.

  • Layer stack:
    • 5um PI (UBE U-varnish S)
    • 50nm SiC
      • Deposited at 100C.
    • 300nm Pt
    • 30nm SiC
    • 10nm DLC
    • 5um PI
      • Cured at 450C
    • 100nm Al hard mask (removed)
    • Cytop dry adhesion layer
      • softbake to remove solvent,
      • then hardbake at 290C for 4 hours to anneal the PI and adhere the Cytop to it.

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ref: -0 tags: delete date: 07-06-2015 04:22 gmt revision:2 [1] [0] [head]

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ref: -0 tags: delete date: 07-06-2015 04:22 gmt revision:2 [1] [0] [head]

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ref: -0 tags: polyimide epoxy potassium hydroxide etch adhesion date: 06-25-2015 00:28 gmt revision:0 [head]

Improvement in the adhesion of polyimide/epoxy joints using various curing agents

  • Used 1M KOH, ~2min, followed by 0.2M HCl for 6 min to ring-open the imide.
  • PMDA/ODA polyimide (Pyromellitic Dianhydride, single aromatic ring + 4,4 diamino diphenyl ether )
  • Epoxy of the DGEBA + linear amide or aromatic (3,3 methylenedianiline)
  • Best result was with a polyamide curing agent, and high-temp curing profile. Unlikely that this will work for us, parylene will decompose..

{1318}
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ref: -0 tags: standard enthalpy chemicals list pdf date: 06-25-2015 00:09 gmt revision:1 [0] [head]

Standard thermodynamic properties of chemical substances

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ref: -0 tags: tantalum chromium polyimide adhesion date: 06-24-2015 23:20 gmt revision:1 [0] [head]

Tantalum and chromium adhesion to polyimide. Part 2. Peel and locus of failure analyses

  • CF4 etch followed by Ar sputter yielded the strongest bond to the PI.
  • Suggest that failure may be within the PI (cohesive), not between the PI and metal (adhesive).

Tantalum, tantalum nitride, and chromium adhesion to polyimide: effect of annealing ambient on adhesion

  • The peel adhesion at T-0 (initial) shows the following order: TaNx∼ TaN < Ta∼ Cr, with all samples failing in apparently virgin PI.
  • After ten thermal cycles to 400°C
    • in forming gas the peel adhesion showed the following trend: TaNx < TaN∼ Ta ∼ Cr,
    • whereas if the annealing was done in N2 the order changed to TaNx∼ TaN « Ta < Cr.
  • The peel locus of failure was
    • always in the apparently virgin PI in the Cr/PI samples,
    • while the Ta/PI samples failed in the modified PI,
    • and the TaN/PI and TaNx/PI samples failed between the Ta-nitride and the Cu peel backing film after thermal cycling.

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ref: -0 tags: polyimide adhesion chromium copper tie layer upilex date: 06-24-2015 23:14 gmt revision:3 [2] [1] [0] [head]

Adhesion Evaluation of Adhesiveless Metal/Polyimide Substrate for MCM and high density packaging

  • Adhesion degradation after thermal and humidity stresses can occur for a number of reasons.
    • Copper diffusion can promote adhesion loss at elevated temperatures and can be inhibited by coating a barrier layer of metal – tie layer2.
    • Oxygen diffusion through polyimide film to the metal/polyimide interface plays a critical role in promoting degradation too3. Adhesion of Cr/polyimide interface is degraded significantly upon exposure to high temperature and humidity environment due to the hydrolysis of polyimide4,5 .
    • Catastrophic adhesion loss has been linked to moisture induced oxidation of chromium interfaces based on studies using radioactively tagged water4, 5.
  • That said, most of these vendors use Cr (20nm) as and adhesion layer, and Cu (200nm) as the conductor.
  • Upilex A faired very well after the pressure cooker test -- > 60% retention after 192 hours.
  • Seemingly Ta and Cr both adhere similarly to PI -- {1317}
    • Though Ta is much more ductile, and forms a stronger carbide, Cr is preferred... cheaper?

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ref: -2008 tags: tantalum chromium polyimide tungsten flexible neural implants adhesion layer date: 06-24-2015 22:53 gmt revision:2 [1] [0] [head]

PMID-18640155 Characterization of flexible ECoG electrode arrays for chronic recording in awake rats.

  • Yeager JD1, Phillips DJ, Rector DM, Bahr DF.
  • We tested several different adhesion techniques including the following: gold alone without an adhesion layer, titanium-tungsten, tantalum and chromium.
  • All films were DC magnetron sputtered, without breaking vacuum between the adhesion layer (5nm) and gold counductor layer (300nm).
  • We found titanium-tungsten to be a suitable adhesion layer considering the biocompatibility requirements as well as stability and delamination resistance.
  • While chromium and tantalum produced stronger gold adhesion, concerns over biocompatibility of these materials require further testing.
    • Thought: use tantalum directly, no Ti needed.
    • Much better than Cr -- much more ductile and biocompatible.
    • Caveat: studies showing reduction to stociometric Ta results in delamination.
  • Ta conductivity: 1.35e-7 Ohms * m; Ti 4.2e-7; 3x better (film can be 3x thinner..)

{1315}
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ref: -0 tags: adhesion polymer metal FTIR epoxy eponol paint date: 05-01-2015 19:20 gmt revision:0 [head]

Degradation of polymer/substrate interfaces – an attenuated total reflection Fourier transform infrared spectroscopy approach

  • Suggests why eponol is used as an additive to paint.
  • In this thesis, attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy has been used to detect changes at the interfaces between poly (vinyl butyral-co-vinyl alcohol-co-vinyl acetate) (PVB) and ZnSe upon exposure to ozone, humidity and UV-B light.
  • Also, the response of PVB-aluminum interfaces to liquid water has been studied and compared with the same for eponol (epoxy resin, diglycidyl ether of bisphenol A)-aluminum interfaces.
  • In the presence of ozone, humidity and UV-B radiation, an increase in carbonyl group intensity was observed at the PVB-ZnSe interface indicating structural degradation of the polymer near the interface. However, such changes were not observed when PVB coated ZnSe samples were exposed to moisture and UV-B light in the absence of ozone showing that ozone is responsible for the observed structural deterioration. Liquid water uptake kinetics for the degraded PVB monitored using ATR-FTIR indicated a degradation of the physical structural organization of the polymer film.
  • Exposure of PVB coated aluminum thin film to de-ionized water showed water incorporation at the interface. There were evidences for polymer swelling, delamination and corrosion of the aluminum film under the polymer layer.
    • On the contrary, delamination/swelling of the polymer was not observed at the eponol-aluminum interface, although water was still found to be incorporated at the interface. Al-O species were also observed to form beneath the polymer layer.
    • A decrease of the C-H intensities was detected at the PVB-aluminum interface during the water uptake of the polymer, whereas an increase of the C-H intensities was observed for the eponol polymer under these conditions.
    • This is assigned to rearrangement of the macromolecular polymer chains upon interaction with water.

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ref: -0 tags: Kewame carbon nanotube yarn wet spinning CNT date: 03-26-2015 18:29 gmt revision:0 [head]

Neural Stimulation and Recording with Bidirectional, Soft Carbon Nanotube Fiber Microelectrodes

  • 43um diameter CTN yarn
  • Shows superior charge injection / surface area.
  • polystyrene-polybutadiene co-polymer insulation (like ABS, without the acrylonitrile)
  • https://chemistry.beloit.edu/classes/nanotech/CNT/nanotoday3_5_24.pdf -- details on the process of spinning these CNT yarns.
    • Tensile strength still far below commercial carbon fibers or high-strength polymers.

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ref: -2005 tags: electric fish date: 03-24-2015 20:35 gmt revision:0 [head]

Central Neuroanatomy of Electrosensory Systems in Fish

  • See chapter 3, Morphology of Electroreceptive Sensory Organs, Jørgen Mørup Jørgensen
  • It seems that weakly electric fishes improve external field sensitivity by putting the sensory organs at the end of a sometimes long, conductive-mucus filled duct, surrounded by insulating/fatty/tight-junctioned epithelia, and that these sensory cells tend to have microvilli or other surface-area enhancements.
  • Interestingly, in both saltwater and freshwater, the limit of the most sensitive fishes seems to be the inherent noise of the weakly resistive environment -- saltwater fishes are ~10x more acute... I suspect the microvilli may be to combat noise.
  • That said, the duck-billed platypus' electrosensory organs are bare sensory neurons (still at the end of ducts), with a sensitivity of 20-200uV/cm (best saltwater fishes are 1000x better) and a great many of fish seem to have evolved (and lost) electrosensation.

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ref: -2002 tags: electric catfish date: 03-24-2015 20:32 gmt revision:0 [head]

PMID-11889591 Spontaneous nerve activity and sensitivity in catfish ampullary electroreceptor organs after tetanus toxin application

  • M. Struik,F. Bretschneider,R. Peters 2002
  • Applied TTX to catfish electrosensitive skin & measured spontaneous and evoked afferent responses.
  • The results show that TeTx reduces sensitivity to less then 20% of its original value, whereas the spontaneous activity is unaffected by the treatment. This indicates that the afferent nerve is capable of generating impulses independent of receptor cell neurotransmitter release.
    • Might mean that the amplifying ion channel is Na-permeable?

{1309}
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ref: -0 tags: electric fish date: 03-24-2015 20:14 gmt revision:2 [1] [0] [head]

The physiology of low-frequency electrosensory systems

  • D Bodznick, JC Montgomery - Electroreception
  • In (teleost) ampullary electroreceptors sensory transduction is direct and accomplished by voltage-gated Ca channels in the receptor cell membranes. It is natural to think that extraordinary receptor sensitivity must require extraordinarily sensitive ion channels, but the pharmacology and electrical properties of summed receptor currents indicate that they are very similar to N and L type Ca channels (Sugawara 1989b; Lu and Fishman 1995 {1310}).
    • Instead, the high sensitivity of the electroreceptors appears to derive at least in part from (1) the elimination of response threshold by maintaining the receptor cells in a partially activated state or oscillating even in the absence of a stimulus, (2) DC synapses that also lack a threshold and steadily release transmitter as a function of membrane potential, and (3) a very large convergence ratio of receptor cells to afferent fibers. The structure of the receptor organs also plays a role by ensuring that nearly all the available stimulus potential is brought to bear directly across the sensory epithelium. The long canals in marine forms contribute particularly to sensitivity in shallow voltage gradients.
    • Teleost ampullary electroreceptors apparently evolved from lateral line mechanoreceptors and in each case the receptor cell basal membrane remains the voltage sensor while the apical membrane is passive and low resistance.
    • In Plotosus and probably other teleosts an electrogenic Na–K pump in the basal surface of the receptor epithelium provides a steady outward bias current across the sensory epithelium at rest (Sugawara 1989a). This current is set at a level to partially activate a noninactivating Ca conductance in the basal receptor cell membrane, and voltage-clamp measures show that the receptor epithelium sits in he negative slope conductance region of its summed I–V curve even at rest.
  • I find some of their explanation of the ionic currents to be loose and unclear; may stem from the fact that research is ongoing.

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ref: -0 tags: microflex interconnect polyimide Stieglitz date: 03-03-2015 00:33 gmt revision:1 [0] [head]

IEEE-938305 (pdf) High Density Interconnects and flexible hybrid assemblies for active biomedical implants

  • Idea: make vias in your metallized PI film. Bump-bond through these vias to a chip below.
  • Achieve center-to -center distances of 100um.
  • No longer using this? See {1250}, which uses thermosonic bonding.

{1308}
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ref: -0 tags: polyimide polyamide basic reduction salt surface modification date: 02-27-2015 19:45 gmt revision:0 [head]

Kinetics of Alkaline Hydrolysis of a Polyimide Surface

  • The alkaline hydrolysis of a polyimide (PMDA-ODA) surface was studied as a function of time, temperature and hydroxide ion concentration.
  • Quantification of the number of carboxylic acid groups formed on the modified polyimide surface was accomplished by analysis of data from contact angle titration experiments.
  • Using a large excess of base, pseudo-first-order kinetics were found, yielding kobs ≈ 0.1−0.9 min-1 for conversion of polyimide to poly(amic acid) depending on [OH-].
  • From the dependence of kobs on [OH-], a rate equation is proposed.
  • Conversion of the polyimide surface to one of poly(amic acid) was found to reach a limiting value with a formation constant, K, in the range 2−10 L·mol-1.

{1307}
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ref: -2000 tags: polyimide acrylic aluminum electro deposition imide insulation ultra thin date: 02-27-2015 19:42 gmt revision:0 [head]

Ultrathin, Layered Polyamide and Polyimide Coatings on Aluminum

  • Alternating polyelectrolyte deposition of layered poly(acrylic acid)/poly(allylamine hydrochloride) (PAA/PAH) films on Al produces ultrathin coatings that protect Al from Cl--induced corrosion.
  • Resistance goes from 5 MOhm/cm^2 at 10nm thickness to ~50MOhm/cm^2 following imidization of the monolayer-applied polymer films.

{1304}
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ref: -0 tags: gold carbon nanotube electroplating impedance PEG date: 10-24-2014 22:25 gmt revision:1 [0] [head]

PMID-21379404 Creating low-impedance tetrodes by electroplating with additives

  • Electroplated tetrodes to 30-70 kΩ by adding polyethylene glycol (PEG) or multi-walled carbon nanotube (MWCNT) solutions to a commercial gold-plating solution.
  • Cui and Martin [12] showed that altering the concentration of gold-plating solution and electroplating current can change the morphology of a gold-plated microelectrode coating.
  • Additionally, Keefer et al. [13] found that adding multi-walled carbon nanotubes (MWCNTs) to a gold-plating solution created microelectrode coatings with a “rice-like” texture and very low impedances.
  • Au electroplating solution made of non-cyanide, gold-plating solution (5355, SIFCO Selective Plating, Cleveland, OH).
  • A one-second, reversed-polarity pulse helped to clean the surface of the tetrode tip and lowered the impedances to 2MΩ to 3 MΩ before electroplating.
  • Electroplating pulses were one to five seconds long and were repeated until the tetrodes reached the desired impedances. After electroplating, the tetrodes were soaked in DI, air dried, and checked for shorts.

Conclusion: 75% PEG, commercial electropating solution, 0.1ua current pluses to 250K or less.

  • Though the Caswell Au plating solution will likely behave differently ..

{1303}
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ref: -0 tags: delete date: 10-11-2014 00:50 gmt revision:1 [0] [head]

  1. 1000A Oxide wafer, as purchased.
This makes PI release easy. Native, piranha / HF cleaned wafers are another option; will then require a heated bath soak & dehydrate prior parylene deposition. Unclear which is best; biased to the former.
  1. PI spin, bake 350C
  2. AR, N2, O2 plasma etch.
Need to run some tests to optimize adhesion protocol, as well as decide between Al and Ti.
  1. LOR-5A, I-line lift-off
though: others use G-line resist for Pd; perhaps it's more thermally resistant?
  1. Al - Pd - Au - Pd metalization.
Wait between layers to allow everything to cool down. Make the Al layer thicker to act as a stress buffer? (80nm?) Or try a thin layer of chromium -- 5nm should be fine. {1265} This is a temporary solution, as the Cr-PI interface is hydrolized gradually.
  1. If the adhesion is sufficient, can lift-off in the ultrasonicator, which saves time & reduces PI exposure to NMP.
In my experience, Cr makes this significantly easier. Otherwise, redesign the mask to make
  1. Dry. overnight + vacoven.
  2. Spin second layer of PI, cure 410C
  3. Etch contact sites -- both recording and bond.
  4. Lift-off to pattern recording sites
Worried that Pd may be oxidized by O2 plasma -> top layer should be Au. This will also serve to define the head geometry, and prevent excess etch w/ parylene. Add patterning in the mask to make the liftoff easier Add masking to stop parylene etch. Do this for entire outline? Would make etch significantly easier.
  1. Plasma process for de-scum & adhesion
  2. Evaporate second metal stack
Al - Pd - Au or Cr - Au or Ti - Au (since adhesion will not, at this point, be subject to ultrasonic energy).
  1. O2 plasma etch full device outlines
Should be sharp, since we'll have a full hard mask. That said: this may affect fiber release from parylene, due to slightly different sidewall profiles. Hence this step could be risky -- or could be beneficial, as we can soak indefinitely with only mechanical interlock.
  1. PR mask regions we want metal2 to stay
  2. Au & Ti etch other areas, leaving hard masks for parylene etch.
  3. HMDS application to make sure the resist stays securely.
  4. PR mask (thick!) areas not to be plated
This is to prevent NiSO4 / NaH2PO4 from releasing the electrodes prematurely. And to keep everything clean from the dirty Ni bath ** must be tested, perhaps on next wafer! **
  1. Ni plate to 10um
  2. Flash Au plate
This keeps O2 etch from oxidizing Ni & prevents parlene from sticking to the Ni.
  1. PR protect vital bonding sites (optional?)
  2. Plasma descum of any residual HMDS
  3. Parylene dep, 3-5um
  4. SPR-220-7 thick resist, 10um
  5. O2 etch to pattern parylene.
But not over the bondpad sites!! Parylene scum messes with both wirebonding and ACF bonding.
  1. Removal of parylene over bondpad sites -- before taking off the wafer. Clean in acetone.
  2. Removal of electrodes from wafer using water (bonding area) then IPA (electrode shank), clean protection PR in acetone.
Removal should be easy from 1000A SiO2 wafers.
  1. Bond to cartridges
  2. Soak in water 24 hours to lessen PI-parylene adhesion.

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ref: -0 tags: kevlar electrodes flexible polymer 12um McNaughton Utah date: 10-11-2014 00:19 gmt revision:0 [head]

PMID-8982987 Metallized polymer fibers as leadwires and intrafascicular microelectrodes

  • McNaughton TG1, Horch KW.
  • Ti/W, Au, Pt metalization via sputtering.
  • 12um core diamater.
  • demonstrate 8 month reliability.
  • 1um dipped silicone elastomer insulation.
  • note difficulty in manufactuing the fibers. No kidding!
  • Tensile strength the same as a 25um Pt-Ir wire, 90x more flexible.

{1265}
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ref: -0 tags: nickel chrome polyimide adhesion date: 10-11-2014 00:13 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

Adhesiveless copper on polyimide substrate with nickel-chromium tiecoat

  • Chrome works the best, with Nichrome lagging slightly behind. Thicker tie layers (20nm) work slightly better.
  • 17 nm Cr and 5nm NiCr both work well after gold plating
    • in aggressive cyanide solution -- without tie layer, the copper was released.
    • note how thin the layers are!
  • Surface benefits from oxygen plasma pre-treatment. (de-scum?)
  • Still not sure how to get second layer of polyimide to adhere to top layer of Cr.

Adhesion Between Polymers and Other Substances - A Review of Bonding Mechanisms, Systems and Testing

  • The adhesion between the polyimide, PMDA-ODA and metals such as copper or chromium has received considerable attention due to its importance in the microelectronics industries.
  • As mentioned, the PMDA-ODA is normally deposited from solution as the polyamic acid and cured in-situ to the imide form.
  • Adhesion of the polyimide deposited on a metal is therefore a different problem than adhesion of a metal deposited on the cured polyimide.
  • The former situation (polyimide on metal) tends to give stronger adhesion than the latter (metal on polyimide) but there can be problems of metal, particularly copper, dissolution.
  • Great! (is this a reliable source?)
  • The interaction between the metals and the polyimide has been studied in great detail using x-ray photoelectron spectroscopy (XPS) and other surface analysis techniques but there is not complete agreement on the form of the interaction.
    • It is clear that strong interaction and electron transfer occurs when the metal is deposited from vapour onto the polyimide.
    • When the polyamic acid is deposited on the metal and cured then reaction occurs between the acid and the metal.
  • The strong interface formed between chromium and the polyimide is clearly a result of the strong chemical interaction but there is still considerable interest in making it more resistant to water and oxidation.

High-Performance Polymers (book) Guy Rabilloud (via google books.)

  • Order of metals by increasing adhesion:
    • Cu, Pd, Ni, V, Cr, Nb, Ti [140]
  • The adhesion between chromium and polyimide is degraded sharply as the interface is exposed to temperature-humidity stressing (85C, 81% RH [612]
  • Polyimide-polyimide self-adhesion strongly benefits from partial cure of the first layer (which is not possible with lithographic processes, TMAH etches uncured film). Plasma and adhesion treatments would likely help, due to molecular tangling (?). Presumably VM-651 helps. We'll cross that bridge when we get to it.
  • PMDA-PPD or PMDA-PDA is perhaps the most rigid of all the polyimides, but due to the extremely hydrophillic nature of PMDA & associated electron affinity of the dianhydride ( E a ), and the fact that it tends to crystalize & not be tough/plastic, it's infrequently used.

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ref: -0 tags: polybenzoxazole PBO synthesis zylon date: 10-10-2014 22:40 gmt revision:0 [head]

Synthesis and thermal properties of polybenzoxazole from soluble precursors with hydroxy-substituted polyenaminonitrile

  • Process:
    1. purified/distilled reagents
    2. made the CCB, a open-ring soluble precursor
    3. eluted the CCB in water / methanol
    4. thermoset the resulting polymer.
  • No control of molecular weight, nor material properties of the cured film.
  • Resultant film was highly temperature resistant, though.

{1300}
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ref: -0 tags: Peter Ledochowitsch ECoG parylene fabrication MEMS date: 09-25-2014 16:54 gmt revision:0 [head]

IEEE-5734604 (pdf) Fabrication and testing of a large area, high density, parylene MEMS µECoG array

  • Details 5-layer platinum parylene process for high density ECoG arrays.

{1299}
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ref: -0 tags: wirebonding finishes gold nickel palladium electroless electrolytic date: 09-21-2014 02:53 gmt revision:3 [2] [1] [0] [head]

Why palladium?


To prevent black nickel: http://tayloredge.com/reference/Electronics/PWB/BlackPad_ITRI_Round1.PD

Introduction The use of electroless nickel / immersion gold (E.Ni/I.Au) as a circuit board finish has grown significantly in the last few years. It provides a flat board finish, is very solderable, provides a precious metal contact surface and the nickel strengthens the plated holes. However, as the usage of E.Ni/I.Au increased, a problem was found on BGA (Ball Grid Array) components. An open or fractured solder joint sometimes appears after board assembly on the occasional BGA pad. The solder had wet and dissolved the gold and formed a weak intermetallic bond to the nickel. This weak bond to the nickel readily fractures under stress or shock, leaving an open circuit. The incidence of this problem appears to be very sporadic and a low ppm level problem, but it is very unpredictable. A BGA solder joint cannot be touched-up without the component being removed. After the BGA component is removed, a black pad is observed at the affected pad site. This black pad is not readily solderable, but it can be repaired.


From: http://www.smtnet.com/Forums/index.cfm?fuseaction=view_thread&Thread_ID=4430

You don't have enough gold. Your 2uin is too porous and is allowing the nickel to corrode. Prove that this by hand soldering to these pads with a more active flux, like a water soluble solder paste, than you are using.

You must have at least 3uin of immersion gold. Seriously consider >5uin.

Your nickel thickness is fine. Although if you wanted to trade costs, consider giving-up nickel to 150uin thickness, while increasing the gold thickness. Gold over electroless nickel creates brittle joints because of phosphorous in the nickel plating bath. The phosphorous migrates into the over-plating. Electrolytic nickel and gold plating should not be a problem.

If you stay with the electroless nickel, keep the phosphorous at a mid [7 - 9%] level. Just as important, don't let the immersion gold get too aggressive. The immersion gold works by corroding the nickel. If it is too aggressive it takes away the nickel and leave phosphorous behind. This makes it look like the phosphorous level is too high in the nickel bath.

Gold purity is very important for any type of wire bonding process. For aluminum wedge bonding, gold should have a purity of 99. 99% [no thalium] and the nickel becomes critical. No contaminates and the nickel wants to be plated a soft as possible. This requires good control of Ph and plating chemicals in the nickel-plating bath.

Harman "Wire Bonding In Microelectronics" McGraw-Hill is a good resource for troubleshooting wire bonding. I reviewed it in the SMTnet Newsletter a couple of months ago.


That said, electrolytic nickel + electrolytic gold does work well -- perhaps even better than ENEPIG:

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ref: -0 tags: RF microstimulation cats threshold date: 09-04-2014 18:43 gmt revision:1 [0] [head]

PMID-13539663 Subcortical threshold voltages as a function of sine wave frequencies Brown and Brackett

  • 22 GA insulated stainless steel electrodes, both bipolar and monopolar.
    • This happens to be near spike recording passband, unfortunately.
  • Square wave stimulation (8) Mihailovic and Delgado 1956 "Electrical stimulation of monkey brain with various frequencies and pulse durations".
  • Hines (6)(1940) , stimulating the monkey cortex with [a] sine wave, reported jerky uncompleted movements from 1260 Hz to 1440 Hz.
    • Monopolar surface stimulation, though.

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ref: Cosman-2005.12 tags: microstimulation RF pain neural tissue ICMS date: 09-04-2014 18:10 gmt revision:14 [13] [12] [11] [10] [9] [8] [head]

One of the goals/needs of the lab is to be able to stimluate and record nervous tissue at the same time. We do not have immediate access to optogenetic methods, but what about lower frequency EM stimulation? The idea: if you put the stimulation frequency outside the recording system bandwidth, there is no need to switch, and indeed no reason you can't stimulate and record at the same time.

Hence, I very briefly checked for the effects of RF stimulation on nervous tissue.

  • PMID-16336478[0] Electric and Thermal Field Effects in Tissue Around Radiofrequency Electrodes
    • Most clinical response to pulsed RF is heat ablation - the RF pulses can generate 'hot spots' c.f. continuous RF.
    • Secondary effect may be electroporation; this is not extensively investigation.
    • Suggests that 500kHz pulses can be 'rectified' by the membrane, and hence induce sodium influx, hence neuron activation.
    • They propose that some of the clinical effects of pulsed RF stimulation is mediated through LTD response.
  • {1297} -- original!
  • PMID-14206843[2] Electrical Stimulation of Excitable Tissue by Radio-Frequency Transmission
    • Actually not so interesting -- deals with RF powered pacemakers and bladder stimulators; both which include rectification.
  • Pulsed and Continous Radiofrequency Current Adjacent to the Cervical Dorsal Root Ganglion of the Rat Induces Late Cellular Activity in the Dorsal Horn
    • shows that neurons are activated by pulsed RF, albeit through c-Fos staining. Electrodes were much larger in this study.
    • Also see PMID-15618777[3] associated editorial which calls for more extensive clinical, controlled testing. The editorial gives some very interesting personal details - scientists from the former Soviet bloc!
  • PMID-16310722[4] Pulsed radiofrequency applied to dorsal root ganglia causes a selective increase in ATF3 in small neurons.
    • used 20ms pulses of 500kHz.
    • Small diameter fibers are differentially activated.
    • Pulsed RF induces activating transcription factor 3 (ATF3), which has been used as an indicator of cellular stress in a variety of tissues.
    • However, there were no particular signs of axonal damage; hence the clinically effective analgesia may be reflective of a decrease in cell activity, synaptic release (or general cell health?)
    • Implies that RF may be dangerous below levels that cause tissue heating.
  • Cellphone Radiation Increases Brain Activity
    • Implies that Rf energy - here presumably in 800-900Mhz or 1800-1900Mhz - is capable of exciting nervous tissue without electroporation.
  • Random idea: I wonder if it is possible to get a more active signal out of an electrode by stimulating with RF? (simultaneously?)
  • Human auditory perception of pulsed radiofrequency energy
    • Evicence seems to support the theory that it is local slight heating -- 6e-5 C -- that creates pressure waves which can be heard by humans, guinea pigs, etc.
    • Unlikely to be direct neural stimulation.
    • High frequency hearing is required for this
      • Perhaps because it is lower harmonics of thead resonance that are heard (??).

Conclusion: worth a shot, especially given the paper by Alberts et al 1972.

  • There should be a frequency that sodium channels react to, without inducing cellular stress.
  • Must be very careful to not heat the tissue - need a power controlled RF stimulator
    • The studies above seem to work with voltage-control (?!)

____References____

[0] Cosman ER Jr, Cosman ER Sr, Electric and thermal field effects in tissue around radiofrequency electrodes.Pain Med 6:6, 405-24 (2005 Nov-Dec)
[1] Alberts WW, Wright EW Jr, Feinstein B, Gleason CA, Sensory responses elicited by subcortical high frequency electrical stimulation in man.J Neurosurg 36:1, 80-2 (1972 Jan)
[2] GLENN WW, HAGEMAN JH, MAURO A, EISENBERG L, FLANIGAN S, HARVARD M, ELECTRICAL STIMULATION OF EXCITABLE TISSUE BY RADIO-FREQUENCY TRANSMISSION.Ann Surg 160no Issue 338-50 (1964 Sep)
[3] Richebé P, Rathmell JP, Brennan TJ, Immediate early genes after pulsed radiofrequency treatment: neurobiology in need of clinical trials.Anesthesiology 102:1, 1-3 (2005 Jan)
[4] Hamann W, Abou-Sherif S, Thompson S, Hall S, Pulsed radiofrequency applied to dorsal root ganglia causes a selective increase in ATF3 in small neurons.Eur J Pain 10:2, 171-6 (2006 Feb)

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ref: -0 tags: physical principles of scalable neural recording marblestone date: 08-25-2014 20:21 gmt revision:0 [head]

PMID-24187539 Physical principles for scalable neural recording.

  • Marblestone AH1, Zamft BM, Maguire YG, Shapiro MG, Cybulski TR, Glaser JI, Amodei D, Stranges PB, Kalhor R, Dalrymple DA, Seo D, Alon E, Maharbiz MM, Carmena JM, Rabaey JM, Boyden ES, Church GM, Kording KP.

{1295}
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ref: -0 tags: hike tamalpais kent lake california date: 08-24-2014 19:17 gmt revision:1 [0] [head]

Pretty solid hike yesterday. 25.25 miles (or likely more, given the limited resolution of my tracing) in about 7.5 hours for an average speed of 3.4 mph. Lots of different terrain and eosystems along the way -- redwoods to lakeside to golden grassy hilltops to manzanita / scrub forest. Would be good for mountain biking.

{1292}
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ref: -0 tags: intracortical utah array fabrication MEMS Normann date: 08-14-2014 01:35 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-1937509 A silicon-based, three-dimensional neural interface: manufacturing processes for an intracortical electrode array.

  • Campbell PK1, Jones KE, Huber RJ, Horch KW, Normann RA. (1991)
  • One of (but not the) first papers describing their methods / idea (I think).
  • First conf paper: {1294} (1988)
  • later adopted glass frit insulator --

{1294}
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ref: -0 tags: utah array development date: 08-14-2014 01:34 gmt revision:1 [0] [head]

IEEE-94953 (pdf) Silicon based microstructures suitable for intracortical electrical stimulation (visual prosthesis application)

  • Normann, R.A. ; Dept. of Bioeng., Utah Univ., Salt Lake City, UT, USA ; Campbell, P.K. ; Li, W.P.
  • 1988
  • not quite yet there...

{1293}
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ref: -0 tags: utah array development failure mode donoghue date: 08-14-2014 01:30 gmt revision:0 [head]

PMID-24216311 Failure mode analysis of silicon-based intracortical microelectrode arrays in non-human primates

  • Barrese JC, Rao N, Paroo K, Triebwasser C, Vargas-Irwin C, Franquemont L, Donoghue JP. (2013)
  • Most failures (56%) occurred within a year of implantation, with acute mechanical failures the most common class (48%), largely because of connector issues (83%).
  • Among grossly observable biological failures (24%), a progressive meningeal reaction that separated the array from the parenchyma was most prevalent (14.5%).

{1212}
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ref: Nordhausen-1994.02 tags: Utah array electrodes optimization date: 08-14-2014 01:24 gmt revision:2 [1] [0] [head]

PMID-8180807[0] Optimizing recording capabilities of the Utah Intracortical Electrode Array.

  • Nordhausen, Rousch, Normann (1993)
  • Originally it was designed for stimulation in a visual prosthesis.
  • Thought that the large surface area would securely anchor it to the cortex
    • Turns out you need to put gore-tex on top to keep it from being expelled.
  • Varied the exposed electrode tip to determine the optimum area.
  • Oldschool computer plots ...

____References____

[0] Nordhausen CT, Rousche PJ, Normann RA, Optimizing recording capabilities of the Utah Intracortical Electrode Array.Brain Res 637:1-2, 27-36 (1994 Feb 21)

{1291}
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ref: -0 tags: tungsten welding CVD arc braze 1971 date: 08-12-2014 20:56 gmt revision:0 [head]

Weldability of Tungsten and Its Alloys

  • tried relatively exotic brazing methods:
    • Niobium,
    • Tantalum
    • W - 26% Re
    • Mo
      • No mention of what we'll be doing (NiCr resistance wire -- only easily available fine wire)
  • Note that the ductile-to-brittle transition is low for their samples, 150-250C.
  • Samples made via arc-melting or WF + H2 CVD.

{1112}
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ref: Seymour-2011.06 tags: PEDOT Seymour electrode recording parylene date: 08-06-2014 22:39 gmt revision:3 [2] [1] [0] [head]

PMID-21301965[0] Novel multi-sided, microelectrode arrays for implantable neural applications.

  • There are problems with parylene multielectrode arrays:
    • water and salts will rapidly diffuse into the various interfacial boundaries
    • Interfacial delamination due to poor wet adhesion of parylene on metal
      • This possibly due to mechanical stress
      • causes excessive cross-talk or noise.
    • Parylene-C devices are prone to poor adhesion at either the dielectric to dielectric interface or at the dielectric to metal interface *** (Sharma and Yasuda 1982; Yasuda et al 2001)
  • solution: PPXCH 2NH 2 and PPXCHO -- reactive parylene (amine bonds?!)
  • PEDOT is absolutely essential for attaining reasonable performance / impedance from the 85um^2 gold electrodes.
    • Thermal noise on 280um^2 and 170um^2 Au electrodes was too high to record neurons.
    • AU thickness 0.5um.
  • Performed soak tests on their electrodes; the reactive parylene is good, but not sure if it's a worthy improvement.

____References____

[0] Seymour JP, Langhals NB, Anderson DJ, Kipke DR, Novel multi-sided, microelectrode arrays for implantable neural applications.Biomed Microdevices 13:3, 441-51 (2011 Jun)

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ref: -0 tags: neurite growth factor NGF 1977 date: 08-05-2014 23:02 gmt revision:0 [head]

PMID-270699 Local control of neurite development by nerve growth factor.

  • After neurites crossed the barrier (fluid barrier to NGF), local removal of nerve growth factor from the distal portions of the neurites caused the growth of these portions to stop, and they eventually appeared to degenerate even though nerve growth factor was continuously present in the chamber that contained their somas and proximal portions.
  • In contrast, local nerve growth factor was not required at the somas and proximal portions of the neurites; many neurons survived its withdrawal provided their somas were associated with neurite bundles that crossed into a chamber containing nerve growth factor.

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ref: -0 tags: debugging reinvented java CMU code profiling instrumentation date: 08-02-2014 06:32 gmt revision:3 [2] [1] [0] [head]

images/1289_1.pdf -- Debugging reinvented: Asking and Answering Why and Why not Questions about Program Behavior.

  • Smart approach to allow users to quickly find the causes of bugs (or more generically, any program actions).

{1288}
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ref: -0 tags: automatic programming inductive functional igor date: 07-29-2014 02:07 gmt revision:0 [head]

Inductive Rule Learning on the Knowledge Level.

  • 2011.
  • v2 of their IGOR inductive-synthesis program.
  • Quote: The general idea of learning domain specific problem solving strategies is that first some small sample problems are solved by means of some planning or problem solving algorithm and that then a set of generalized rules are learned from this sample experience. This set of rules represents the competence to solve arbitrary problems in this domain.
  • My take is that, rather than using heuristic search to discover programs by testing specifications, they use memories of the output to select programs directly (?)
    • This is allegedly a compromise between the generate-and-test and analytic strategies.
  • Description is couched in CS-lingo which I am inexperienced in, and is perhaps too high-level, a sin I too am at times guilty of.
  • It seems like a good idea, though the examples are rather unimpressive as compared to MagicHaskeller.

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ref: -0 tags: polyimide anodic release 2005 date: 06-16-2014 23:58 gmt revision:1 [0] [head]

IEEE-1416914 (pdf) Partial release and detachment of microfabricated metal and polymer structures by anodic metal dissolution

  • recommend 100nm Cr/Al release layer.
  • finished devices just 'float to the surface' of saline solution.

{1276}
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ref: -0 tags: polyimide silicon oxide aluminum adhesion pressure cooker date: 06-16-2014 21:28 gmt revision:2 [1] [0] [head]

Interfacial adhesion of polymeric coatings for microelectronic encapsulation

  • Find that, after a pressure-cooker test, adhesion of polyimide PI-2610 (what we use) to SiO2 was weaker than to Al, SiN, and copper.
  • Aluminum adhesion is quite good, at least to (only) 15 days @ 85C / 85% RH. Reference studies that find the adhesion to be 'acceptable' for the microelectronics industry.
    • Should we use an aluminum adhesion layer? Less biocompatible metal than Ti, and more likely to degrade in saline.
  • Found that copper adhesion actually went up with water exposure!
  • Polyimide adheres more strongly to glass than epoxy following accelerated aging.

{1287}
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ref: -0 tags: maleimide azobenzine glutamate photoswitch optogenetics date: 06-16-2014 21:19 gmt revision:0 [head]

PMID-16408092 Allosteric control of an ionotropic glutamate receptor with an optical switch

  • 2006
  • Use an azobenzene (benzine linked by two double-bonded nitrogens) as a photo-switchable allosteric activator that reversibly presents glutamate to an ion channel.
  • PIMD:17521567 Remote control of neuronal activity with a light-gated glutamate receptor.
    • The molecule, in use.
  • Likely the molecule is harder to produce than channelrhodopsin or halorhodopsin, hence less used. Still, it's quite a technology.

{1286}
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ref: -0 tags: ovipositor wasp fig needle insertion SEM date: 05-29-2014 19:58 gmt revision:0 [head]

Biomechanics of substrate boring by fig wasps

  • Lakshminath Kundanati and Namrata Gundiah 2014

{1284}
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ref: -0 tags: noise triboelectric implant BMI date: 05-16-2014 17:28 gmt revision:1 [0] [head]

source -- Durand

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ref: -0 tags: optogenetics glutamate azobenzine date: 05-07-2014 19:51 gmt revision:0 [head]

PMID-17521567 Remote control of neuronal activity with a light-gated glutamate receptor.

  • Neuron 2007.
  • azobenzines undergo a cis to trans confirmational change via illumination with one wavelength, and trans to cis via another. (neat!!)
  • This was used to create photo-controlled (on and off) glutamate channels.

{1282}
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ref: -0 tags: polyimide adhesion aluminum integrated circuit date: 05-07-2014 19:29 gmt revision:0 [head]

Polyimide insulators for multilevel interconnections Arthur M. Wilson

  • Old article (1981), but has useful historical information on the development of various PI insulators and their adhesion to aluminum, SiOx, etc.
  • Suggests that a higher-temperature cure (400C) is needed to fully drive water from the PI & cause a glass-transition. Might want to do this for the second PI layer.

{1281}
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ref: -0 tags: microelectrode patents date: 05-02-2014 00:07 gmt revision:1 [0] [head]

Various microelectrode patents:

Microelectronics:

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ref: -0 tags: kevlar polyamide orientation thin-films date: 04-07-2014 19:08 gmt revision:1 [0] [head]

Preparation of uniaxially oriented polyamide films by vacuum deposition polymerization

  • Jiro Sakata, Midori Mochizuki
  • Grew polyamide (PPTA, kevlar) films using VDP (vacuum deposition polymerization).
    • Two precursors were heated in a vacuum to yield a stoichiometric polymer.
  • Polymer chains were oriented with rubbing with different polymers, e.g. cotton (!)

{1279}
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ref: -0 tags: parylene plasma ALD insulation long-term saline PBS testing date: 04-02-2014 21:32 gmt revision:0 [head]

PMID-23024377 Plasma-assisted atomic layer deposition of Al(2)O(3) and parylene C bi-layer encapsulation for chronic implantable electronics.

  • This report presents an encapsulation scheme that combines Al(2)O(3) by atomic layer deposition with parylene C.
  • Al2O3 layer deposited using PAALD process-500 cycles of TMA + O2 gas.
  • Alumina and parylene coating lasted at least 3 times longer than parylene coated samples tested at 80 °C
    • That's it?
  • The consistency of leakage current suggests that no obvious corrosion was occurring to the Al2O3 film. The extremely low leakage current (≤20 pA) was excellent for IDEs after roughly three years of equivalent soaking time at 37 °C.
    • Still, they warn that it may not work as well for in-vivo devices, which are subject to tethering forces and micromotion.

{1278}
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ref: -0 tags: carbon fiber electrode array parylene fire sharpening microthread date: 03-20-2014 19:57 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-23860226 A carbon-fiber electrode array for long-term neural recording.

  • Guitchounts G1, Markowitz JE, Liberti WA, Gardner TJ.
  • We describe an assembly method for a 16-channel electrode array consisting of carbon fibers (<5 µm diameter) individually insulated with Parylene-C and fire-sharpened. The diameter of the array is approximately 26 µm along the full extent of the implant.
  • Fibers from http://www.goodfellowusa.com/
    • young's modulus of 380GPa vs. tungsten 400GPa.
    • Data available from Toho Tenax
  • The absence of any report of single neuron isolation in HVC with a fixed chronic electrode implant underscores the difficulty of recording small cells (8-15um soma) with an implant whose damage length scale is large relative to the target neurons. (!!)

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ref: -0 tags: polyimide adhesion oxygen nitrogen plasma surface energy date: 03-10-2014 22:33 gmt revision:0 [head]

Adhesion Properties of Electroless-Plated Cu Layers on Polyimide Treated by Inductively Coupled Plasmas

  • O2 then N2/H2 ICP treatment of polyimide surfaces dramatically lowers the surface energy (as measured by contact angle), and increases the adhesion of palladium-catalyzed electroless copper.
  • Particularly, C-N bonds are increased as revealed by XPS.
  • No peel-strength measurements given.

{1274}
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ref: -0 tags: flexible neural probe polyimide silicon polyethylene glycol dissolvable jove livermore loren frank date: 03-05-2014 19:18 gmt revision:0 [head]

http://www.jove.com/video/50609/insertion-flexible-neural-probes-using-rigid-stiffeners-attached-with

  • details the flip-chip bonding method (clever!)
  • as well as the silicon stiffener fabrication process.

{1272}
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ref: -0 tags: palladium metal glass tought strong caltech date: 02-25-2014 19:02 gmt revision:1 [0] [head]

A damage-tolerant glass

  • Perhaps useful for the inserter needle?
  • WC-Co Tungesten carbide-cobalt cermet is another alternative.

{1273}
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ref: -0 tags: spectroscopy frequency domain PMT avalanche diode laser Tufts date: 02-25-2014 19:02 gmt revision:0 [head]

Frequency-domain techniques for tissue spectroscopy and imaging

  • 52 pages, book chapter
  • Good detail on bandwidth, tissue absorption, various technologies.

{1269}
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ref: -0 tags: hinton convolutional deep networks image recognition 2012 date: 01-11-2014 20:14 gmt revision:0 [head]

ImageNet Classification with Deep Convolutional Networks

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ref: -0 tags: perl directory descent script remove date: 01-10-2014 06:12 gmt revision:0 [head]

Simple perl scrip for removing duplicate files within sub-directories of a known depth:

#!/usr/bin/perl -w

@files = <*>;
foreach $file (@files) {
	@files2 = <$file/*>;
	foreach $file2 (@files2) {
		print $file2 . "\n";
		`rm -rf $file2/*_1.jpg`; 
		`rm -rf $file2/*_2.jpg`; 
	}
}

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ref: Cheung-2007.03 tags: flexible electrode array Michigan probe histology Vancouver current source density EPFL polyimide date: 12-21-2013 21:07 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-17027251[0] Flexible polyimide microelectrode array for in vivo recordings and current source density analysis.

  • Polyimide -- PI-2611 precusor.
  • 50nm Ti adhesion, 200nm Pt, both sputtered.
  • Electrodes etched via RIE in Cl2.
    • Sputtered and photo-patterned SiO2 etch mask.
  • Used regular solder to connect to a Samtec.
  • 15um total thickness.
  • 25um electrode diameter.
  • They were inserted directly (no carrier nor guide) into the brain; can be re-used.
  • Tested to 8 weeks.
  • No figure comparing silicon and polyimide, though they claim minimal GFAP response to the electrodes.

____References____

[0] Cheung KC, Renaud P, Tanila H, Djupsund K, Flexible polyimide microelectrode array for in vivo recordings and current source density analysis.Biosens Bioelectron 22:8, 1783-90 (2007 Mar 15)

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ref: -0 tags: stretchable nanoparticle conductors gold polyurethane flocculation date: 12-13-2013 02:12 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-23863931 Stretchable nanoparticle conductors with self-organized conductive pathways.

  • 13nm gold nanoparticles, citrate-stabilized colloidal solution
    • Details of fabrication procedure in methods & supp. materials.
  • Films are prepared in water and dried (like paint)
  • LBL = layer by layer. layer of polyurethane + layer of gold nanoparticles.
    • Order of magnitude higher conductivity than the
  • VAF = vacuum assisted floculation.
    • Mix Au-citrate nanoparticles + polyurethane and pass through filter paper.
    • Peel the flocculant from the filter paper & dry.
  • Conductivity of the LBL films ~ 1e4 S/cm -> 1e-6 Ohm*m (pure gold = 2 x 10-8, 50 x better)
  • VAF = 1e3 S/cm -> 1e-5 Ohm*m. Still pretty good.
    • This equates to a resistance of 1k / mm in a 10um^2 cross-sectional area wire (2um x 5 um, e.g.)
  • The material can sustain > 100% strain when thermo-laminated.
    • Laminated: 120C at 20 MPa for 1 hour.
  • See also: Preparation of highly conductive gold patterns on polyimide via shaking-assisted layer-by-layer deposition of gold nanoparticles
    • Patterned via MCP -- microcontact printing(aka rubber-stamping)
    • Bulk conductivity of annealed (150C) films near that of pure gold (?)
    • No mechanical properties, though; unlcear if these films are more flexible / ductile than evaporated film.

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ref: -0 tags: shape memory polymers neural interface thiolene date: 12-06-2013 22:55 gmt revision:0 [head]

PMID-23852172 A comparison of polymer substrates for photolithographic processing of flexible bioelectronics

  • Describe the deployment of shape-memory polymers for a neural interface
    • Thiol-ene/acrrylate network (see figures)
    • Noble metals react strongly to the thiols, yielding good adhesion.
  • Cr/Au thin films.
  • Devices change modulus as they absorb water; clever!
  • Transfer by polymerization patterning of electrodes (rather than direct sputtering).
    • This + thiol adhesion still might not be sufficient to prevent micro-cracks.
  • "Neural interfaces fabricated on thiol-ene/acrylate substrates demonstrate long-term fidelity through both in vitro impedance spectroscopy and the recording of driven local field potentials for 8 weeks in the auditory cortex of laboratory rats. "
  • Impedance decreases from 1M @ 1kHz to ~ 100k over the course of 8 weeks. Is this acceptable? Seems like the insulator is degrading (increased capacitance; they do not show phase of impedance)
  • PBS uptake @ 37C:
    • PI seems to have substantial PBS uptake -- 2%
    • PDMS the lowest -- 0.22%
    • PEN (polyethelene napathalate) -- 0.36%
    • Thiol-ene/acrylate 2.19%
  • Big problem is that during photolithographic processing all the shape-memory polymers go through Tg, and become soft/rubbery, making thin metal film adhesion difficult.
    • Wonder if you could pattern more flexible materials, e.g. carbon nanotubes (?)
  • Good paper, many useful references!

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ref: -0 tags: DBS parkinsons dystonia review neurosurgery date: 10-05-2013 22:33 gmt revision:0 [head]

PMID-17848864 Deep brain stimulation

  • Kern DS, Kumar R. 2007
  • extensive review!

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ref: -0 tags: polyimide platinum electrodes Spain longitudinal intrafasicular adhesion delamination date: 10-05-2013 22:24 gmt revision:4 [3] [2] [1] [0] [head]

PMID-17278585 Assessment of biocompatibility of chronically implanted polyimide and platinum intrafascicular electrodes. 2007

  • Designed platinum/polyimide longitudinal intrafasicular electrodes (LIFEs)
    • 25um PT/Ir, insulated to 60-75um diameter. PT/IR has a young's modulus of 202 Gpa.
      • Plated with platinum black under sonication, as this forms a tougher surface than without sonication.
      • See also: PMID-20485478 Improving impedance of implantable microwire multi-electrode arrays by ultrasonic electroplating of durable platinum black. Desai SA, Rolston JD, Guo L, Potter SM. 2010
    • Polyimide PI2611, 10um thick, 50mm long, 220um wide in the electrode segment.
  • Implanted into rat sciatic nerve for 3 months.
  • These electrodes have been tested in people for two days:
    • Electrical stimulation through the implanted electrodes elicited graded sensations of touch, joint movement, and position, referring to the missing limb. This suggested that peripheral nerve interfaces could be used to provide amputees with prosthetic limbs with sensory feedback and volitional control that is more natural than what is possible with current myoelectric and body-powered prostheses.
  • CMAPs = compound muscle action potentials.
  • CNAPs = compound nerve action potentials.
  • Platinum wire LIFE performed very similarly to the thin-film polyimide LIFE in most all tests, with slightly higher potentials recorded by the larger polyimide probe.
  • 'Higher encapsulation with the polyimide probes! Geometry?
  • However, the polyimide LIFEs induced less functional decline than the wire LIFEs.
  • Other polyimide studies [14] [16] [24] -- one of which they observed a 70% reduction of tensile strength after 11 months of implantation.
    • [14] F. J. Rodríguez, D. Ceballos, M. Schüttler, E. Valderrama, T. Stieglitz, and X. Navarro, “Polyimide cuff electrodes for peripheral nerve stimulation,” J. Neurosci. Meth., vol. 98, pp. 105–118, 2000.
    • [16] N. Lago, D. Ceballos, F. J. Rodríguez, T. Stieglitz, and X. Navarro, “Long term assessment of axonal regeneration through polyimide regenerative electrodes to interface the peripheral nerve,” Biomaterials, vol. 26, pp. 2021–2031, 2005.
    • [24] M. Schuettler, K. P. Koch, and T. Stieglitz, “Investigations on explanted micromachined nerve electrodes,” in Proc. 8th Annu. Int. Conf. Int. Functional Electrical Stimulation Soc., Maroochydore, Australia, 2003, pp. 306–310.
      • The technology of sandwiching a metallization layer between two layers of polyimide seems to be suitable, because no delamination of the polyimide layers was observed even after 11 months. The right choice of metals for building the electrical conductive elements of the microelectrodes is crucial. Ti/Au/Ti/Pt layers tend to flake off from polyimide while delamination of Ti/Pt layers was not observed. However, adhesion of Ti/Pt layers was investigated after 2.5 months of implantation while Ti/Au/Ti/Pt layers were exposed after 11 months to the biological system. In previous research projects, surgeons also reported on delamination of Ti/Au layers from polyimide substrate after three months. Unfortunately, we had no possibility of inspecting these microelectrodes in our laboratory.
      • See also {1250}

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ref: -0 tags: polyimide flexible cable frontiers florida date: 10-04-2013 01:55 gmt revision:0 [head]

PMID-24062716 A highly compliant serpentine shaped polyimide interconnect for front-end strain relief in chronic neural implants.

  • Sankar V, Sanchez JC, McCumiskey E, Brown N, Taylor CR, Ehlert GJ, Sodano HA, Nishida T.
  • 20um polyimide / gold / 20um polyimide.
    • No tie layer; then again, no longevity testing either.
  • Used sacrificial aluminum coating to release polyimide.

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ref: -0 tags: polyimide adhesion silver surface treatment adhesion delamination date: 10-04-2013 01:30 gmt revision:8 [7] [6] [5] [4] [3] [2] [head]

Improved polyimide/metal adhesion by chemical modification approaches

  • Suggest fuming sulfuric acid (H2S04) + Ag2SO4 for 30s as the most effective treatment.
  • 1 minute in 1M KOH also effective.
  • Silver was magnetron-sputtered on; peel test performed with tape.

IEEE-4936772 (pdf) Studies of adhesion of metal films to polyimide

  • Suggest Ar / O2 plasma treatment of surface to increase Cr/Cu adhesion (mechanical effect?)
  • Used two different polyimides: one derived from (BPDA‐PDA) polyamic acid, and pyromellitic dianhydride‐4,4’‐oxydianiline (PMDA‐ODA).

IEEE-670747 (pdf) Adhesion evaluation of adhesiveless metal/polyimide substrate for MCM and high density packaging

  • Adhesion of Cr / polyimide interface is degraded significantly upon exposure to high temperature and humidity environment due to the hydrolysis of polyimide.
  • There is also some worry of Cu diffusion into the polyimide.
  • All used a Cr tie layer, 200A thick (20nm).
  • Deposited photoresist, electroplated copper, then etched to define pattern.
  • Testing performed at 121C 100% RH, +15psi. (tough!)

On polyimide-polyimide interlayer adhesion: Diffusion and self-adhesion of the polyimide PMDA-ODA (1987)

  • Diffusion occurred during the curing process of the second layer and was controlled by the cure schedule.
  • It was found that a large diffusion distance, at least 200 nm, was required to obtain a bond whose strength was equal to that of bulk material.
  • Good protocol:
    • Dry first layer at 80C for 30 minutes.
    • 150C (or lower?) bake of first layer. "as the polyamic acid imidizes (and the solvent is lost) its diffusive mobility decreases rapidly; very little diffusion occurs after the first few minutes of the second bake.
    • Spin coat second layer.
    • 400C second bake.
  • Ductility is increased for polyimide that has experienced a series of increasing cure temperatures.
  • In this context it is worth noting that the contour length of a PMDA-ODA of 30,000 molecular weight is about 130nm, a value very similar to the diffusion distances measured when T1 (first layer bake) was 150C.

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ref: -0 tags: Anna Roe optogenetics artificial dura monkeys intrinisic imaging date: 09-30-2013 19:08 gmt revision:3 [2] [1] [0] [head]

PMID-23761700 Optogenetics through windows on the brain in nonhuman primates

  • technique paper.
  • placed over the visual cortex.
  • Injected virus through the artificial dura -- micropipette, not CVD.
  • Strong expression:
  • See also: PMID-19409264 (Boyden, 2009)

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ref: -0 tags: woodchuck post-translational regulatory element date: 09-30-2013 18:52 gmt revision:2 [1] [0] [head]

PMID-10074136 Woodchuck hepatitis virus posttranscriptional regulatory element enhances expression of transgenes delivered by retroviral vectors 1999

  • "These results demonstrate that the WPRE significantly improves the performance of retroviral vectors and emphasize that posttranscriptional regulation of gene expression should be taken into account in the design of gene delivery systems."
  • Only useful in Cre recombinase sites (? I don't know much about this!)
  • used in e.g {1255}

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ref: -0 tags: buszaki watson oscillations review gamma theta hippocampus cortex date: 09-30-2013 18:32 gmt revision:2 [1] [0] [head]

PMID-23393413 Brain rhythms and neural syntax: implications for efficient coding of cognitive content and neuropsychiatric disease.

  • His frequency band standards:
    • delta: 1.5 - 4Hz
    • theta: 4 - 10Hz
    • beta: 10 - 30 Hz
    • gamma: 30 - 80Hz
    • fast: 80 - 200 Hz
    • ultra fast: 200 - 600 Hz.
  • comodugram: power-power correlelogram
  • Reviews current understanding of important rhythms:
    • How gamma is preserved amongs mammals, owing to the same fundamental mechanisms (membrane time constant, GABA transmission, AMPA receptior latency) all around 25ms; suggests that this is a means of tieing neurons into meaningful groups. or symbols; (solves the binding problem?)
    • Theta rhythm, in comparison, varies between species, inversely based on the size of the hippocampus. Larger hippocampus -> greater axonal delay.
    • These and other the critical step is to break neurons into symbols (as part of a 'language' or sequenced computation), not arbitrarily long trains of spikes which are arbitrarily difficult to parse.
  • Reviews the potential role of oscillations in active sensing, though with a rather conjectorial voice: suggests that sensory systems
  • Suggests that neocortical slow-wave oscillations during sleep are critical for transferring information from the hippocampus to the cortex: the cortex become excitable at particular phases of SWS, which biases the fast ripples from the hippocampus. During wakefulness, the direction is reversed -- the hippocampus 'requests' information from the neocortex by gating gamma with theta rhythms.
  • "Typically, when oscillators of different freqencies are coupled, the network oscillation frequency is determined by the fastest one. (??)
  • I actually find figure 3 to be rather weak -- the couplings are not that obvious, espeically if this is the cherry-picked example.
  • Cross phasing-coupling, or n:m coupling: one observes m events associated with the “driven” cycle of one frequency occurring at n different times or phases in the “stimulus” cycle of the other.
    • The mechanism of cross-frequency coupling may for the backbone of neural syntax, which allows for both segmentation and linking of cell assemblies into assemblies (leters) and sequences (words). Hmm. this seems like a stretch, but I am ever cautious.
  • Brain oscillations for quantifiable phenotypes! e.g. you can mono-zygotic twins apart from di-zygotic twins.

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ref: -0 tags: Disseroth Kreitzer parkinsons optogenetics D1 D2 6OHDA date: 09-30-2013 18:15 gmt revision:0 [head]

PMID-20613723 Regulation of parkinsonian motor behaviors by optogenetic control of basal ganglia circuitry

  • Kravitz AV, Freeze BS, Parker PR, Kay K, Thwin MT, Deisseroth K, Kreitzer AC.
  • Generated mouse lines with channelrhodopsin2, with Cre recombinase under control of regulatory elements for the dopamine D1 (direct) or D2 (indirect) receptor.
  • optogenetic exitation of the indirect pathway elicited a parkinsonian state: increased freezing, bradykinesia and decreased locomotor initiations;
  • Activation of the direct pathway decreased freezing and increased locomotion.
  • Then: 6OHDA depletion of striatal dopamine neurons.
  • Optogenetic activation of direct pathway (D1 Cre/loxp) neurons restored behavior to pre-lesion levels.
    • Hence, this seems like a good target for therapy.

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ref: -0 tags: parylene metal adhesion Stieglitz date: 08-15-2013 17:22 gmt revision:0 [head]

PMID-20119944 Characterization of parylene C as an encapsulation material for implanted neural prostheses.

  • On Si3N4, platinum, and a first film of parylene-C, satisfactory adhesion was achieved with silane A-174, even after steam sterilization. (>1 N/cm)
  • higher adhesion for the parylene that was deposited at lower pressures.
  • but: higher deposition pressures results in lower crystalinity.
  • [33] parylene can be used to build freestanding nanowires.
  • Parylene does not stick to polyimide.
  • Parylene sticks to parylene well if left untreated.
  • Annealing parylene dramatically increased crystalinity / decreases elongation to break.
  • The deposited parylene C layers on untreated and with oxygen plasma-treated samples delaminated immediately after contact with saline. The behavior was also observed at two out of three samples of the A-174 treated wafers, but not in this magnitude.
    • A potential reason for these results could be contamination of the samples during assembly or excessive treatment with the adhesion promoter.

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ref: -0 tags: Kozai carbon nanotube electrode rcording histology date: 08-02-2013 05:42 gmt revision:1 [0] [head]

PMID-23142839 Ultrasmall implantable composite microelectrodes with bioactive surfaces for chronic neural interfaces.

  • Here, we report the development of an integrated composite electrode consisting of a carbon-fibre core, a poly(p-xylylene)-based thin-film coating that acts as a dielectric barrier and that is functionalized to control intrinsic biological processes, and a poly(thiophene)-based recording pad.
  • 7um diameter carbon nanotubes slide easily into cortex & yield good recording.
  • only 0.8um of parlyene-N coating.
    • Does it stick well? Does it crack?
  • Functionalized the parylene with 50nm of bromine / oxygen complex, bromoisobutyrate.
  • PEDOT recording surface drastically lowered impedance.
  • Difficult to assemble these little buggers!

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ref: -0 tags: retinal ganglion cells neural encoding Farrow date: 07-31-2013 16:21 gmt revision:0 [head]

PMID-21273316 Physiological clustering of visual channels in the mouse retina

  • Anatomy predicts that mammalian retinas should have in excess of 12 physiological channels, each encoding a specific aspect of the visual scene.
  • Although several channels have been correlated with morphological cell types, the number of morphological types generally exceeds the known physiological types.
  • Here, we attempted to sort the ganglion cells of the mouse retina purely on a physiological basis.
  • Result: The optimal partition was the 12-cluster solution of the Fuzzy Gustafson-Kessel algorithm.
    • This might be useful elsewhere ...
  • Farrow Lab is responsible for the 11,011 electrode array.

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ref: -0 tags: ACF chip bonding parylene field's metal polyimide date: 07-10-2013 18:34 gmt revision:10 [9] [8] [7] [6] [5] [4] [head]

We're making parylene electrodes for neural recording, and one critical step is connecting them to recording electronics.

Currently Berkeley uses ACF (anisotropic conductive film) for connection, which is widely used for connecting flex tape to LCD panels, or for connecting driver chips to LCD glass. According to the internet, pitches can be as low as 20um, with pad areas as low as 800um^2. source

However, this does not seem to be a very reliable nor compact process with platinum films on parylene, possibly because ACF bonding relies on raised areas between mated conductors (current design has the Pt recessed into the parylene), and on rigid substrates. ACF consists of springy polymer balls coated in Ni and Au and embedded in a thermoset epoxy resin. The ACF film is put under moderate temperature (180C) and pressure (3mpa, 430psi), which causes the epoxy to cure in a state that leaves the gold/nickel/polymer balls to be compressed between the two conductors. Hence, even if the conductors move slightly due to thermal cycling, the small balls maintain good mechanical and electrical contact. The balls are dispersed sufficiently in the epoxy matrix that there is little to no chance of conduction between adjacent pads.

(Or so I have learned from the internet.) Now, as mentioned, this is an imperfect method for joining Pt on parylene films, possibly because the parylene is so flexible, and the platinum foil is very thin (200-300 nm). Indeed, platinum does not bond very strongly to parylene, hence care must be taken to allow sufficient overlap to prevent water ingress. My proposed solution -- to be tested shortly -- is to use a low-melting temperature metal with strong wetting ability -- such as Field's metal (bismuth, tin, indium, melting point 149F, see http://www.gizmology.net/fusiblemetals.htm) to low-temperature solder the platinum to a carrier board (initially) or to a custom amplifier ASIC (later!). Parylene is stable to 200C (392F), so this should be safe. One worry is that the indium/bismuth will wet the parylene or polyimide, too; however I consider this unlikely due to the difficulty in attaching parylene to any metal.

That said, there must be good reason why ACF is so popular, so perhaps a better ultimate solution is to stiffen the parylene (or ultimately polyimide) substrate so that it can support both the temperature/pressure of ACF bonding and the stress of a continued electrical/mechanical bond to polyimide fan-out board or ASIC. It may also be possible to gold or nickel electroplate the connector pads to be slightly raised instead of recessed.


Update: ACF bond to rigid 1/2 oz copper, 4mil trace / space connector (3mil trace/space board):

Note that the copper traces are raised, and the parylene is stretched over the uneven surface (this is much easier to see with the stereo microscope). To the left of the image, the ACF paste has been sqeezed out from between the FR4 and parylene. Also note that the platinum can make potential contact with vias in the PCB.


Update 7/2: Fields metal (mentioned above) does stick to platinum reasonably well, but it also sticks to parylene (somewhat), and glass (exceptionally well!). In fact, I had a difficult time removing traces of field's metal from the Pyrex beakers that I was melting the metal with. These beakers were filled with boiling water, which may have been the problem.

When I added flux (Kester flux-pen 951 No-clean MSDS), the metal became noticeably more shiny, and the contact angle increased on the borosilicate glass (e.g. looked more like mercury); this leads me to believe that it is not the metal itself that attaches to glass, but rather oxides of indium and bismuth. Kester 951 flux consists of:

  • 2-propanol 15% (as a denaturing agent) boiling point 82.6C
  • Ethanol 73% (solvent) boiling point 78.3C
  • Butyl Acetate 7% boiling point 127C, flash point 27C
  • Methanol <3% b.p. 64.7C
  • Carboxylic acids < 3% -- proton donors? formic or oxalic acid?
  • Surfacants < 1% -- ?
Total boiling point is 173F.

After coating the parylene/platinum sample with flux, I raised the field's metal to the flux activation point, which released some smoke and left brown organic residues on the bottom of the glass dish. Then I dipped the parylene probe into the molten metal, causing the flux again to be activated, and partially wetting the platinum contacts. The figure below shows the result:

Note the incomplete wetting, all the white solids left from the process, and how the field's metal caused the platinum to delaminate from the parylene when the cable was (accidentally) flexed. Tests with platinum foil revealed that the metal bond was not actually that strong, significantly weaker than that made with a flux-core SnPb solder. also, I'm not sure of the activation temperature of this flux, and think I may have overheated the parylene.


Update 7/10:

Am considering electrodeless Ni / Pt / Au deposition, which occurs in aqueous solution, hence at much lower temperatures than e-beam evaporation Electrodeless Ni ref. On polyimide substrates, there is extensive literature describing how to activate the surface for plating: Polyimides and Other High Temperature Polymers: Synthesis ..., Volume 4. Parylene would likely need a different possibly more aggressive treatment, as it does not have imide bonds to open.

Furthermore, if the parylene / polyimide surface is *not* activated, the electrodeless plating could be specific to the exposed electrode and contact sites, which could help to solve the connector issue by strengthening & thickening the contact areas. The second fairly obvious solution is to planarize the contact site on the PCB, too, as seen above. ACF bonds can be quite reliable; last night I took apart (and successfully re-assembled) my 32" Samsung LCD monitor, and none of the flex-on-glass or chip-on-flex binds failed (despite my clumsy hands!).

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ref: -0 tags: Utah parylene cracking encapsulation electrode date: 06-28-2013 18:26 gmt revision:4 [3] [2] [1] [0] [head]

Characterization of parylene-C film as an encapsulation material for neural interface devices

  • Hsu, Jui-Meia; Kammer, Saschab; Jung, Erikc; Rieth, Lorend; Normann,A. Richarde; Solzbacher, Florianade (Utah)
  • lists Tg 35-80C for parylene-C;
  • 3um films applied.
  • Parylene samples were subjected to accelerated lifetime testing (85 % relative humidity (RH) and 85 ̊C) for 20 days, and the film did not show appearance changes as observed by optical microscopy. However, X-ray diffractograms show that the film crystallinity increased during this test.
  • 120C 100%RH for 2 hours released parylene from the silicon.
  • Soldering @ 350C backside of Utah array caused parylene to crack.
  • X-ray diffraction shows that heat causes parylene to crystalize:

___Low Dielectric Constant Materials for Ic Applications___ edited by Paul Shin Ho, Jihperng Leu, Wei William Lee

  • Aging and annealing increase crystalinity and thus lower the elongation to break and increase the modulus and mechanical strength of the films.
  • parylene-N is considerably more crystaline (57%), Tg 13C. (low!)
  • Bulk barrier properties are among the best of the organic polymeric coatings.

{1246}
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ref: -0 tags: parylene microchannel micromolding glass transition temperature microfluidics date: 06-28-2013 17:34 gmt revision:3 [2] [1] [0] [head]

Parylene micromolding, a rapid low-cost fabrication method for parylene microchannel

  • doi:10.1016/j.snb.2003.09.038
  • Hong-Seok Noha∗ , Yong Huangb, Peter J. Hesketha Clemson
  • Parylene properties:
    • Glass transition temperature <90C; c.f. {1247}
    • Melting point 290C
    • Oxidation in air at 120C
    • Thermal bonding here at 200C in a vacuum oven @ 24MPa.

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ref: -0 tags: polyimide aging deadhesion humidity water absorption date: 06-28-2013 02:07 gmt revision:1 [0] [head]

Environmental Aging and Deadhesion of Polyimide Dielectric films

  • At 35C, 85% RH (not immersion!) there was little degradation in the polyimide to 2000 hours.
  • Suggest chromium or titanium as an adhesion promoter & to prevent copper from diffusing into the polyimide.
  • Plasma treatment of polyimide is commonly used prior to metal deposition in order to improve adhesion of polyimide to metallization [20].
    • Clearfield, Furman, Callegari 1994 "The Role of Physical and Chemical Structure in the Long-term Durability of Metal/Polyimide Interfaces" International Journal of Microcircuits and electronic Packaging 17(3), pp. 228-35.

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ref: -0 tags: polyimide electrodes ecog japan photosensitive date: 06-28-2013 01:50 gmt revision:0 [head]

PMID-22719725 Photosensitive-polyimide based method for fabricating various neural electrode architectures

  • Yasuhiro X. Kato,1,* Shigeto Furukawa,2 Kazuyuki Samejima,1 Naoyuki Hironaka,2 and Makio Kashino2
  • many typos in this paper (not that I should talk..) Yet still, it's informative.
  • 12um thick photosensitive polyimide + Cr/Au fabrication.
  • Wet etch (photodeveloper).
  • Wet release (ferric chloride) from glass substrate.
  • Soldered a connector to the polyimide w/ stiffener.
  • Note that polyimide tends to shrink (up to 29%) during baking, unlike parylene!
  • Suggest 20-40um diameter neural recording sites; they did not coat.

{1243}
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ref: -0 tags: polyimide platinum nanowire recording electrode plating date: 06-28-2013 00:46 gmt revision:2 [1] [0] [head]

IEEE-5734597 (pdf) A novel platinum nanowire-coated neural electrode and its electrochemical and biological characterization

  • Young-Hyun Jin ; IMTEK, Univ. of Freiburg, Freiburg, Germany ; Daubinger, P. ; Fiebich, B.L. ; Stieglitz, T.
  • 10um thick RIE etched polyimide and platinum electrodes.
  • polyimide was spin coated onto wafers.
  • Used relatively simple wet chemistry to plate platinum onto electrodes:
    • 0.14 M-% chloroplatin acid hexahydrate (H2PtCl6·6H2O, Sigma-Aldrich) and 7.4 M-% formic acid (HCOOH, Sigma-Aldrich) were mixed in de-ionized (DI) water. The fabricated device was floated upside down on the solution.
  • Let this plate for 7 days & effective site was enlarged by 617 times!

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ref: Prasad-2012.1 tags: tungsten microwire electrodes histology insulation failure sanchez microwire tungsten date: 06-27-2013 22:40 gmt revision:12 [11] [10] [9] [8] [7] [6] [head]

PMID-23010756[0] Comprehensive characterization and failure modes of tungsten microwire arrays in chronic neural implants.

  • c.f. [1]
  • microwire implant, durations that ranged from acute to up to 9 months in 25 rats.
  • First 2-3 weeks electrode impedance + recording quality fluctuated the most widely.
  • Electrode recording site deterioration continued for the long-term animals as insulation damage occurred and recording surface became more recessed over time.
  • Activated microglia were found near electrode tracts in all chronic animals.
    • High ferritin expression, intraparenchymal bleeding, microglial degeneration suggesting presence of excessive oxidative stress via Fenton chemistry.
      • Wikipedia: Free iron is toxic to cells as it acts as a catalyst in the formation of free radicals from reactive oxygen species via the Fenton Reaction.[11] Hence vertebrates use an elaborate set of protective mechanisms to bind iron in various tissue compartments.
  • Ferritin expression sometimes associated with blebbing / cytorrhexis. (in figures 7-8)
    • Interestingly, during the first few hours after implantation many microglial cells are undergoing cytoplasmic fragmentation (cytorrhexis) which indicates ongoing degeneration of these cells as their cytoplasm literally breaks apart. Cytorrhexis has been previously observed in the aged human brain where it becomes particular prominent in subjects with Alzheimer’s disease.
  • Could not discriminate abiotic (insulation, recording site size) and biotic (inflammatory response) causes of failure.
    • Microglial response not correlated with prolonged performance.
  • Tungsten TDT microwire arrays. 50um diameter, 10um polyimide insulation.
  • SEM imaging pre and prior implantation.
  • Antibodies marking microglia:
    • Iba1 marks all microglia.
    • ED1 stain against CD68 to identify active macrophages [80], but not necessarily all activated microglia since many activated cells are not engaged in phagocytosis and thus are ED1-negative.
    • Anti-ferritin staining to identify those microglia involved in the sequestration of free iron that may leak as a result of BBB compromize.
      • Issue: ferritin is expressed in all tissues ..
    • OX-6 to identify antigen-presenting MHC-II (immune) cells, e.g. microglia or blood-borne immune cells.
  • Found the immunohistoheamistry not terribly convincing.
    • Above, arrows show withdrawn electrode tips.
  • Working with the FDA to promote good laboratory practice (GLP) and good manufacturing practice (GMP). Can mention the same.
  • No evidence of infection in rats.
    • Not true in monkeys..

____References____

[0] Prasad A, Xue QS, Sankar V, Nishida T, Shaw G, Streit WJ, Sanchez JC, Comprehensive characterization and failure modes of tungsten microwire arrays in chronic neural implants.J Neural Eng 9:5, 056015 (2012 Oct)
[1] Freire MA, Morya E, Faber J, Santos JR, Guimaraes JS, Lemos NA, Sameshima K, Pereira A, Ribeiro S, Nicolelis MA, Comprehensive analysis of tissue preservation and recording quality from chronic multielectrode implants.PLoS One 6:11, e27554 (2011)

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ref: -0 tags: asynchronous design Rajit Manohar Octasic date: 06-12-2013 00:19 gmt revision:5 [4] [3] [2] [1] [0] [head]

At Cornell I took a VLSI design class taught by Rajit Manohar (*), and even then - 2002/2003 - he was very excited about asynchronous circuit design. I was uncertain about the technology at the time, but generally I trusted his instinct. Seems that there is certainly some oil in those hills - Octasic has just released a new basestation IC based on asynchronous processor cores: http://www.octasic.com/en/products/oct2200/oct2224w.php

The associated product-brief/technology whitepaper gives some good motivations for why asynchronous design is superior to classical synchronous design: (I'll quote, since I find this fascinating, hope they don't mind!)

  • Elimination of clock trees - Synchronous high-speed processors require large clock trees to keep sequential blocks synchronized. These clock trees require high-power buffers to drive complex high-capacitance networks that cover most of the chip. Clocks change state twice per cycle, consuming power on both positive and negative edges. These clock trees do not perform any information processing, thus provide no useful computing work, yet they consume a significant portion of the total power. Eliminating the clock trees alone can reduce power consumption by as much as 40% in a high-performance processor.
  • Elimination of pipeline state elements - Modern synchronous high-performance processors rely heavily on pipeline design techniques. Those pipelines require the use of a very large number of inter-stage flip-flops and state elements to support a high clock frequency operation. However, these inter-stage flip-flops and state elements also dont contribute to the actual data processing and computing tasks performed by the processor. In an asynchronous design these storage elements are discarded, saving the silicon space they occupy and the large amount of power they consume.
  • Elimination of lost margin timing - These inter-stage flip-flops require set-up and hold times which force a significant portion of the time between clock edges to be unusable for computation in high-frequency synchronous designs. Moreover given that each sub-micron technology shrink tends to increase path timing uncertainty, this further shortens the active period that can be used to achieve useful work between clock edges. This also means that in a synchronous design, the inter-stage circuit logic needs to be designed to operate increasingly faster than a single clock period to perform the same work. This requires the increased use of larger, higher power buffers in the datapath. In an asynchronous processor design, the logic does not have to deal with such small time steps. They can be built using slower, smaller and lower power circuits, while still delivering the same level of overall performance. Because the gates can be slower, it allows more use of low-leakage high-threshold voltage (HVT) gates, which drastically reduces leakage and further reduces power consumption and die area.
  • Reducing wire interconnect length -The silicon area savings discussed above translate into even more power savings, because wires connecting two elements get shorter as the circuits between these elements shrink. Shorter wires have less capacitance, thus switching them requires less power by using smaller buffers

Cool! I expect to see these techniques in many processors in the future - from embedded, very power sensitive MCUs to GPUs!

(*) Rajit was a cool guy. Not only did he give us a good grade, but he even drove us 'downtown' (in the sense of down the hill, Ithaca doesn't really have a downtown) at one point to pick up some resistors and other electronic parts so we could test out MOSIS-fabricated ASIC.

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ref: -0 tags: parylene silicon neural recording probes date: 06-07-2013 00:15 gmt revision:4 [3] [2] [1] [0] [head]

http://thesis.library.caltech.edu/4671/1/PhDThesisFinalChanglinPang.pdf

  • Notes: Michigan probes suffer from thickness limited to <15um, hence are often not stiff enough to penetrate the pia & arachnoid.
  • Likewise, utach arrays are fabricated through a substrate, so cannot be made longer than 1.5-2mm. Plus, they are connected with 25um gold wires, which is both rigid and requires a fair bit of work. (Perhaps with a wirebond machine?)
  • SiO2 suffers from high internal stress (formed at high temperature) and tends to hydrate over time, both making it a less than ideal insulator for biological applications.
    • Silicon is slowly attacked in saline.
  • Use Cr/Au traces, and Ti/Pt electrode sites on his probes.
    • 2.5um minimum trace width.
  • Importantly, they solve the problem of parylene to silicon interconnect by simply fabricating the wires on parylene -- like ours -- and only use silicon as a structural support.
    • Silicon is roughened via XeF2 for good parylene adhesion.
      • Alas, does not survive a long-term soak -- but maybe this is useful? (page 102)
        • This too can be solved via bringing the parylene in vacuum up to melting temperature to better bond with Si.
  • Metal pads on parylene are destroyed by wedge bonding -- heat and pressure are too high!
  • Their solution is to use conductive epoxy & fan the wires out to omnetics pitch (635um) in what they call parylene-PCB-omnetics connector (PPO).
  • Plated a 5um x 5um electrode with platinum black to reduce the impedance from 1.1M to 9.2k (!!)
    • Problem is that Pt black is fragile, and may be scraped off during insertion -- see figure on page 95.
  • Probe shanks are ~ 170um x 150um, tip spade-type patterned via DRIE.
  • To be able to sustain soaking and lifetime testing, thick parylene layers are needed for the flexible parylene cable. The total parylene thickness of our neural probes is about 13 μm which results in a long etching time. We use photoresist as a mask when etching parylene using RIE O2 plasma etching; the etching rate of parylene and photoresist in RIE is roughly 1:1. Thick photoresist (> 20 μm) with high resolution is needed. AZ 9260 thick-film photoresist is designed for the more-demanding higher-resolution thick-resist requirements. It provides high resolution with superior aspect ratios, as well as wide focus and exposure latitude and good sidewall profiles. A process of two spinning coats using AZ 9260 has been developed to make a high-resolution thick photoresist mask of about 30 μm. Figure 4-11 shows the thick photoresist on the probe tip to guarantee a sharp tip after plasma etching. The photoresist is hard baked in oven at 120 oC for 30 min; the thick photoresist needs to be carefully handled during baking to avoid thermal cracking.
  • Otline electrolysis-based actuators ... interesting but hopefully not needed.

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ref: -0 tags: plasma etch removal parylene DRIE date: 05-28-2013 18:47 gmt revision:2 [1] [0] [head]

Plasma removal of Parylene C

  • Ellis Meng, Po-Ying Li and Yu-Chong Tai USC / Caltech
  • Technics O2 plasma etch works, as do DRIE / RIE etch; all offer varying degrees of anisotropy, with the more intricate processes offering straighter sidewalls.
  • Suggested parameters for O2 etch is 200sccm / 200W.
  • Etch will be somewhat isotropic -- top of photoresist will be etched away, leading to ~15deg sloped sidewalls.
    • Hence, small parylene features will be narrowed by the 02 plasma.

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ref: car-0 tags: saab modifications convertible 900 SE date: 04-29-2013 18:09 gmt revision:12 [11] [10] [9] [8] [7] [6] [head]

So, a year and a half ago I bought a green 1995 900 SE convertible for $600. At that time, it didn't move or go in reverse. Since then, I've been fixing up random things here an there (or just straight modifying / breaking the car by other standards) and recently realized that I had better start keeping track of everything that's been done, in case my memory lapses or i need to know where some random part came from. I doubt this will be useful to anyone else - next time, pictures!

Things that I've done to the green convertible, in approximate chronological order:

  1. replaced the clutch cable. previous owner says that the clutch was relatively new; verified when i swapped the transmission.
  2. replaced the turbo transmission with one from a 900 S n/a; new transmission has slightly shorter final drive ratio, which is fun. Both transmissions have approximately the same number of miles on them (again, the original tranny had no reverse).
    1. The subframe brace bolts were seized on this car - it took several weeks off and on + heat + rust solvent to remove both large 18mm bolts. I recommend replacing them with new ones if possible (these look fine, they are very heavy bolts).
    2. In the process of doing this, I stripped one captive nut used for the transmission mount, and had to drill it out & replace it with a 3/8" grade 8 bolt & double nut affair from home cheapo. Be careful when threading these bolts in, or you'll have to do the same!
  3. replaced the rubber boots on the control-arm ball joints, and in turn repacked the ball joints with grease. This takes a lot of patience.
  4. installed a new gas filler hose from the plastic filler line to the gas tank. Previous one was held on with zip-ties. (yes, zip-ties: after i filled the damn thing up, i noticed that it was leaking excessively, and had to drive it around until the gas was burned through & unlikely to drip all over the ground once the car was parked.)
  5. removed turbo silencer prior intercooler.
  6. installed a new passenger side headlamp assembly.
  7. replaced the thermostat.
  8. replaced and gapped all 4 spark plugs.
  9. reflashed the ECU to stage 2.5 or so - 1.4 bar peak boost @ 3k rpm, 1.2 bar above 4k rpm, no boost limit in 2nd gear. This was done via Trionic5 suite, available from http://ecuproject.com/
  10. replaced both front struts & shocks with parts from a junkyard 1997 900 SE; previous ones had a loose / faulty wheel bearing. Very worthy upgrade.
  11. replaced all brake pads + front brake rotors to fit the struts/shocks/bearing hubs from the 97 900 SE. (the hubs are incompatible with 1995 disc rotors - different internal flange diameter.)
  12. replaced both front brake calipers. The previous 1995-version calipers did not mate well with '97 struts and '97 discs. Initially bought used calipers off of ebay, but the damn bleeder valve was sheared off at the nut, so I took the pads off them and installed remaned ones. Brake feel is much, much better now.
  13. added internal bracing / roll cage, though without the top hoop. removed most of the upholstery & seats in the back to fit this.
  14. oil and filter changed at 161k.
  15. adjusted some of the window seals - but they still need to be replaced eventually.
  16. removed condenser and AC compressor.
  17. replaced / changed the serpentine belt to a 71" / 1805mm 6-tooth duralast belt - aka AC delete belt ref. Water pump is only 25% engaged with the belt now, but seems to work just fine (and the internet verifies this.)
  18. repainted some rust spots on the trunk lid.
  19. installed plenty of grease on the upholstery -- oops :P
  20. Got two used tires from America's discount tires; rear tires still shady. Will get around to replacing them; have already gotten around to destroying the front ones with second-gear burnouts to 60 :)
  21. Resurfaced flywheel, replaced clutch disc with one from a Jeep Wagoneer (though not the pressure plate -- it looked fine, no signs of cracking).
  22. Replaced drivers side main crankcase seal.
  23. Replaced drivers side transaxle output bushing + drivers and passengers transaxle output seals
  24. Removed oil pan, cleaned pickup, and re-did oil pan seal.
  25. Welded a new stud on the turbo, applied with anti-seize this time! always use anti-seize on exhaust parts, they get hot!
  26. Removed head, had it ground to fix a minor valve leak and milled flat (increasing the compression ratio a bit). Cleaned the block top surface, intake manifold, fuel injectors, piston heads, and cylinders as best I could. Removed & replaced the broken stud underneath the power steering pump. In the course of having the head out, replaced the relevant seals:
    1. Valve stem seals
    2. Head gasket
    3. Intake gasket
    4. Exhaust gasket
  27. Replaced upper and lower radiator hoses.
  28. As of May 1 2012, I no longer own the car -- I'm off to California, and can't take it with me. May the new owner enjoy it as much as I have!

Things that need to be done to the 'vert:

  1. There is still a click in the rear drivers-side brake, should inspect it; likely brake pads.
  2. New rear tires (!!).
  3. hood gas springs are shot. Meh.

Now, wonders of wonders, I have another of these cars - though a sedan, not a convertible. It cost much more (about 8x as much), and is hence in much better shape. That said, I've had to do the following:

  1. Replaced the rear drivers side brake caliper. In the rain; should have waited for a sunny day, as this took longer than expected. (Everything does.)
  2. New front disc rotors & pads Dec 2008. As of July 2010, they should be replaced soon.
  3. Replaced the clutch + throwout bearing. The latter was making terrible noises back when I drove to Atlanta fall 2008; I nearly didn't make it back.
  4. Removed a "Saab saver" steering rack brace installed by a previous owner. To install this brace, you need to drill through the wheel well, which allows (possibly salty) water to touch the bare metal. As a result of this + stress upon metal that was not engineered to bear it, the wheel well cracked almost to the point where the shock mount was about to go through the hood! I'm glad I caught this while the car was parked, and not while i was going 70!
  5. welded the wheel well back together with 2x1/4" steel strap. I tried to weld to the major braces of the unibody, and later covered everything with plenty of paint and spray-on rubber soundproofing compound. Still, I worry about the opposite side of the metal, where the heat from the welding undoubtably removed rust-preventing paint. Seems reliable so far.
  6. replaced drivers side inner CV joint boot & of course repacked the CV joint grease. You need to take the CV joint completely apart to fit the thing - it won't stretch!
  7. Built a tool for removing the differential output bushing from the transmission. As the output of the differential is only a bushing, and it's put under a lot of stress during hard acceleration (especially peel outs - one wheel spinning much faster than the other = lots of strain on diff), the bushing wears out quickly. It is a pressure fit sleeve, so I reasoned that it could be removed by pressure - not quite. It must be cut out, very tediously, using a single-ended hacksaw. To keep metal debris out of the diff housing, insert a rag into where the CV axle was, and flush the tranny throughly after installing a new bushing.
    1. This is all rather difficult, so don't peel out!
    2. The passengers side half-axle is supported by a bearing by the alternator, so it does not have the same levels of stress & does not wear as quickly.
  8. Four new tires. $560 - beh.
  9. Replaced front brake discs Nov 2010
  10. New front strut inserts + reground front brakes May 2012 -- in Albuquerque.
  11. Flushed transmission oil in the desert outside of Lake Powell; the heat of Phoenix did it in & shifting was starting to be very sticky. Also adjusted the clutch cable, which later snapped while driving in SF. (Fortunately, was able to first gear it to a parking garage, where I fixed it on the spot).
  12. Fan control relay went out in the desert of Utah; ended up shorting it closed with a bit of wire. Said wire must be removed after turning off the car, otherwise the fan will run indefinitely!
  13. Sold car February 2013. May the next owner enjoy her well!

And now the blue 1998 saab 900, sold to Adam:

  1. Replaced front oxygen sensor
  2. Replaced rear transmission mount (had to take off the subframe for this, yuck)
  3. Fixed front passengers side window regulator (ish).
  4. Adjusted clutch master cylinder. The linkage between the pedal and the master cylinder was plastic and badly worn, which was causing the clutch to never fully disengage, in turn gradually leading to third gear synchro wearing out. Adjusted the stop on the pedal to compensate for this; it should ultimately be replaced, though works fine now.
  5. Replaced front drivers side headlight.

Next, the saab 9000 aero:

  1. Swapped wastegate / APC control valve with one from my 900 to remedy overboost issues.
  2. Replaced alternator brushes. Thing was a bear to remove -- had to jack up the engine a bit to get it out!
  3. Re-soldered alternater to battery charging and starting wire
  4. Re-soldered engine-to-chassis grounding wire; transmission to battery wire seemed fine.
  5. Replaced tubing from blow-off valve, PCV, and fuel pressure regulator to intake manifold with aftermarket silicone tubing.
  6. Installed new radio.
  7. Replaced headlight relay.
  8. Replaced turn signal relay.
  9. Replaced thermostat.
  10. Replaced rear lower panhard rod bushing; was falling out and rubbing against the rear axle.
    1. All of the other rear-end suspension bushings looked fine!
  11. Gapped all 4 spark plugs.
  12. New tires @ 120k miles; will need to rotate them.
  13. Cut wire from glass break sensor to security / immobilizer module, as passing buses were setting off the car alarm.
  14. Bought new IAC valve off ebay, put it in (difficult compared to a NG900!), but it idled too high (perhaps I needed to reset the ECU?). Therefore I took the new one out, cleaned and lubricated the old one, and re-installed it. The car still idles high for ~10 seconds when put in neutral, but it comes down, and I suppose I'll live with that for now.
  15. Blocked off the evap & PCV & instrument boost gauge intake manifold barbs in the process of debugging the high idle (figured that there were vacuum leaks).
  16. Replaced central lock relay with a used one from ePartsLand.
  17. Installed new drivers-side wheel bearing. Note you need to take the axle out to get access to the hex-head bolts which hold the hub in. Thankfully, it's not hard once this is done.
  18. New front/rear brakes/rotors.
    1. Front brakes were easy; rear brakes have a hidden retraction allen key.
      1. Follow the directions here. To fit a new rotor and pads, the whole brake caliper needs to be taken apart!
  19. Removed A/C and installed a short belt 2325 mm length.
    1. Note: tensioner pully is threaded backwards to prevent pulley rotation from loosening it.
    2. Note: to disengage the tensioner, you don't need a special tool - just put a breaker bar on a 19mm socket & use that as a lever.
  20. Rear shocks were replaced with Bilstein HD types from thesaabsite.com
  21. Installed new heater core, and all but one of the hoses leading to it.
  22. New fuel filter 121k
  23. Headgasket job April 21-25:
    1. New headgasket + new headbolts. One of them did not torque up to the right 'feel' following the saab-specificed procedure (33ft-lbs, 44ft-lbs, 90deg torque-to-yield. I'm going to replace that one with a M12 12.9 grade bolt from Mcmaster; have ordered 110, 120, and 130mm length & will see which fits best. Original stretch bolts are grade 10.9.
    2. New radiator
    3. New idler pulley
    4. New head gasket + head bolts; only cleaned the block and head, did not have them ground. Seems OK so far!
    5. Flushed oil, though it still took a few hours at temperature to boil off the remaining antifreeze that had leaked into the engine oil.
    6. Kept the timing chain + guides, though it's stretched near the limit; will have to replace next time I have the thing disassembled.
    7. New exhaust manifold. Pain to install, as I didn't remove the turbo when removing the head. Still quite possible.
    8. New urethane engine torque mount. Just cut out the old rubber inserts with a hacksaw -- not too hard. Be careful which way you put in the new blue inserts -- they are asymmetrical.
    9. One new hood gas strut = enough.
    10. New plugs. Old ones were filthy.
  24. Todo
    1. Windshield & Por-15 the frame around it; I bet the previous installer scratched the paint.
    2. Camber bolts to help the tires last longer.

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ref: -0 tags: silicon electrode histology Michigan tip shape shear force date: 04-24-2013 20:02 gmt revision:3 [2] [1] [0] [head]

PMID-1601445 Factors influencing the biocompatibility of insertable silicon microshafts in cerebral cortex.

  • Relatively early assessment of tissue reaction to silicon electrodes.
  • Noted 'severe' reaction at electrode tip; recommend recording along the shaft, Michigan style.
  • Noted microhematoma formation.
  • Recommend fast insertion.
  • Bending of the shafts (e.g. they exert lateral force) causes lateral tissue damage.
    • Problem with fast insertion is that it may cause the needle to bend a bit -- resulting in lateral 'kill zone'.
    • Ultimate speed must be a compromise.
  • Advocate shearing blade tip or chisel point to sever microtubules, rather than a conical tip pushing them to a annular ring that can grab to the sides of the needle.
  • Good paper, reviews the relevant cellular anatomy...

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ref: Schmidt-1978.09 tags: Schmidt BMI original operant conditioning cortex HOT pyramidal information antidromic date: 04-22-2013 18:21 gmt revision:10 [9] [8] [7] [6] [5] [4] [head]

PMID-101388[0] Fine control of operantly conditioned firing patterns of cortical neurons.

  • hand-arm area of M1, 11 or 12 chronic recording electrodes, 3 monkeys.
    • but, they only used one unit at a time in the conditioning task (i think)
  • conditioning in 77% of single units and 65% of combined units (multiunits?).
  • trained to move a handle to a position indicated by 8 annular cursor lights.
    • cursor was updated at 50hz -- this was just a series of lights! talk about simple feedback...
    • Investigated different smoothing: too fast, FR does not stay in target; too slow, cursor acquires target too slowly.
    • My gamma function is very similar to their lowpass filter used for smoothing the firing rates.
    • 4 or 8 target random tracking task
    • time out of 8 seconds
    • run of 40 trials
      • the conditioning reached a significant level of performance after 2.2 runs of 40 trials (in well-trained monkeys); typically, they did 18 runs/day.
  • recordings:
    • scalar mapping of unit firing rate to cursor position.
    • filtered 600-6kHz
    • each accepted spike triggered a generator that produced a pulse of of constant amplitude and width -> this was fed into a lowpass filter (1.5 to 2.5 & 3.5Hz cutoff), and a gain stage, then a ADC, then (presumably) the PDP.
      • can determine if these units were in the pyramidal tract by measuring antidromic delay (stimulate muscles??)
    • recorded one neuron for 108 days!!
      • neuronal activity is still being recorded from one monkey 24 months after chronic implantation of the microelectrodes.
    • average period in which conditioning was attempted was 3.12 days.
  • successful conditioning was always associated with specific repeatable limb movements
    • "However, what appears to be conditioned in these experiments is a movement, and the neuron under study is correlated with that movement." YES.
    • the monkeys clearly learned to make (increasingly refined) movement to modulate the firing activity of the recorded units.
    • the monkey learned to turn off certain units with specific limb positions; the monkey used exaggerated movements for these purposes.
      • e.g. finger and shoulder movements, isometric contraction in one case.
  • Trained some monkeys or > 15 months; animals got better at the task over time.
  • PDP-12 computer!
  • Information measure: 0 bits for missed targets, 2 for a 4 target task, 3 for 8 target task; information rate = total number of bits / time to acquire targets.
    • 3.85 bits/sec peak with 4 targets, 500ms hold time
    • with this, monkeys were able to exert fine control of firing rate.
    • damn! compare to Paninski! [1]
  • 4.29 bits/sec when the same task was performed with a manipulandum & wrist movement
  • they were able to condition 77% of individual neurons and 65% of combined units.
  • Implanted a pyramidal tract electrode in one monkey; both cells recorded at that time were pyramidal tract neurons, antidromic latencies of 1.2 - 1.3ms.
    • failures had no relation to over movements of the monkey.
  • Fetz and Baker [2,3,4,5] found that 65% of precentral neurons could be conditioned for increased or decreased firing rates.
    • and it only took 6.5 minutes, on average, for the units to change firing rates!
  • Summarized in [1].

____References____

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ref: -0 tags: electrode carbon fiber MEA date: 04-22-2013 18:19 gmt revision:2 [1] [0] [head]

PMID-21228307 Ultrasmall and customizable multichannel electrodes for extracellular recordings

  • 7um carbon fiber electrodes.
  • It has been estimated that insertion of a 50 um wire in the adult rat hippocampus CA1 area could damage 90% of the neurons that would otherwise be recordable by the electrode (Claverol-Tinture and Nadasdy 2004)
  • Highlight the tetrode effect: it's like beam forming.
  • Carbon fibers from Goodfellow Cambridge.
  • Insulated with a pulled micropipette.
  • Added insulation with cathodic electrodeposition paint (Claerclad HSR)
  • focused ion beam milling (FIB) (Qiao et al 2005) -- working resolution below 10nm.
  • The carbon fibers were fond to be stiff enough to penetrate the fly 'dura'.

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ref: -0 tags: histology immune response otto indiana electrodes gfap inflamation transparent clearing vimentin date: 04-19-2013 23:59 gmt revision:4 [3] [2] [1] [0] [head]

PMID-23428842 Chronic intracortical microelectrode arrays induce non-uniform, depth-related tissue responses.

  • Woolley AJ, Desai HA, Otto KJ.
  • One timepoint, 4 weeks.
  • Laser confocal microscopy
    • after tissue clearing (optical index of refraction matching) in a 60% sucrose solution.
  • Single-shank iridium contact silicon substrate MEA.
    • Device cut level with surface of brain after insertion.
  • Intact MEAs via device-capture histology, DHhist (Woolley et al 2011)
    • 350-450um tissue explanted with device.
    • They promote their technique.
  • Tissue surrounding microdevices exhibited two major depth-related phenomena:
    • a non-uniform microglial coating along the device length and
    • a dense mass of cells surrounding the implant in cerebral cortical layers I and II.
      • The dense mass of cells contained vimentin, a protein not typically expressed highly in CNS cells, evidence that non-CNS cells likely descended down the face of the penetrating devices from the pial surface.
        • But no Iba1 (activated microglia) per se in the tissue mass.
    • Hoe342 -- cell marker.
    • This mass was apparently consistent across animals!
    • Cells in the mass were VIM positive -- fibroblasts -- meninges?
  • low GFAP = not an astrocytic scar.
  • This study provides further evidence that a progressive invasion of non-CNS cells contributes substantially to the chronic phase of the tissue response around intracortical MEAs.
    • Again, might be from BBB distruption {1237}


This result is supported by previous papers:
  • {1193} -- microglia response not correlated to electrode failure, but correlated to ferritin immunoresponse
  • {781} -- also note that menigeal fibroblasts migrate down electrode tracts.
  • {1028} -- measured vimentin, GFAP, and ED1 (not Iba1). Found Vim+ and GFAP+, suggesting reactive astrocytes and not meningeal cells. ED1 aka CD68 is specific to macrophages and not microglia, so these may be blood-derived cells.
  • {1200} -- chronic contact with the meninges v.s intraparenchymal correlated with Vim+ encapsulation.
  • {1210} -- old paper showing the same result near surface of implant.
  • {1196} -- more against GFAP & pro BBB disruption
  • {1204} -- GFAP uncorrelated (!) with NeuN intensity
  • {307} -- all initial tests of utah arrays showed fibrous encapsulation; one array was completely explanted. This is why now they put gore-tex over the implant -- to prevent fibroblast migration (i guess).

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ref: -0 tags: winslow Tresco 2010 BBB histology immune response microelectrodes date: 04-19-2013 23:25 gmt revision:0 [head]

PMID-19963267 Quantitative analysis of the tissue response to chronically implanted microwire electrodes in rat cortex.

  • Winslow BD, Tresco PA.
  • The spatial distribution of biomarkers associated with the foreign body response to insulated microwires placed in rat cerebral cortex was analyzed 2, 4, and 12 weeks after implantation using quantitative methods.
  • We found no evidence that reactive gliosis increases over time or that neuronal loss is progressive, we did find evidence of persistent inflammation and enhanced BBB permeability at the electrode brain tissue interface that extended over the 3 month indwelling period and that exhibited more animal to animal variability at 3 months than at 2 and 4 weeks.

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ref: -0 tags: journal review neuro date: 04-19-2013 22:58 gmt revision:1 [0] [head]

PLoS One:

PMID-23251670 Ultra-Bright and -Stable Red and Near-Infrared Squaraine Fluorophores for In Vivo Two-Photon Imaging

  • Podgorski K, Terpetschnig E, Klochko OP, Obukhova OM, Haas K.
  • between 750 and 950 nm, where absorption and scattering by tissues is minimized
  • Near-infrared (NIR) probes are ideal for biological imaging because few endogenous molecules in organisms absorb or emit in the NIR region: there is little background autofluorescence to contend with.
  • Squaraine-based fluorescent sensors have been developed for a variety of analytes including Ca2+ [20], pH [21], protein and DNA, and squaraine-based labels exhibit an increase in fluorescence intensity and lifetime upon binding to biomolecules [22], [23]. The photostability of squaraine dyes is comparable to those of conventional cyanine dyes [23], but can be substantially increased by the synthesis of a squaraine-rotaxane [24], an interlocked structure wherein a macrocycle encases the electrophilic squarylium core, preventing its exposure to nucleophilic attack in solution (Fig. 1a).
  • See also (this seems a growing trend):
    • PMID-23292608 Choi, H.S. et al. Targeted zwitterionic near-infrared fluorophores for improved optical imaging. Nat. Biotechnol. 31, 148–153 (2013).
      • focus on low background emission for maximizing SNR & image-guided surgery on tumors.
    • Lukinavičius, G. et al. A near-infrared fluorophore for live-cell super-resolution microscopy of cellular proteins. Nat. Chem. 5, 132–139 (2013).

PMID-22056675 A gene-fusion strategy for stoichiometric and co-localized expression of light-gated membrane proteins

  • Kleinlogel S, Terpitz U, Legrum B, Gökbuget D, Boyden ES, Bamann C, Wood PG, Bamberg E.
  • Push-pull (excitation and inhibition) or complementary (white light) optogenetics.
  • Fused with a gastric chloride pump for good membrane localization.

PMID-22056675 Substantial Generalization of Sensorimotor Learning from Bilateral to Unilateral Movement Conditions

  • Kleinlogel S, Terpitz U, Legrum B, Gökbuget D, Boyden ES, Bamann C, Wood PG, Bamberg E.
  • These findings collectively suggest a substantial overlap between the neural processes underlying bilateral and unilateral movements, supporting the idea that bilateral training, often employed in stroke rehabilitation, is a valid method for improving unilateral performance.

PMID-23408972 Credit Assignment during Movement Reinforcement Learning

  • Chadderdon GL, Neymotin SA, Kerr CC, Lytton WW. -- SUNY Downstate
  • A Bayesian credit-assignment model with built-in forgetting accurately predicts their [humans] trial-by-trial learning.

PMID-23382796 Visuomotor Learning Enhanced by Augmenting Instantaneous Trajectory Error Feedback during Reaching

  • Patton JL, Wei YJ, Bajaj P, Scheidt RA.
  • Learning in the gain 2 and offset groups was nearly twice as fast as controls. not surprising.

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0054771 Flexible Switching of Feedback Control Mechanisms Allows for Learning of Different Task Dynamics

  • unimanual / bimanual tasks.

PMID-23365648 Recognizing Sights, Smells, and Sounds with Gnostic Fields

  • Christopher Kanan UCSD
  • Jerzy Konorski proposed a theoretical model in his final monograph in which competing sets of “gnostic” neurons sitting atop sensory processing hierarchies enabled stimuli to be robustly categorized, despite variations in their presentation.
    • Gnostic: of or relating to knowledge.
    • Supervised learning.
    • "The algorithm can be implemented in a few hours".
  • Tested by classifying contemporary artists from emulated auditory nerve responses. 78% accuracy.
  • Tested for image recognition w/ standardized datasets.
  • Method:
    • Feature-extraction.
    • PCA based whitening.
    • Coarse template matching within the gnostic units via dot product.
      • Feature vector is learned via unsupervised clustering of the whitened training features for each channel and category.
      • Numbre of gnostic units per category set by fn of number of festure vectors and their dimensionality.
    • Take the unit with the largest activity (inhibitive competition).
      • This is a highly nonlinear function
        • which normalizes based on population variability (contraharmonic mean -- weights the inverse of the SNR, effectively).
    • Sum over time.
    • Decode using a linear classifier over the gnostic units.
      • Trained using Balanced Winnow algorithm. (multiplicative and not additive weight updates, allegedly neurally inspired)

PMID-23300606 Decoding Hindlimb Movement for a Brain Machine Interface after a Complete Spinal Transection

  • Manohar A, Flint RD, Knudsen E, Moxon KA.
  • SC transection resulted in a 40% decrease in M1 information content & a persistent reduction in neuronal firing rates.
  • Very similar to Niolelis & Chapin 1999. Meh.
  • See Wyler 1980 {909}

Journal of Neural Engineering:

PMID-23449002 Model-based rational feedback controller design for closed-loop deep brain stimulation of Parkinson's disease.

  • Goal: rational design of stimulation pattern based on control theory.
  • Needed a model of PD, of course -- opted for a thalamic relay controlled by GPi inhibition.
  • Full PID controller

PMID-23428966 Improving brain-machine interface performance by decoding intended future movements.

  • Goal: improve BMI performance by minimizing the deleterious effects of delay in the BMI control loop.
  • We mitigate the effects of delay by decoding the subject's intended movements a short time lead in the future.

PMID-23428937 An implantable wireless neural interface for recording cortical circuit dynamics in moving primates.

  • Borton DA, Yin M, Aceros J, Nurmikko A. Brown.
  • 24Mbps, attached to Utah probe, discussed this with Schwarz.
  • Inductive recharging of li-ion battery.
  • Pigs, etc.

PMID-23428877 Local-learning-based neuron selection for grasping gesture prediction in motor brain machine interfaces.

  • Nonlinear neural activities are decomposed into a set of linear ones in a weighted feature space.
  • Used a margin to segregate different gestures and L1 normalization to remove irrelevant neurons.

PMID-22954906 Sparse decoding of multiple spike trains for brain-machine interfaces.

  • Tankus A, Fried I, Shoham S.
  • Similar idea as above --
  • This method is based on sparse decomposition of the high-dimensional neuronal feature space, projecting it onto a low-dimensional space of codes serving as unique class labels.
  • Tested against a range of existing methods using simulations and recordings of the activity of 1592 neurons in 23 neurosurgical patients who performed motor or speech tasks.

PMID-23010756 Comprehensive characterization and failure modes of tungsten microwire arrays in chronic neural implants.

  • Prasad A, Xue QS, Sankar V, Nishida T, Shaw G, Streit WJ, Sanchez JC.
  • {1193}

PMID-23283391 Performance of conducting polymer electrodes for stimulating neuroprosthetics.

  • Green RA, Matteucci PB, Hassarati RT, Giraud B, Dodds CW, Chen S, Byrnes-Preston PJ, Suaning GJ, Poole-Warren LA, Lovell NH.
  • PEDOT is a fine electrode substrate. Surprising?
  • Can deliver ~ 20x the charge of Pt.

PMID-23160018 Properties and application of a multichannel integrated circuit for low-artifact, patterned electrical stimulation of neural tissue.

  • Hottowy P, Skoczeń A, Gunning DE, Kachiguine S, Mathieson K, Sher A, Wiącek P, Litke AM, Dąbrowski W.
  • Made a 64-channel 'Stimchip'
  • Each channel has a DAC-driven configurable voltage or current source.
    • Has additional artifact-minimization circuitry.
  • Designed for MEAs :-/


Nature Methods:

PMID-23524393 Whole-brain functional imaging at cellular resolution using light-sheet microscopy

  • Ahrens MB, Keller PJ.
  • Here we use light-sheet microscopy to record activity, reported through the genetically encoded calcium indicator GCaMP5G, from the entire volume of the brain of the larval zebrafish in vivo at 0.8 Hz, capturing more than 80% of all neurons at single-cell resolution.
  • 5um slices, 4um thick light sheet.
  • We determined an average signal-to-noise ratio of 180 ± 11 (mean ± s.e.m., n = 31; not considering the signal-to-noise ratio of the calcium indicator itself, see Online Methods) for neurons in different regions of the light sheet–based whole-brain recording. Owing to this high ratio and the short volumetric imaging interval, which was comparable to the time course of GCaMP5G at room temperature, the occurrence of action potentials within the recording interval was detectable in most cases.
  • We used the albino (slc45a2) mutant
    • The mouse brain is significantly bigger, is largely impenetrable to visible light and is surrounded by a skull. Realistically, we may not see methods that enable whole brain activity mapping in mammals at the cellular level for quite a while.
  • Moved the laser light beam in 2 dimensions & the objective in one; laser was scanned via piezoelectric mirrors, and the objective was also peizo-electric control.
    • Used segmentation to tease apart co-active ensembles.
    • Understanding of actual function not too deep, but then again neither was my reading of the paper.
    • Prominent feature is the autonomous hindbrain oscillator.

PMID-23142873 Two-photon optogenetics of dendritic spines and neural circuits

  • In neocortical slices.
  • C1V1 -- combination of ChR1 and VChR1. Slower kinetics more suitable for galvanometer based scanning.
  • AAV virus injected P21 mice, 400um from pial surface of somatosensory cortex.
  • measured currents via patch-clamp.
  • Also tested two-photon spatial light modulator (SLM)-based microscopy, a holographic method that enables optical targeting of groups of neurons or spines located in arbitrary three-dimensional (3D) positions
    • goal: several neurons can be selectively or simultaneously activated in three dimensions—an approach that could enable the optical dissection of the function of microcircuits with single-cell precision.

Nanowires, useful for Flip's idea.

  • These from [editorial http://www.nature.com/nmeth/journal/v9/n4/full/nmeth.1961.html]
  • PMID-22231664 Vertical nanowire electrode arrays as a scalable platform for intracellular interfacing to neuronal circuits
    • Robinson JT, Jorgolli M, Shalek AK, Yoon MH, Gertner RS, Park H. Harvard.
    • looks like it's limited to slices & 100's of neurons atm.
    • Compared to patch-pipe, of course.
    • Lithographic fabrication; pillars were thinned via thermal oxidation and wet chemical etching. Sounds very tricky.
    • 3um microwire length.
    • HEK293 and rat cortical neurons.
  • PMID-22179566 Intracellular recordings of action potentials by an extracellular nanoscale field-effect transistor
  • PMID-22327876 Intracellular recording of action potentials by nanopillar electroporation


Of personal interest:

Richardson-Lucy (RL) deconvolution for sub-diffraction limit imaging.

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0056624 Collaborative Filtering for Brain-Computer Interaction Using Transfer Learning

  • Taylor the language of human-computer interaction to the users, based on k-NN in previous data.

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0055518 Brain Training Game Boosts Executive Functions, Working Memory and Processing

  • 'Brain Age' is effective in a double-blind study.

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0061390 Cognitive Training Improves Sleep Quality and Cognitive Function among Older Adults with Insomnia

  • Debatable causality.

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0054402 Perceived Multi-Tasking Ability, Impulsivity, and Sensation Seeking

  • The findings indicate that the persons who are most capable of multi-tasking effectively are not the persons who are most likely to engage in multiple tasks simultaneously. To the contrary, multi-tasking activity as measured by the Media Multitasking Inventory and self-reported cell phone usage while driving were negatively correlated with actual multi-tasking ability
  • Finally, the findings suggest that people often engage in multi-tasking because they are less able to block out distractions and focus on a singular task. Participants with less executive control - low scorers on the Operation Span task and persons high in impulsivity - tended to report higher levels of multi-tasking activity.

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0052500 Learning and Long-Term Retention of Large-Scale Artificial Languages

  • We report data from a large-scale learning experiment that demonstrates that adults can learn words from unsegmented input in much larger languages than previously documented and that they retain the words they learn for years. These results suggest that statistical word segmentation could be scalable to the challenges of lexical acquisition in natural language learning.
  • A unique artificial language was generated for each participant. Each language had 1000 word types and 60,000 word tokens (for 10 hours of speech). Frequencies of words were distributed via a Zipfian frequency distribution: , where is the frequency of word and is its rank, such that there were a few highly frequent words and many more with lower frequencies (max = 8000, min = 10 tokens) [30].

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0052042 Non-Hebbian Learning Implementation in Light-Controlled Resistive Memory Devices

  • Light and voltage controlled memsistors. Interesting.

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0058284 Attractor Metabolic Networks

  • We have found that the systemic enzymatic activities are governed by attractors with capacity to store functional metabolic patterns which can be correctly recovered from specific input stimuli. The network attractors regulate the catalytic patterns, modify the efficiency in the connection between the multienzymatic complexes, and stably retain these modifications. Here for the first time, we have introduced the general concept of attractor metabolic network, in which this dynamic behavior is observed.
  • Used a Hopfield network via a Boltzman machine.

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0059196 Prenatal Exposure to a Polychlorinated Biphenyl (PCB) Congener Influences Fixation Duration on Biological Motion at 4-Months-Old: A Preliminary Study

  • infants exposed to PCBs have delayed / impaired development. Expected, but still sad.

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0060437 Hunger in the Absence of Caloric Restriction Improves Cognition and Attenuates Alzheimer's Disease Pathology in a Mouse Model

  • Ghrelin, a hunger-inducing drug attenuates AD pathology, in the absence of caloric restriction, and the neuroendocrine aspects of hunger also prevent age-related cognitive decline.

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ref: -0 tags: brain mapping recording Yuste date: 04-10-2013 19:31 gmt revision:1 [0] [head]

PMID-22726828 The Brain Activity Map Project and the Challenge of Functional Connectomics

  • They are more interested in every neuron within a local circuit, e.g. cortical column.
  • Referenced papers, optical:
    • Yuste et al 2011 -- referenced several times.
    • Helmchen 2011
    • Yuste and Katz 1991 (calcium)
    • Grienberger and Konnerth 2012 (1000 recorded neurons)
    • Peterka 2011 -- voltage imaging
    • Mochalin 2012 -- nanodiamonds.
  • The optical techniques only gets you .. 400um? 2mm?
    • Suggest GRIn objectives for invasive recording of the e.g. hippocampus.
  • Interesting: DNA polymerases could be used as spike sensors since their error rates are dependent on cation concentration.
    • use synthetic cells, then sequence the molecular recording.
  • The Drosophila connectome is currently 20% complete at the mesoscale (Chiang et al 2011)
    • Drosophila has 135,000 neurons
  • Bock et al 2011 have reconstructed 1,500 cell bodies with 1e13 pixels.
  • In the human genome project, every dollar invested generated $141 in the economy. (Battelle 2011).

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ref: -0 tags: brain mapping Deisseroth Donoghue widescale recording date: 04-10-2013 19:31 gmt revision:1 [0] [head]

PMID-23514423 Nanotools for Neuroscience and Brain Activity Mapping

  • human brain has roughly 85e9 neurons, 1e14 synapses, 100 neurotransmitters.
  • focus on novel nanoprobes.
  • Assuming a uniform connaction probability, the lielihood of finding synaptically coupled cells increases quadratically with N.
  • pretty high-level article.
  • Multiferroic antennas (?) -- must look this up!
  • Look up ref 146 -- microendoscope. Did they design the camera module?

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ref: -0 tags: dissertation interconnect parylene flexible electrodes date: 02-26-2013 00:30 gmt revision:2 [1] [0] [head]

http://docs.lib.purdue.edu/dissertations/AAI3444877/

  • Several different projects --
    • Stretchable PDMS electrodes
    • PDMS-parylene ECoG
    • Transmitting parallel neural data via free-space optical link
    • semi-flexible hydrogel-parylene neural electrode.
    • The parylene electrodes with selectively patterned hydrogel provide stiff mechanical properties for easy penetration into the brain tissues and subsequent flexibility after insertion upon swelling of the hydrogel.
    • advanced packaging system with using a composite inorganic parylene combination.
      • Atomic layer deposited alumina-zirconia (Al2O3–ZrO2) composite layer can provide a conformal and nano-laminated coating on parylene surface in neural packaging systems in order to improve the hermeticity for long term implantations
  • Can't get the entire PDF. annoying.

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ref: -0 tags: parylene interconnect monolithic integration silicon DRIE date: 02-26-2013 00:29 gmt revision:1 [0] [head]

A New Multi-Site Probe Array with Monolithically Integrated Parylene Flexible Cable for Neural Prostheses

    • Use DRIE to etch the back of the wafer after patterning the front. Clever!

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ref: -0 tags: parylene PDMS material properties gold compliant date: 02-08-2013 22:38 gmt revision:2 [1] [0] [head]

PMID-21240559 Highly-compliant, microcable neuroelectrodes fabricated from thin-film gold and PDMS

  • he microcable electrodes were also electromechanically tested, with measurable conductivity (220 kΩ) at an average 8% strain (n = 2) after the application of 200% strain.

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ref: -0 tags: hikes date: 02-08-2013 19:09 gmt revision:0 [head]

Bay area hikes:

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ref: Suner-2005.12 tags: Suner Utah probe electrophysiology reliability chronic electrode recording longevity histology MEA date: 01-31-2013 22:27 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

PMID-16425835Reliability of signals from a chronically implanted, silicon-based electrode array in non-human primate primary motor cortex

  • claim that they have done a logitudinal development series that included 39 array implants in 18 monkeys.
  • can get reliable recordings out to 3 months (only? probably the array was forced out of the brain?)
    • however, it seems that their recording quality did not decrease dramatically over those 3 months.
  • excellent methods section.
  • also {1027}

____References____

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ref: -0 tags: microelectrodes original metal pipette glass recording MEA date: 01-31-2013 19:46 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

IEEE-4065599 (pdf) Comments on Microelectrodes

  • The amplifiers themselves, even back in 1950's, posed no problems -- low bandwidth. All that is required is low noise and high input impedance.
  • KCl Glass electrodes are LPF (10M resistive + 10pf parasitic capacitance); metal HPF (capacitive).
    • The fluid tip will not see external triphasic spikes of vertebrate axons above the noise level.
  • Metal probe the most useful.
  • Pt electrode in CSF behaves like a capacitor at low voltage across a broad frequency range. CSF has compounds that retard oxidation; impedance is more resistive with physiological saline.
  • Noise voltage generated by a metal electrode best specified by equivalent noise resistance at room temperature, E rmsnoise=4kTR nδF R_n should equal the real part of the electrode impedance at the same frequency.
  • Much of electrochemistry: solid AgCl diffuses away from an electrode tip with great speed and can hardly be continuously formed with an imposed current. Silver forms extremely stable complexes with organic molecules having attached amino and sulfhydril groups which occur in plenty where the electrode damages the tissue. Finally, the reduction-oxidation potential of axoplasm is low enough to reduce methylene blue, which places it below hydrogen. AgCl and HgCl are reduced.
  • The external current of nerve fibers is the second derivative of the traveling spike, the familiar triphasic (??) transient.
  • Svaetichin [1] and Dowben and Rose [3] plated with Platinum black. This increases the surface area.
    • Very quickly it burns onto itself a shell of very adherent stuff. It is kept from intimate contact with the tissue around it by a shell.
    • We found that if we add gelatin to the chloroplatinic acid bath from which we plate the Pt, the ball is not only made adherent to the tip but is, in a sense, prepoisoned and does not burn a shell into itself.
  • glass insulation using woods metal (which melts at a very low temperature). Platinum ball was plated onto 2-3um pipette tip. 3um gelatinized platinum black ball, impedance 100kOhm at 1kHz.
    • Highly capacitive probe: can be biased to 1 volt by a polarizing current of 1e-10 amp. (0.1nA).
  • Getting KCl solution into 1um pipettes is quite hard! They advise vacuum boiling to remove the air bubbles.
  • Humble authors, informative paper.

____References____

' ''' ()

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ref: Ledochowitsch-2011.01 tags: Ledochowitsch transparent micro ECoG Peter date: 01-30-2013 07:01 gmt revision:2 [1] [0] [head]

PMID-22254956[0] A transparent μECoG array for simultaneous recording and optogenetic stimulation.

  • We present a 49-channel μECoG array with an electrode pitch of 800 μm and a 16-channel linear μECoG array with an electrode pitch of 200 μm.
  • The backing material was Parylene C. Transparent, sputtered indium tin oxide (ITO) was used in conjunction with e-beam evaporated gold to fabricate the electrodes

____References____

[0] Ledochowitsch P, Olivero E, Blanche T, Maharbiz MM, A transparent μECoG array for simultaneous recording and optogenetic stimulation.Conf Proc IEEE Eng Med Biol Soc 2011no Issue 2937-40 (2011)

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ref: -0 tags: polymide flexible electrode Rousche incision needle assist date: 01-30-2013 06:38 gmt revision:3 [2] [1] [0] [head]

PMID-11327505 Flexible Polyimide-Based Intracortical Electrode Arrays with Bioactive Capability

  • Use gold / polymide fabrication; electrode is 20um thick, 160um wide.
  • Still quite flexible -- buckles at 0.003 N.
  • Successfully recorded by inserting it in an incision in rat barrel cortex -- needle assist.
    • Well, not too successfully.
  • Suggest that bioactive components can be applied to the permeable polymide surface.

____References____

' ''' ()

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ref: Kruger-2010.05 tags: microelectrode array nichrome 7 years rhesus electrophysiology MEA Kruger oblique inverted date: 01-29-2013 07:54 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

PMID-20577628[0] Seven years of recording from monkey cortex with a chronically implanted multiple electrode.

  • Seven years!! good recordings the whole time, too. As they say, this is a clinically realistic time period. Have they solved the problem?
  • Used 12.5um Ni-Cr-Al wire insulated with 3um of polymide.
    • Wires were then glued to an 8x8 connector block using conductive epoxy.
    • Glued the bundle together with a solution of plexiglas in dichloroethane.
    • Then introduced the 0.3mm bundle into a j-shaped cannula. This allowed them to approach the gray matter inverted, from below (the white matter).
    • implanted 64 ch array into ventral premotor cortex (arm representation?).
  • No apparent degradation of recording quality over that time.
  • Had some serious problems with the quality of their connector.
    • They recommend: "Rather, the contacts on the head should be made from noble metals and be flat or shallowly hollow, so that they can be easily cleaned, and no male contacts can break."
    • Really need to amplify and multiplex prior connector (imho).
  • Claim that them managed to record from two neurons on one channel for nearly 7 years (ch 54).
  • They cite us, but only to indicate that we recommend slow penetration of the brain. They agree with our results that lowering of individual electrodes is better than all at once.

____References____

[0] Kruger J, Caruana F, Volta RD, Rizzolatti G, Seven years of recording from monkey cortex with a chronically implanted multiple microelectrode.Front Neuroengineering 3 Issue 6 (2010 May 28)

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ref: -0 tags: histology optical coherence tomography vasculature avoidance date: 01-29-2013 06:46 gmt revision:0 [head]

PMID-9766311 Optical coherence tomography for neurosurgical imaging of human intracortical melanoma.

  • Relevant for our interests: Subsurface cerebral vascular structures could be identified and were therefore avoided.
  • more broadly, could identify subsurface metastatic melanoma due to reflectance changes. nice.

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ref: Wester-2009.04 tags: parylene flexible electrode gold Georgia date: 01-29-2013 03:14 gmt revision:4 [3] [2] [1] [0] [head]

PMID-19255461[0] Development and characterization of in vivo flexible electrodes compatible with large tissue displacements.

  • Device was 100um wide and 25um thick, and was stiff enough to enter directly.
    • carefully calibrated this stiffness -- good! we should do the same.
  • parylene composition.
  • brain tissue force on the order of 2mN.
  • No histology.
  • [http://www.ncbi.nlm.nih.gov/pubmed?term=LaPlaca%20MC[Author]&cauthor=true&cauthor_uid=19255461 laPlaca] has a good number of publications on shear stress in brain tissue.

____References____

[0] Wester BA, Lee RH, LaPlaca MC, Development and characterization of in vivo flexible electrodes compatible with large tissue displacements.J Neural Eng 6:2, 024002 (2009 Apr)

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ref: Neary-2003.03 tags: histology astrocyte response date: 01-29-2013 01:02 gmt revision:1 [0] [head]

PMID-12657694[0] High rate shear strain of three-dimensional neural cell cultures: a new in vitro traumatic brain injury model.

  • Astrocytes have mechanoreceptors that induces ERK signaling.
    • ERK =extracellular signal-regulated protein kinase, a key regulator of cellular proliferation and differentiation.

____References____

[0] Neary JT, Kang Y, Willoughby KA, Ellis EF, Activation of extracellular signal-regulated kinase by stretch-induced injury in astrocytes involves extracellular ATP and P2 purinergic receptors.J Neurosci 23:6, 2348-56 (2003 Mar 15)

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ref: Polikov-2005.1 tags: neural response glia histology immune electrodes recording 2005 Tresco Michigan microglia date: 01-29-2013 00:34 gmt revision:10 [9] [8] [7] [6] [5] [4] [head]

PMID-16198003[0] Response of brain tissue to chronically implanted neural electrodes

  • Good review (the kind where figures are taken from other papers). Nothing terribly new (upon a very cursory inspection)
  • When CNS damage severs blood vessels, microglia are indistinguishable from the blood borne, monocyte-derived macrophages that are recruited by the degranulation of platelets and the cellular release of cytokines.
  • Furthermore, microglia are known to secrete, either constitutively, or in response to pathological stimuli, neurotrophic factors that aid in neuronal survival and growth.
    • Also release cytotoxic and neurotoxic factors that can lead to neuronal death in vitro.
    • It has been suggested that the presence of insoluble materials in the brain may lead to a state of 'frustrated phagocytosis' or inability of the macrophages to remove the foreign body, resulting in persistent release of neurotoxic substances.
  • When a 10x10 array of silicon probes was implanted in feline cortex, 60% of the needle tracks showed evidence of hemorrhage and 25% showed edema upon explantation of the probes after one day (Schmidt et al 1993) {1163}
    • Although a large number of the tracks were affected, only 3-5% of the area was actually covered by hemorrhages and edema, suggesting the actual damage to blood vessels may have been relatively minor. (!!)
  • Excess fluid and cellular debris diminishes 6-8 days due to the action of activated microglia and re-absorption.
  • As testament to the transitory nature of this mechanically induced wound healing response, electrode tracks could not be found in animals after several months when the electrode was inerted and quickly removed (Yuen and Agnew 1995, Rousche et al 2001; Csicsvari et al 2003, Biran et al 2005).
  • Biran et al 2005: observed persistent ED-1 immunoreactivity around silicon microelectrode arrays implanted in rat cortex at 2 and 4 weeks following implantation; not seen in microelectrode stab wound controls.
  • On the glial scar:
    • observed in the CNS of all vertebrates, presumably to isolate damaged parts of the nervous system and maintain the integrity of the blood-brain barrier.
    • mostly composed of reactive astrocytes.
    • presumably the glial scar insulates electrodes from nearby neurons, hindering diffusion and increasing impedance.
  • On the meninges:
    • Meningeal fibroblasts, which also stain for vimentin, but not for GFAP, may migrate down the electrode shaft from the brain surface and form the early basis for the glial scar.
  • On recording quality:
    • Histological examination upon explantation revealed that every electrode with stable unit recordings had at least one large neuron near the electrode tip, while every electrode that was not able to record resolvable action potentials was explanted from a site with no large neurons nearby.
  • Perhaps the clearest example of this variability was observed in the in vivo response to plastic “mock electrodes” implanted in rabbit brain by Stensaas and Stensaas (1976) {1210} and explanted over the course of 2 years. They separated the response into three types: Type 1 was characterized by little to no gliosis with neurons adjacent to the implant, Type 2 had a reactive astrocyte zone, and Type 3 exhibited a layer of connective tissue between the reactive astrocyte layer and the implant, with neurons pushed more than 100 um away. All three responses are well documented in the literature; however this study found that the model electrodes produced all three types of reactions simultaneously,depending on where along the electrode one looked.

____References____

[0] Polikov VS, Tresco PA, Reichert WM, Response of brain tissue to chronically implanted neural electrodes.J Neurosci Methods 148:1, 1-18 (2005 Oct 15)

{946}
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ref: Salcman-1976.01 tags: Salcman electrodes recording chronic microelectrode array MEA original parylene date: 01-28-2013 22:18 gmt revision:8 [7] [6] [5] [4] [3] [2] [head]

PMID-1256090[0] A new chronic recording intracortical microelectrode

  • maintain that tethering is the rational way to go: it "re-establishes the normal biomechanics of the intact cranial vault". (Salcman 1972, 1973) {1010}
    • have model of electrode tip motion in response to brain-skull displacements (Goldstein and Salcman 1973) {1011}
      • Electrode would have a tip displacement of about 5um in response to a 1mm displacement of the electrode's point of entry into the skull.
      • Exponential dependence on recording amplitude and distance (Rall, 1962). Gradient: 7.5uv/um; movements of more than 1-2um can radically alter the recordnig shape.
      • Probably our electrodes work because the dura & gliosis becomes firmly attached to the electrode shafts.
    • not really an array so much as a number (10-12) of single-unit electrodes.
  • Details the process of parylene-C deposition, electrode microwelding, etc. Pretty cool stuff -- what has happened to this technology?
  • Each bubble is glued with cyanocrylate to the pia. (they too question the safety of this).
  • arrays can be manually inserted via forceps.
  • 25um iridium wire electroplated in 1-2um of gold
    • then electo-etched until the desired tip geometry is achieved, 1-3um diameter
    • and vacuum coated in 3um of parylene-C.
    • Impedance 1-2M with a 1kHz sine wave at 10nA. Impedance is inversely related to the frequency of the test current, phase angle of 70-80deg.
      • Ref Robinson, 1968.
    • We must emphasize the extreme sensitivity of electrode measurements to the test conditions. Measured values of Z e are usually increased 1-3M when the electrode has been stored away for a few days. Removing the electrode from the test bath for a few minutes in air can lead to equally large increases when the electrode is tested upon remersion. [...] might be oxide.
    • Pinholes are the usual failure mechanism (KD Wise 2004), {149}; parylene is 'pinhole-free'.
  • The connecting 25um Au lead is very flexible and imposes little stress on the iridium electrode.
    • Connecting wire coated in 12um of parylene C
    • Would prefer even finer wire, 12um.
  • Perspex window over the craniotomy; had a vent in this window which they could open.
  • Opening the vent would cause the brain to pulse, moving the electrodes through the cortex and changing neural activity.
  • Size of an electrode is limited by ability to introduce it into the brain.
    • Electrode must be introduced through the pia; as the pial vessels supply the cortex (or drain the cortex).
    • For their electrodes, P crit=0.9g ; the force necessary to penetrate the pia is 0.05 - 0.2g.
  • pure iridium is stiffer than Pt-Ir by a factor of 3 or so. (521 G N/m^2 = 521 GPa, higher than tungsten, which is 400 Gpa)
    • Pure iridium is apparently the stiffest metallic element ref
  • Interesting: "Once again we are impressed by the fact that passive recording electrodes exhibit drops in impedance in the living system which they never show on in vitro testing in protein solutions at 37C.
    • Between 40 and 50 days, a slow downward trend becomes noticeable; this trend continues for the life of the animal and asymptotically approaches values below 500k. Electrodes still record.
    • See {999}
    • Surmise that pure iridium electrodes have a different metal-electrolyte interface than more conventional metals (Pl and W).
  • Mention that the ultimate purpose is for a neural prosthesis.
    • Their then use was for recordings from M1 in monkeys and V1 from cats. (Schmidt, Bak, McIntosh 1974)
  • Ref Wise et al {1012}.

____References____

[0] Salcman M, Bak MJ, A new chronic recording intracortical microelectrode.Med Biol Eng 14:1, 42-50 (1976 Jan)

{748}
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ref: Leung-2008.08 tags: biocompatibility alginate tissue response immunochemistry microglia insulation spin coating Tresco recording histology MEA date: 01-28-2013 21:19 gmt revision:4 [3] [2] [1] [0] [head]

PMID-18485471[0] Characterization of microglial attachment and cytokine release on biomaterials of differing surface chemistry

  • The important result is that materials with low protein-binding (e.g. alginate) have fewer bound microglia, hence better biocompatibility. It also seems to help if the material is highly hydrophilic.
    • Yes alginate is made from algae.
  • Used Michigan probes for implantation.
  • ED1 = pan-macrophage marker.
    • (quote:) Quantification of cells on the surface indicated that the number of adherent microglia appeared higher on the smooth side of the electrode compared to the grooved, recording site side (Fig. 2B), and declined with time. However, at no point were electrodes completely free of attached and activated microglial cells nor did these cells disappear from the interfacial zone along the electrode tract.
    • but these were not coated with anything new .. ???

____References____

[0] Leung BK, Biran R, Underwood CJ, Tresco PA, Characterization of microglial attachment and cytokine release on biomaterials of differing surface chemistry.Biomaterials 29:23, 3289-97 (2008 Aug)

{1221}
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ref: Chestek-2011.08 tags: shenoy Utah array reliability recording BMI date: 01-28-2013 20:54 gmt revision:2 [1] [0] [head]

PMID-21775782[0] Long-term stability of neural prosthetic control signals from silicon cortical arrays in rhesus macaque motor cortex (Shenoy)

  • Overall, this study suggests that action potential amplitude declines more slowly than previously supposed, and performance can be maintained over the course of multiple years when decoding from threshold-crossing events rather than isolated action potentials.
  • During most time periods, decoder performance was not well correlated with action potential amplitude (p > 0.05 for three of four arrays)
    • Perhaps we are chasing the wrong dragon?
    • Still, minimal invasiveness / more channels is useful.

____References____

[0] Chestek CA, Gilja V, Nuyujukian P, Foster JD, Fan JM, Kaufman MT, Churchland MM, Rivera-Alvidrez Z, Cunningham JP, Ryu SI, Shenoy KV, Long-term stability of neural prosthetic control signals from silicon cortical arrays in rhesus macaque motor cortex.J Neural Eng 8:4, 045005 (2011 Aug)

{1036}
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ref: -0 tags: decoding recording todo read biocompatibility histology electrodes future date: 01-28-2013 20:52 gmt revision:9 [8] [7] [6] [5] [4] [3] [head]

Things to read!

decoding:

  • PMID-20359500 Population decoding of motor cortical activity using a generalized linear model with hidden states
  • Robust satisficing linear regression: Performance/robustness trade-off and consistency criterion
  • PMID-15813408 Closed-loop cortical control of direction using support vector machines
  • Efficient Decoding With Steady-State Kalman Filter in Neural Interface Systems
    • Fixed gain: We analyze a low-complexity Kalman filter implementation in which the filter gain is approximated by its steady-state form, computed offline before real-time decoding commences.
    • We also find that the steady-state Kalman filter reduces the computational load (algorithm execution time) for decoding the firing rates of 25±3 single units by a factor of 7.0±0.9.

electrodes:

other random scribblings: Vascularization {1027} histology {736},{737} and size {1028},{747},{1026}, insulation {1033}. How very very important -- as important or moreso than the recording technology. What has happened to {149} ?

{1028}
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ref: Szarowski-2003.09 tags: Michigan array silicon histology MEA cornell date: 01-28-2013 20:47 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

PMID-12914963[0] Brain responses to micro-machined silicon devices.

  • Used 2 different implants (rough & sharp corners, smooth), 2 different ways of inserting (slow, by hand).
    • Neither made much diff.
  • Measured GFAP = glial fibrillary acidic protein, a standard measure for assesing reactive gliosis [44,18,28,33,35].
    • Normally larger astrocytes were seen around larger blood vessels.
    • "At four weeks, a clear sheath of GFAP-positive astrocytes was observed"
    • GFAP labeled sheath seems to have plateaued at 6 weeks. (The sheath may be useful for our devices... )
  • Measured Vimentin, which is increased in reactive astrocytes and is not normally expressed in mature astrocytes [6,12,15,40].
    • In control animals vimentin only present in ependymal lining of the ventricles.
    • At 6 weeks, sites around both types of devices had a compact sheath of vimentin-positive astrocytes 50-100um.
    • Seemed to be a plateau as with GFAP .. though it seems to label a slightly distinct set of cells.
  • Also labeled reactive microglia with ED1 [4,19,27,36].
  • Quote: These data indicate that device insertion promotes two responses-an early response that is proportional to device size and a sustained response that is independent of device size, geometry, and surface roughness. The early response may be associated with the amount of damage generated during insertion. The sustained response is more likely due to tissue-device interactions.

____References____

[0] Szarowski DH, Andersen MD, Retterer S, Spence AJ, Isaacson M, Craighead HG, Turner JN, Shain W, Brain responses to micro-machined silicon devices.Brain Res 983:1-2, 23-35 (2003 Sep 5)

{1220}
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ref: -0 tags: histology review electrode response bioactive coatings date: 01-28-2013 20:16 gmt revision:0 [head]

PMID-20577634 Biocompatibility of intracortical microelectrodes: current status and future prospects.

  • ... but the most widely used method to enhance biocompatibility is the chemical modification of neural probe surfaces with anti-inflammatory compounds, adhesion proteins, or bioactive molecules (Heiduschka and Thanos, 1998; He et al., 2006; Ludwig et al., 2006; Moxon et al., 2007; Rennaker et al., 2007; Seymour and Kipke, 2007; Zhong and Bellamkonda, 2007; Leung et al., 2008; Williams, 2008; Grill et al., 2009)
    • Have any of these achieved success?
    • Many other polymers are basically biocompatible, provided they still insulate after equilibriating with the surrounding vapor pressure.
    • Personally I don't think biocoatings wil lmatter much if there is persistent shear at the interface.
  • Does make sense to have the electrode surface attractive to neurons (Kennedy..). For a later date.

{1219}
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ref: Williams-2007.12 tags: electrode impedance spectroscopy histology date: 01-28-2013 19:12 gmt revision:3 [2] [1] [0] [head]

PMID-18057508[0] Complex impedance spectroscopy for monitoring tissue responses to inserted neural implants.

  • In general, impedance magnitude at 1 kHz was significantly increased in extensive reactions, starting about 4 days post-implant
    • Impedance is hence predictive of performance.
  • Electrodes with extensive reactions also displayed impedance spectra with a characteristic change at high frequencies. This change was manifested in the formation of a semi-circular arc in the Nyquist space, suggestive of increased cellular density in close proximity to the electrode site.
    • Interesting! Usefull!

____References____

[0] Williams JC, Hippensteel JA, Dilgen J, Shain W, Kipke DR, Complex impedance spectroscopy for monitoring tissue responses to inserted neural implants.J Neural Eng 4:4, 410-23 (2007 Dec)

{1201}
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ref: Kato-2006.01 tags: bioactive neural probes flexible parylene japan Kato microspheres date: 01-28-2013 03:57 gmt revision:1 [0] [head]

PMID-17946847[0] Preliminary study of multichannel flexible neural probes coated with hybrid biodegradable polymer.

  • Conference proceedings. a little light.
  • :-)
  • probes made of parylene-C

____References____

[0] Kato Y, Saito I, Hoshino T, Suzuki T, Mabuchi K, Preliminary study of multichannel flexible neural probes coated with hybrid biodegradable polymer.Conf Proc IEEE Eng Med Biol Soc 1no Issue 660-3 (2006)

{1177}
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ref: -0 tags: magnetic flexible insertion japan neural recording electrodes date: 01-28-2013 03:54 gmt revision:2 [1] [0] [head]

IEEE-1196780 (pdf) 3D flexible multichannel neural probe array

  • Shoji Takeuchi1, Takafumi Suzuki2, Kunihiko Mabuchi2 and Hiroyuki Fujita
  • wild -- they use a magnetic field to make the electrodes stand up!
  • Electrodes released with DRIE, as with Michigan probes.
  • As with many other electrodes, pretty high electrical impedance - 1.5M @ 1kHz.
    • 20x20um recording sites on 10um parylene.
  • Could push these into a rat and record extracellular APs, but nothing quantitative, no histology either.
  • Used a PEG coating to make them stiff enough to insert into the ctx (phantom in IEEE conference proceedings.)

{1217}
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ref: Bjornsson-2006.09 tags: micro vasculature histology insertion speed tissue shear date: 01-28-2013 03:38 gmt revision:3 [2] [1] [0] [head]

PMID-16921203[0] Effects of insertion conditions on tissue strain and vascular damage during neuroprosthetic device insertion.

  • We have developed an ex vivo preparation to capture real-time images of tissue deformation during device insertion using thick tissue slices from rat brains prepared with fluorescently labeled vasculature.
  • Direct damage to the vasculature included severing, rupturing and dragging, and was often observed several hundred micrometers from the insertion site. (yikes!)
  • Advocate faster insertion of sharp devices. (tatoo needle?).
  • Cortical surface features greatly affected insertion success; insertions attempted through pial blood vessels resulted in severe tissue compression.
    • Thus, avoiding vasculature is useful not only for avoiding hemorrhaging, but also to prevent excessive tissue compression.
  • High degree of variability
    • Indicates that this should be measured! Scientifically interesting!
  • Insertion speeds:
    • Fast 2 mm/sec
    • Medium 500 um/sec
    • Slow 125 um/sec
  • Perhaps there is no need to experiment with multiple insertion speeds?

____References____

[0] Bjornsson CS, Oh SJ, Al-Kofahi YA, Lim YJ, Smith KL, Turner JN, De S, Roysam B, Shain W, Kim SJ, Effects of insertion conditions on tissue strain and vascular damage during neuroprosthetic device insertion.J Neural Eng 3:3, 196-207 (2006 Sep)

{1200}
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ref: Kim-2004.05 tags: histology electrode immune response Tresco hollow fiber membranes GFAP vimentin ED1 date: 01-28-2013 03:08 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

PMID-14741588[0] Chronic response of adult rat brain tissue to implants anchored to the skull.

  • The increase in tissue reactivity observed with transcranially implanted HFMs may be influenced by several mechanisms including chronic contact with the meninges and possibly motion of the device within brain tissue.
  • Broadly speaking, our results suggest that any biomaterial, biosensor or device that is anchored to the skull and in chronic contact with meningeal tissue will have a higher level of tissue reactivity than the same material completely implanted within brain tissue.
  • See also [1]
  • Could slice through the hollow fiber membrane for histology. (as we shall).
  • Good list of references.

____References____

[0] Kim YT, Hitchcock RW, Bridge MJ, Tresco PA, Chronic response of adult rat brain tissue to implants anchored to the skull.Biomaterials 25:12, 2229-37 (2004 May)
[1] Biran R, Martin DC, Tresco PA, The brain tissue response to implanted silicon microelectrode arrays is increased when the device is tethered to the skull.J Biomed Mater Res A 82:1, 169-78 (2007 Jul)

{895}
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ref: XindongLiu-2006.03 tags: neural recording electrodes stability cat parlene McCreery MEA date: 01-28-2013 02:50 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

IEEE-1605268 (pdf) Evaluation of the Stability of Intracortical Microelectrode Arrays

  • 35-50um IR electrodes, electrolytically sharpened at a 10 deg angle, with a 5um blunted tip.
  • Electrodes coated in parylene, and exposed at the tip with an eximer laser. Surface area of tip ~500um^2.
  • Sorted based on features (duration, pk-pk, ratio of + to -, ratio of + time to - time), followed by a demixing matrix (PCA?)
  • Did experiments in 25 cats with some task (for another paper?); got recordings for up to 800 days. Seems consistent with our results.
  • Neurons were stable (by their metrics) for up to 60 days.
  • sparse arrays showed stable recordings sooner than dense arrays, perhaps because they are larger and more qucikly become attached to the dura.
  • Electrodes were always unstable for the first 2-3 months. Stability index is as high as 30-40 days.
  • Average electrode yield was ~ 25%.
  • no histology.

____References____

Xindong Liu and McCreery, D.B. and Bullara, L.A. and Agnew, W.F. Evaluation of the stability of intracortical microelectrode arrays Neural Systems and Rehabilitation Engineering, IEEE Transactions on 14 1 91 -100 (2006)

{1114}
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ref: Feingold-2012.04 tags: Feingold Graybeil electrode moveable recording date: 01-28-2013 02:13 gmt revision:1 [0] [head]

PMID-22170970[0] A system for recording neural activity chronically and simultaneously from multiple cortical and subcortical regions in non-human primates.

  • Up to 127 electrodes in 14 brain areas for up to a year at a time.

____References____

[0] Feingold J, Desrochers TM, Fujii N, Harlan R, Tierney PL, Shimazu H, Amemori K, Graybiel AM, A system for recording neural activity chronically and simultaneously from multiple cortical and subcortical regions in nonhuman primates.J Neurophysiol 107:7, 1979-95 (2012 Apr)

{898}
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ref: Ward-2009.07 tags: microelectrode arrays immune response recording MEA Purdue date: 01-28-2013 01:52 gmt revision:8 [7] [6] [5] [4] [3] [2] [head]

PMID-19486899[0] Toward a comparison of microelectrodes for acute and chronic recordings.

  • Good research, paper well written.
  • Results suggest significant variability within and between microelectrode types with no clearly superior array (from the abstract).
  • As Miguel mantains, "Much of the new technology, however, does not supersede traditional microwire technology in its ability to evade a host immune response".
  • Initial implantation wound initiates a cascade of immune responses which culminates in a sheath of microglia, astrocytes, various ectracellular matrix constituents, and macrophages.
    • Decent citation list -- many people have been working on MEAs.
  • Fibrous encapusulation of the electrode is much less conductive than healthy nervous tissue, hence impedance measurements can be used to track tissue response.
  • Used Osort to sort the recorded neurons.
  • "Despite differing implant locations, and thus potentially differing levels of background neural activity, and differing scarring responses, which relates to the level of thermal noise in the observed signal (Ludwig et al., 2006), no significant SNR differences were observed among the MEA types for the duration of the study."
  • SNR trends did not seem to relate to site impedance trends over the 31-day period, and by inference, the extent of tissue encapsulation and neuronal density loss.
    • SNR is likely controlled by background neural noise, not thermal noise (which would be linked to impedance).
  • Electrodes with lower impedance generally recorded units from more sites than arrays with higher impedance.

____References____

[0] Ward MP, Rajdev P, Ellison C, Irazoqui PP, Toward a comparison of microelectrodes for acute and chronic recordings.Brain Res 1282no Issue 183-200 (2009 Jul 28)

{1214}
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ref: -0 tags: brain micromotion magnetic resonance imaging date: 01-28-2013 01:38 gmt revision:0 [head]

PMID-7972766 Brain and cerebrospinal fluid motion: real-time quantification with M-mode MR imaging.

  • Measured brain motion via a clever MR protocol. (beyond my present understanding...)
  • ventricles move at up to 1mm/sec
  • In the Valsava maneuver the brainstem can move 2-3mm.
  • Coughing causes upswing of the CSF.

{1213}
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ref: Chhatbar-2010.05 tags: Lee von Kraus Francis SUNY downstate electrode floating headpost date: 01-28-2013 01:06 gmt revision:1 [0] [head]

PMID-20153370[0] A bio-friendly and economical technique for chronic implantation of multiple microelectrode arrays

  • Nesting design -- the headpost is the only transcutaneous object.

____References____

[0] Chhatbar PY, von Kraus LM, Semework M, Francis JT, A bio-friendly and economical technique for chronic implantation of multiple microelectrode arrays.J Neurosci Methods 188:2, 187-94 (2010 May 15)

{78}
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ref: Musallam-2007.02 tags: Musallam MEA floating rats electrodes date: 01-28-2013 00:42 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

PMID-17067683[0] A floating metal microelectrode array for chronic implantation

  • Cite Gualtierotti and Bailey (1968) for a neutral-boyancy electrode w/ rigid shaft.
  • Alumina ceramic base, laser drilled.
  • insulated with silane follwed by parylene-C, 3um.
  • Tips exposed by eximer laser. (Schmidt et al, 1995)
  • Electrophysiology, but not histology.
  • Earlier conference proceedings: PMID-17946982[1] Active floating micro electrode arrays (AFMA).

____References____

[0] Musallam S, Bak MJ, Troyk PR, Andersen RA, A floating metal microelectrode array for chronic implantation.J Neurosci Methods 160:1, 122-7 (2007 Feb 15)
[1] Kim T, Troyk PR, Bak M, Active floating micro electrode arrays (AFMA).Conf Proc IEEE Eng Med Biol Soc 1no Issue 2807-10 (2006)

{311}
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ref: Westby-1997.1 tags: recording microwire electrode MEA sweet sucrose saliva dissolving FET floating date: 01-28-2013 00:28 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-9350963 A floating microwire technique for multichannel neural recording and stimulation in the awake rat

  • sweet electrodes -- attached to glass micropipette with sucrose or saliva.
    • Chorover and DeLuca 1972 "A sweet new multiple electrode for chronic single unit recording". {1019}
  • 42 implanted rats, 252 implanted wires, 79% yield. 62% of electrodes still working at 5 weeks.
    • Targeting an area with really large somas (50um).
  • fully-floating 25um microwire ellectrodes.
  • platinum iridium, 25um, teflon coated, handled only with silastic-protected pliers & tweezers to prevent damage to the insulation.
  • electrode impdance range 200-900kOhms; check insulation by applying -3V to each electrode & looking for hydrogen bubbles.
  • soldering hardens platinum iridium alloy (huh).
  • (!!!) wires are stiffened for implantation by temporarily attaching them to a micropipette guide with sucrose which subsequently dissolves in the brain!
  • the smooth sucrose (40 grams in 50ml of water heated to 118C) coating requires about a week of desiccation to become hard enough for insertion into the brain without premature softening. Sucrose becomes clear like glass once fully desiccated.
  • the air above the craniotomy is sufficiently humid to dissolve the sucrose if left there for more than a few seconds.
  • used a miniature single-channel FET amplifier as a headstage - only one channel out of 6 could be recorded at once :( Thus their reults only apply to the best of the microwires implanted - not to all of them.
  • recorded onto a mac quadra (hahah) 20khz 12 bit
  • applying 160ua microstimulation pulses can restore low (200kohm) electrode impedance. Recording quality was generally improved for a few days following stimulation but then returned to an asymptotic level with the impedance at approximately 900kOhm.
  • electrodes only seemed to last 5 weeks, whence they declined to about 27% yeild - see figure 8.
  • good review of microelectrode recording up to that point (1997).

____References____

{1105}
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ref: Bullara-1983.09 tags: electrode grinding insulation stimulation date: 01-28-2013 00:27 gmt revision:1 [0] [head]

PMID-6632958[0] A microelectrode for delivery of defined charge densities.

  • Details the diamond impregnated lead grinding and epoxy insulation of 75um Pt-Ir wires;
  • Encapsulate the whole thing in Dacron mesh;
  • Electrodes are good for stimulating up to 300 uC / cm^2 * phase;
  • Charge balanced pulses 5-20ua in amplitude, 200us/phase, 20Hz repetition are sufficient to activate nearby cortical neurons.

____References____

[0] Bullara LA, McCreery DB, Yuen TG, Agnew WF, A microelectrode for delivery of defined charge densities.J Neurosci Methods 9:1, 15-21 (1983 Sep)

{736}
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ref: Liu-1999.09 tags: electrodes recording tissue response MEA histology date: 01-28-2013 00:24 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

PMID-10498377[0] Stability of the interface between neural tissue and chronically implanted intracortical microelectrodes.

  • implanted 7-shaft 35um iridium electrodes into the pericruciate gyrus of cats & measured the stability of recordings over several months.
  • electrodes were floating, under the dura; they note that connective tissue can force these floating arrays out of the brain, in further, or can encapsulate the electrodes.
    • electrodes activated by 'potentiodynamic cycling' to remove the insulation from the tip, I guess.
    • Insulation is epoxylite epoxy (5-10um thick) which is baked for curing and degassing at 100 and 170C each for 30 minutes.
    • more information on their fabrication in {1105}
  • Used the now-standard techniques for recording & analysis - amazing that this was all very new 10 years ago!
  • Measure stability not only on waveform shape (which will change as the position of the electrode relative to the neuron changes) but also neural tuning.
  • Lymphocytes were found to accumulate around the tips of the microstimulated sites.
  • Electrode sites that yielded recordings ('active') were all clean, with large neurons near the end, and with minimal connective tissue sheath (2-8 um; distance to nearby neurons was 30-50um).
    • Longest period for an active electrode was 242 days.
    • Electrode impedance was usually between 50 and 75 kOhm; there was no insulation failure.
  • Electrodes were stable even when the cat vigorously shook it's head in response to water placed on the head (!).
  • Electrodes were very unstable the first 2 weeks - 1 month ; rather stable thereafter.
    • Active electrodes tended to remain active ; inactive electrodes tended to remain inactive.

____References____

[0] Liu X, McCreery DB, Carter RR, Bullara LA, Yuen TG, Agnew WF, Stability of the interface between neural tissue and chronically implanted intracortical microelectrodes.IEEE Trans Rehabil Eng 7:3, 315-26 (1999 Sep)
[1] Bullara LA, McCreery DB, Yuen TG, Agnew WF, A microelectrode for delivery of defined charge densities.J Neurosci Methods 9:1, 15-21 (1983 Sep)

{1195}
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ref: Stevenson-2011.02 tags: Kording neural recording doubling northwestern chicago date: 01-28-2013 00:12 gmt revision:1 [0] [head]

PMID-21270781[0] How advances in neural recording affect data analysis.

  • Number of recorded channels doubles about every 7 years (slowish).
  • "Emerging data analysis techniques should consider both the computational costs and the potential for more accurate models associated with this exponential growth of the number of recorded neurons."

____References____

[0] Stevenson IH, Kording KP, How advances in neural recording affect data analysis.Nat Neurosci 14:2, 139-42 (2011 Feb)

{746}
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ref: Sanders-2000.1 tags: polymer fiber immune reaction biocompatibility rats polycaprolactone recording electrodes histology MEA date: 01-28-2013 00:01 gmt revision:11 [10] [9] [8] [7] [6] [5] [head]

PMID-10906696[0] Tissue response to single-polymer fibers of varying diameters: evaluation of fibrous encapsulation and macrophage density.

  • Fibers smaller than 6μm show reduced immune response.
    • Fibers implanted in the subcutaneous dorsum (below the skin in the back of rats).
    • Polypropylene. (like rope).
    • Wish the result extended to small beads & small electrodes. 7μm is tiny, but possible with insulated Au wires.
      • Beads: try PMID-1913150 -- shows that the 600um - 50um beads ('microspheres') are well tolerated.
      • Also {750}.
  • Macrophage density in tissue with fiber diameters 2.1-5.9um comparable to that of unoperated contralateral control.

"

fiber diametercapsule thickness
2.1-5.90.6
6.5-10.611.7
11.1-15.820.3
16.7-26.725.5

____References____

[0] Sanders JE, Stiles CE, Hayes CL, Tissue response to single-polymer fibers of varying diameters: evaluation of fibrous encapsulation and macrophage density.J Biomed Mater Res 52:1, 231-7 (2000 Oct)

{1211}
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ref: Harris-1998.08 tags: noise wolpert harris motor planning Fitt velocity variance control theory date: 01-27-2013 22:33 gmt revision:1 [0] [head]

PMID-9723616[0] Signal-dependent noise determines motor planning.

  • We present a unifying theory of eye and arm movements based on the single physiological assumption that the neural control signals are corrupted by noise whose variance increases with the size of the control signal
    • Poisson noise? (I have not read the article -- storing here for future reference.)
  • This minimum-variance theory accurately predicts the trajectories of both saccades and arm movements and the speed-accuracy trade-off described by Fitt's law.

____References____

[0] Harris CM, Wolpert DM, Signal-dependent noise determines motor planning.Nature 394:6695, 780-4 (1998 Aug 20)

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ref: bookmark-0 tags: intrinsic evolution FPGA GPU optimization algorithm genetic date: 01-27-2013 22:27 gmt revision:1 [0] [head]

!:

  • http://evolutioninmaterio.com/ - using FPGAs in intrinsic evolution, e.g. the device is actually programmed and tested.
  • - Adrian Thompson's homepage. There are many PDFs of his work on his homepage.
  • Parallel genetic algorithms on programmable graphics hardware
    • basically deals with optimizing mutation and fitness evaluation using the parallel arcitecture of a GPU: larger populations can be evaluated at one time.
    • does not concern the intrinsic evolution of algorithms to the GPU, as in the Adrian's work.
    • uses a linear conguent generator to produce random numbers.
    • used a really simple problem: Colville minimization problem which need only search through a four-dimensional space.
  • Cellular genetic algoritms and local search for 3-SAT problem on Graphic Hardware
    • concerning SAT: satisfiabillity technique: " many practical problems, such as graph coloring, job-shop scheduling, and real-world scheduling can be represented as a SAT problem.
    • SAT-3 refers to the length of the search clause. length 3 is apparently very hard..
    • they use a combination of greedy search (flip the bit that increases the fitness the largest ammount) and random-walk via point mutations to keep the algorithm away from local minima.
    • also use cellular genetic algorithm which works better on a GPU): select the optimal neignbor, not global, individual.
    • only used a GeForce 6200 gpu, but it was still 5x faster than a p4 2.4ghz.
  • Evolution of a robot controller using cartesian genetic programming
    • cartesian programming has many advantages over traditional tree based methods - e.g. blot-free evolution & faster evolution through neutral search.
    • cartesian programming is characterized by its encoding of a graph as a string of integers that represent the functions and connections between graph nodes, and program inputs and outputs.
      • this encoding was developed in the course of evolving electronic circuits, e.g. above ?
      • can encode a non-connected graph. the genetic material that is not utilized is analogous to biological junk DNA.
    • even in converged populations, small mutations can produce large changes in phenotypic behavior.
    • in this work he only uses directed graphs - there are no cycles & an organized flow of information.
    • mentions automatically defined functions - what is this??
    • used diffusion to define the fitness values of particular locations in the map. the fewer particles there eventually were in a grid location, the higher the fitness value of the robot that managed to get there.
  • Hardware evolution: on the nature of artifically evolved circuits - doctoral dissertation.
    • because evolved circuits utilize the parasitic properties of devices, they have little tolerance of the value of components. Reverse engineering of the circuits evolved to improve tolerance is not easy.

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ref: Harris-2011.08 tags: microelectrodes nanocomposite immune response glia recording MEA date: 01-27-2013 22:19 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-21654037[0] In vivo deployment of mechanically adaptive nanocomposites for intracortical microelectrodes

  • J P Harris, A E Hess, S J Rowan, C Weder, C A Zorman, D J Tyler and J R Capadona Case Western University.
  • Simple idea: electrodes should be rigid enough to penetrate the brain, yet soft enough to not damage it once implanted.
  • Many studies have shown that shear stress around a microelectrode shaft causes neural die-off and glial response.
  • You can only record from neurons if they are < 100um from the electrode tip.
  • Nanocomposite material is inspired by sea cucumber skin.
    • Our materials exhibit this behaviour by mimicking the architecture and proposed switching mechanism at play in the sea cucumber dermis by utilizing a polymer NC consisting of a controllable structural scaffold of rigid cellulose nanofibres embedded within a soft polymeric matrix. When the nanofibres percolate, they interact with each other through hydrogen bonding and form a nanofibre network that becomes the load-bearing element, leading to a high overall stiffness of the NC. When combined with a polymer system which additionally undergoes a phase transition at physiologically relevant temperatures, a contrast of over two orders of magnitude for the tensile elastic modulus is exhibited.
  • Probes were 200um wide, 100um thick, and had a point sharpened to 45deg.
  • Buckle force testing was done on 53um thick, 125um wide probes sharpened to a 30deg point.
  • Penetration stress through the rat pia is 1.2e7 dynes/cm^2 for a Si probe 40um thick and 80um wide.
  • See also {1198}

____References____

[0] Harris JP, Hess AE, Rowan SJ, Weder C, Zorman CA, Tyler DJ, Capadona JR, In vivo deployment of mechanically adaptive nanocomposites for intracortical microelectrodes.J Neural Eng 8:4, 046010 (2011 Aug)

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ref: Menei-1994.09 tags: microspheres beads polycaprolactone biocompatible drug delivery histology date: 01-27-2013 20:54 gmt revision:3 [2] [1] [0] [head]

PMID-7814435 Fate and biocompatibility of three types of microspheres implanted into the brain.

  • microspheres ( 24μm ) appear to be engulfed or surrounded by histocytic cells.
  • poly(e-caprolactone), which is supposed to be biodegradable, did not dissolve in the brain. The polymer is hydrophobic.
  • 20um spheres could be engulfed by macrophages; their microspheres were too large, and were encapsulated in a thin coallagen layer and astrocytic process.
  • no scale bars - annoying - but we can estimate the size of the coating to be about the same size as the beads themselves.

{1210}
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ref: Stensaas-1976.01 tags: histology implant electrodes immune response date: 01-25-2013 02:52 gmt revision:1 [0] [head]

PMID-782142[0] The reaction of the cerebral cortex to chronically implanted plastic needles.

  • Three different classes of result:
    • Type I is characterized by little or no gliosis and synapses within 1-5mu of the implant;
    • type II contains a pronounced zone of reactive astrocytes;
    • type III is typified by a zone of connective tissue near the implant surface
      • One implant can evince all 3 different types!
  • Already were thinking of neuroprosthetic devices.

____References____

[0] Stensaas SS, Stensaas LJ, The reaction of the cerebral cortex to chronically implanted plastic needles.Acta Neuropathol 35:3, 187-203 (1976)

{1027}
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ref: Suner-2005.12 tags: MEA Utah reliability longevity SNR date: 01-25-2013 02:03 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

PMID-16425835[0] Reliability of signals from a chronically implanted, silicon-based electrode array

  • see {597}
  • Percutaneous connector used pressure-fitted pogo pins, as Gary was thinking of.
  • Utah array coated in parylene for this exp.
    • After implantation, array and cortex was covered in gore-tex (to prevent dura adhesion) -- they do not highlight this fact.
  • polyester insulated 25um gold wires as leads.
  • Reasonable SNR over 82, 172, 154 days.
  • One monkey had an array to 569 days -- 76 electrodes still provided good or fair waveforms.
  • ancilary (?) measure of tuning of the neurons. most neurons were not tuned.
  • SNR calculated as peak-peak of waveform divided by 2x standard deviation of signal.
  • A total of 36 implants in 16 other monkeys, which were not systematically evaluated for reliability here, provided successful recordings for up to 1264 days. Most of these studies ended because of headcap failure.
    • They no longer use dental acrylic -- only titanium bone screws.
  • 50-800K impedance
  • Improvement of the signal quality and increased yield, for which there was no clear trend in the three animals, may result from recovery produced by variations in the initial insertion injury.
  • The cortical capillary bed is densely packed, with spacing on the order of 40um in primate cortical tissue [27] ( vasculature ) -- they suppose that variance may be due to this.

____References____

[0] Suner S, Fellows MR, Vargas-Irwin C, Nakata GK, Donoghue JP, Reliability of signals from a chronically implanted, silicon-based electrode array in non-human primate primary motor cortex.IEEE Trans Neural Syst Rehabil Eng 13:4, 524-41 (2005 Dec)

{1196}
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ref: Skousen-2011.01 tags: electrodes immune response Tresco Wise Michigan histology GFAP atrocyte surface area foreign body response date: 01-25-2013 01:44 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-21867802[0] Reducing surface area while maintaining implant penetrating profile lowers the brain foreign body response to chronically implanted planar silicon microelectrode arrays.

  • We studied the chronic brain foreign body response to planar solid silicon microelectrode arrays and planar lattice arrays with identical penetrating profiles but with reduced surface area in rats after an 8-week indwelling period.
  • Using quantitative immunohistochemistry, we found that presenting less surface area after equivalent iatrogenic injury is accompanied by significantly less
    • persistent macrophage activation,
    • decreased blood brain barrier leakiness,
    • and reduced neuronal cell loss.
  • Could be a factor of micromotion, too -- the lattice array has more anchoring points (?)
  • They propose it's a factor of TNF- α concentration around the implants. This, and other proinflammatory and cytoxic cytokines, is released by macrophages.
  • "Recent studies from our lab have described disruption of BBB integrity, indicated by the presence of autologous IgG in the brain parenchyma, surrounding both microwire and planar silicon recording devices ([1][2]. Under normal conditions, autologous IgG is excluded from the brain parenchyma (Azzi et al., 1990; Seitz et al., 1985) but has been observed following BBB disruption (Aihara et al., 1994).
    • E.g. the presence of IgG proves that the BBB was compromised.
      • Less so with the lattice implants.
  • Previous work from our lab using single microwires and single shaft, planar silicon microelectrode arrays indicated that the spatial distribution of GFAP does not increase with time over the indwelling period and did not support the “increase in astrogliosis over time hypothesis” as a dominant or general biologically related failure mechanism for this type of microelectrode recording device {1197}.

____References____

[0] Skousen JL, Merriam SM, Srivannavit O, Perlin G, Wise KD, Tresco PA, Reducing surface area while maintaining implant penetrating profile lowers the brain foreign body response to chronically implanted planar silicon microelectrode arrays.Prog Brain Res 194no Issue 167-80 (2011)
[1] Winslow BD, Christensen MB, Yang WK, Solzbacher F, Tresco PA, A comparison of the tissue response to chronically implanted Parylene-C-coated and uncoated planar silicon microelectrode arrays in rat cortex.Biomaterials 31:35, 9163-72 (2010 Dec)
[2] Winslow BD, Tresco PA, Quantitative analysis of the tissue response to chronically implanted microwire electrodes in rat cortex.Biomaterials 31:7, 1558-67 (2010 Mar)

{1198}
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ref: Harris-2011.12 tags: mechanically adaptive electrodes implants case western dissolving flexible histology Harris date: 01-25-2013 01:39 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-22049097[0] Mechanically adaptive intracortical implants improve the proximity of neuronal cell bodies.

  • See also [1]
  • Initial tensile modulus of 5GPa dropped to 12MPa. (almost 500-fold!)
    • Their polymer nanocomposite (NC) still swells 65-70% (with water?)
    • Implant size 100 x 200um.
  • Controlled with tungsten of identical size and coating.
  • Tethered to skull.
  • Interesting:
    • The neuronal nuclei density within 100 µm of the device at four weeks post-implantation was greater for the compliant nanocomposite compared to the stiff wire.
    • At eight weeks post-implantation, the neuronal nuclei density around the nanocomposite was maintained, but the density around the wire recovered to match that of the nanocomposite.
    • Hypothesis, in discussion: softer implants are affecting the time-course of the response rather that final results
  • The glial scar response to the compliant nanocomposite was less vigorous than it was to the stiffer wire
  • Cultured astrocytes have been shown to respond to mechanical stimuli via calcium signaling (Ostrow and Sachs, 2005).
  • Substrate stiffness is also known to shift cell differentiation in mesenchymal stem cells to be neurogenic, myogenic, or osteogenic (Engler et al., 2006).
  • In vivo studies which focus on the effects of electrode tethering have shown that untethered implants reduce the extent of the glial scar (Biran et al., 2007; Kim et al., 2004; Subbaroyan, 2007)
  • Parylene, polymide, and PDMS still each have moduli 6 orders of mangitude larger than that of the brain.
  • In some of their plots, immune response is higher around the nanocomposites!
    • Could be that their implant is still too large / stiff?
  • Note that recent research shows that vitemin may have neuroprotective effects --
    • Research has linked vimentin expression to rapid neurite extension in response to damage (Levin et al., 2009)
    • NG2+ cells that express vimentin have been proposed to support repair of central nervous system (CNS) damage, and stabilize axons in response to dieback from ED1+ cells (Alonso, 2005; Nishiyama, 2007; Busch et al., 2010)
  • Prior work (Frampton et al., 2010 PMID-20336824[2]) hypothesizes that a more compact GFAP response increases the impedance of an electrode which may decrease the quality of electrode recordings.

____References____

[0] Harris JP, Capadona JR, Miller RH, Healy BC, Shanmuganathan K, Rowan SJ, Weder C, Tyler DJ, Mechanically adaptive intracortical implants improve the proximity of neuronal cell bodies.J Neural Eng 8:6, 066011 (2011 Dec)
[1] Harris JP, Hess AE, Rowan SJ, Weder C, Zorman CA, Tyler DJ, Capadona JR, In vivo deployment of mechanically adaptive nanocomposites for intracortical microelectrodes.J Neural Eng 8:4, 046010 (2011 Aug)
[2] Frampton JP, Hynd MR, Shuler ML, Shain W, Effects of glial cells on electrode impedance recorded from neuralprosthetic devices in vitro.Ann Biomed Eng 38:3, 1031-47 (2010 Mar)

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ref: Lewitus-2011.08 tags: dissolving polymer electrodes histology degrading date: 01-25-2013 01:31 gmt revision:2 [1] [0] [head]

PMID-21609850[0] The fate of ultrafast degrading polymeric implants in the brain.

  • Tyrosene-derived terpolymer (protein?) dissolves within hours & was re-absorbed.
  • Second terpolymer degrades quickly but is not resorbed.
    • This type resulted in continuous glial activation and loss of neural tissue compared to first.
  • Makes sense, not unexpected.

____References____

[0] Lewitus DY, Smith KL, Shain W, Bolikal D, Kohn J, The fate of ultrafast degrading polymeric implants in the brain.Biomaterials 32:24, 5543-50 (2011 Aug)

{1205}
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ref: Rennaker-2005.03 tags: electrode recording longevity mechanical insertion Oklahoma MEA date: 01-25-2013 01:21 gmt revision:3 [2] [1] [0] [head]

PMID-15698656[0] A comparison of chronic multi-channel cortical implantation techniques: manual versus mechanical insertion.

  • Over 60% of the animals implanted with the mechanical insertion device had driven activity at week 6
    • whereas none of the animals with manually inserted arrays exhibited functional responses after 3 weeks.
      • Roughly identical responses immediately following surgery.
      • Could be that the manual inserter had horizontal movement / shear. (This is solveable with a stereotax).
      • Other research showed little difference in tissue response at 10um/s or 100um/s PMID-21896383[1]
  • Multi-wire electrodes.
  • Mechanical insertion device was capable of rapidly inserting the electrode without visible compression of the brain.
  • Response measured relative to auditory stimulus.
  • Their insertion device looks like a pen.

____References____

[0] Rennaker RL, Street S, Ruyle AM, Sloan AM, A comparison of chronic multi-channel cortical implantation techniques: manual versus mechanical insertion.J Neurosci Methods 142:2, 169-76 (2005 Mar 30)
[1] Welkenhuysen M, Andrei A, Ameye L, Eberle W, Nuttin B, Effect of insertion speed on tissue response and insertion mechanics of a chronically implanted silicon-based neural probe.IEEE Trans Biomed Eng 58:11, 3250-9 (2011 Nov)

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ref: Seymour-2009.1 tags: Parylene MEA biocompatibility pin hole water saturation PPX date: 01-25-2013 01:19 gmt revision:2 [1] [0] [head]

PMID-19703712[0] The insulation performance of reactive parylene films in implantable electronic devices.

  • Describe the development and testing of a superior form of parylene: poly(p-xylylene) functionalized with reactive group X (PPX-X)
  • Heat-treated PPX-X device impedance was 800% greater at 10kHz and 70% greater at 1Hz relative to heated parylene-C controls after 60 days (in saline).
  • Better wet attachment to the metal.

____References____

[0] Seymour JP, Elkasabi YM, Chen HY, Lahann J, Kipke DR, The insulation performance of reactive parylene films in implantable electronic devices.Biomaterials 30:31, 6158-67 (2009 Oct)

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ref: -0 tags: Shenoy eye position BMI performance monitoring date: 01-25-2013 00:41 gmt revision:1 [0] [head]

PMID-18303802 Cortical neural prosthesis performance improves when eye position is monitored.

  • This proposal stems from recent discoveries that the direction of gaze influences neural activity in several areas that are commonly targeted for electrode implantation in neural prosthetics.
  • Can estimate eye position directly from neural activity & subtract it when performing BMI predictions.

{1206}
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ref: -0 tags: flexible polymer electrode recording polypyrrole Bizzi date: 01-25-2013 00:39 gmt revision:0 [head]

PMID-19164034 Cortical recording with polypyrrole microwire electrodes.

  • http://web.mit.edu/bcs/bizzilab/publications/bae2008.pdf
  • Electropolymerization of PPy on a glassy carbon electrode in solution.
  • Polypyrrole microwires were prepared by mounting a PPy film perpendicular to the stage of a cryo-microtome and slicing it in 20um sections.
  • Electrode mounted inside a glass capillary tube.
  • Impedance: 1e5 @ 1kHz.

{1026}
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ref: Thelin-2011.01 tags: histology MEA tether tissue response malmo lund date: 01-24-2013 22:17 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-21298109[0] Implant size and fixation mode strongly influence tissue reactions in the CNS.

  • Overview: tethering and size both increase immune response, and causes continued GFAP activity.
    • An untethered 50um electrode exhibited very weak inflammatory response after 12 weeks.
      • Suggesting that a small electrode can move with the brain.
  • Tethering in their context means affixed rigidly to the bone.
    • Small-diameter, untethered implants cause the smallest tissue reactions.
    • Likely that this scales.
  • Stice et al 2007 {1111} -- GFAP expression was significantly smaller for 12 um diameter implants than 25um implants @ 4 weeks.
  • They used 50um and 200um stainless steel implants.
    • implants glued to micromanipulator using gelatine
  • 24 rats.
  • Much more GFAP and ED1 actviity in tethered implants; NEuN neural density about the same.
  • 50um implant had a higher NeuN + count.
  • Regarding implantation: not sure. Have to find a reference for stab wounds (where the inserter is retracted).

____References____

[0] Thelin J, Jörntell H, Psouni E, Garwicz M, Schouenborg J, Danielsen N, Linsmeier CE, Implant size and fixation mode strongly influence tissue reactions in the CNS.PLoS One 6:1, e16267 (2011 Jan 26)

{1202}
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ref: -0 tags: saccarose sugar sweet electrode implantation force germany date: 01-24-2013 21:46 gmt revision:0 [head]

PMID-22254391 Chronic intracortical implantation of saccharose-coated flexible shaft electrodes into the cortex of rats.

  • measured forces of about 6mN inserting the 75um diameter saccharose-coated electrode.
    • Individual wires were 40um in diameter.
  • Limited longitudinal histology or electrophysiology

{1111}
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ref: Stice-2007.06 tags: electrodes recording small rats S1 PGA histology GFAP date: 01-24-2013 21:07 gmt revision:9 [8] [7] [6] [5] [4] [3] [head]

PMID-17409479[0] Thin microelectrodes reduce GFAP expression in the implant site in rodent somatosensory cortex.

  • Implanted 12 um and 25 um polymide coated stainless steel
    • Wires coated with poly-glycolic acid (PGA) to facilitate implantation.
  • Only looked to 4 weeks.
  • 12 um implants significantly less GFAP (astrocyte) reactivity at 4 weeks, no difference at 2 weeks (figure 9 & 10).
    • B = bare, P = PGA coated.
  • Can use to bolster the idea that smaller implants are less irritating.

____References____

[0] Stice P, Gilletti A, Panitch A, Muthuswamy J, Thin microelectrodes reduce GFAP expression in the implant site in rodent somatosensory cortex.J Neural Eng 4:2, 42-53 (2007 Jun)

{737}
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ref: Biran-2005.09 tags: microelectrode Michigan probe glia tissue response electrode immune histology MEA Biran date: 01-24-2013 20:49 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-16045910[0] Neuronal cell loss accompanies the brain tissue response to chronically implanted silicon microelectrode arrays.

  • See also {1190} (wow, I'm redundant!)
  • Important point: ED1 up-regulation and neuronal loss were not observed in microelectrode stab controls, indicating that the phenotype did not result from the initial mechanical trauma of electrode implantation, but was associated with the foreign body response.
    • CD68 = ED1 is a marker for microglia and other macrophages. (wikipedia article is informative).
    • GFAP = glial fibrillary acidic protein, marker for astrocytes.
  • Recording failure is caused by chronic inflammation (mostly activated microglia) at the microelectrode brain tissue interface.
  • Only tested response 2 and 4 weeks after implantation. Makes sense for stab wound, but didn't the want to see a longer term response? Or do their electrodes just not last that long?
  • What did they coat the silicon probes in?
  • Used silastic to shock-mount their floating electrodes, but this apparently made no difference compared to conventional dental cement and bone screw mounting.
  • Suggest that chronic inflammatory response may be related to the absorption of fibrogen and complement to the surface of the device (device should not be porous?), the subsequent release of pro-inflammatory and cytotoxic cytokines by activated microphages, and the persistence of activated macrophages around materials which cannot be broken down.
    • Well then, how do you make the electrodes biochemically / biologically 'invisible'?
    • Persistently activated microglia are found around insoluble plaques in AD (plaques that cannot be / are not removed from the brain via proteolysis. Microglia form 'glitter cells' when they engulf undigestible stubstances). This has been termed 'frustrated phagocytosis', which results in increased secretion of proinflamatory cytokines that directly or indirectly cause neuronal death.
  • Significant reductions in neurofiliament reactivity was seen up to 230um from the microelectrode interface; this was not seen for stab wounds. Maximum recording distance is about 130um; 100um more reasonable in normal conditions.
  • Accumulating evidence from postmortem analysis of patients implanted with DBS electrodes reveals that chronic neuroinflamation is part of the response to such (duller, larger) implants as well. They have seen cell loss up to 1mm fromt the electrode surface here.

____References____

[0] Biran R, Martin DC, Tresco PA, Neuronal cell loss accompanies the brain tissue response to chronically implanted silicon microelectrode arrays.Exp Neurol 195:1, 115-26 (2005 Sep)

{749}
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ref: Biran-2007.07 tags: tresco biocompatibility tether skull electrodes Michigan probe recording Tresco date: 01-24-2013 20:11 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

PMID-17266019[0] The brain tissue response to implanted silicon microelectrode arrays is increased when the device is tethered to the skull.

  • Good, convincing, figures.

____References____

[0] Biran R, Martin DC, Tresco PA, The brain tissue response to implanted silicon microelectrode arrays is increased when the device is tethered to the skull.J Biomed Mater Res A 82:1, 169-78 (2007 Jul)

{1199}
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ref: -0 tags: histology atryocytes immune response electrode arrays lund multiple exacerbate date: 01-24-2013 19:56 gmt revision:1 [0] [head]

PMID-23091629 Multiple implants do not aggravate the tissue reaction in rat brain.

  • After six weeks, the astrocytic scar surrounding the middle out of five implants was significantly smaller compared to the single contralateral implant, suggesting that an intrahemispheric interaction might be taking place, reducing the astrocytic response around the central implant.
  • Weak (?) staining for ED1 in this study?
  • -- after 6 weeks.
  • Thought: every paper has a different method for quantify immune response, GFAP staining in this case.

{1024}
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ref: COLLIAS-1957.05 tags: histology microelectrode vasulature date: 01-23-2013 23:56 gmt revision:4 [3] [2] [1] [0] [head]

PMID-13429398[0] Histopathological changes produced by implanted electrodes in cat brains; comparison with histopathological changes in human and experimental puncture wounds.

  • Quite a good and overcomplete / long article -- fully describes their result of implanting bundles of 0.005" varnished steel wires into the brains of cats.
    • Saw hemorrhagic necrosis, necrosis from edema, and eventual encapsulation and collapse of capilaries around the chronic implant. All things that we still have to contend with.
  • From [1]: ... For single penetrating electrodes into cat cortex, Collias and Manuelidis noted and increase in hemorrhagic damage near electrode tracks of the cortex nearest the point of electrode entry into the pia.
  • They also reported that the damage appeared to be randomly distributed among the implants, which they attributed to differences in local vasculature.
  • The toxicity of certain metals, namely, platinum, platinum-8% tungsten, platinum-10% rhodium, platinum-10% iridium, platinum-10% nickel, platinized platinum, a gold-nickel-chromium alloy, a gold-palladium-rhodium alloy, a chromium-nickel-molybdenum alloy (Vitallium), stainless steel, silver, rhenium, and gold, was evaluated histologically following chronic implantation for 2 months in the brains of cats. Of the above metals, all but silver were found to be nontoxic. Boron was also evaluated and found to be nontoxic.

____References____

[0] COLLIAS JC, MANUELIDIS EE, Histopathological changes produced by implanted electrodes in cat brains; comparison with histopathological changes in human and experimental puncture wounds.J Neurosurg 14:3, 302-28 (1957 May)
[1] Rousche PJ, Normann RA, Chronic recording capability of the Utah Intracortical Electrode Array in cat sensory cortex.J Neurosci Methods 82:1, 1-15 (1998 Jul 1)

{1194}
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ref: Narayanan-2005.04 tags: BMI reliability noise Laubach Yale synergy date: 01-23-2013 20:50 gmt revision:1 [0] [head]

PMID-15858046[0] Redundancy and synergy of neuronal ensembles in motor cortex.

  • Reaction time task.
  • Neurons that were the best individual predictors of task performance were not necessarily the neurons that contributed the most predictive information to an ensemble of neurons.
  • Small ensembles [of neurons] could exhibit synergistic interactions (e.g., 23 +/- 9% of ensembles with two neurons were synergistic).
  • In contrast, larger ensembles exhibited mostly redundant interactions (e.g., 99 +/- 0.1% of ensembles with eight neurons were redundant).
  • Possible interpretation: redundancy enables robustness.

____References____

[0] Narayanan NS, Kimchi EY, Laubach M, Redundancy and synergy of neuronal ensembles in motor cortex.J Neurosci 25:17, 4207-16 (2005 Apr 27)

{913}
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ref: Ganguly-2011.05 tags: Carmena 2011 reversible cortical networks learning indirect BMI date: 01-23-2013 18:54 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

PMID-21499255[0] Reversible large-scale modification of cortical networks during neuroprosthetic control.

  • Split the group of recorded motor neurons into direct (decoded and controls the BMI) and indirect (passive) neurons.
  • Both groups showed changes in neuronal tuning / PD.
    • More PD. Is there no better metric?
  • Monkeys performed manual control before (MC1) and after (MC2) BMI training.
    • The majority of neurons reverted back to original tuning after BC; c.f. [1]
  • Monkeys were trained to rapidly switch between manual and brain control; still showed substantial changes in PD.
  • 'Near' (on same electrode as direct neurons) and 'far' neurons (different electrode) showed similar changes in PD.
    • Modulation Depth in indirect neurons was less in BC than manual control.
  • Prove (pretty well) that motor cortex neuronal spiking can be dissociated from movement.
  • Indirect neurons showed decreased modulation depth (MD) -> perhaps this is to decrease interference with direct neurons.
  • Quote "Studies of operant conditioning of single neurons found that conconditioned adjacent neurons were largely correlated with the conditioned neurons".
    • Well, also: Fetz and Baker showed that you can condition neurons recorded on the same electrode to covary or inversely vary.
  • Contrast with studies of motor learning in different force fields, where there is a dramatic memory trace.
    • Possibly this is from proprioception activating the cerebellum?

Other notes:

  • Scale bars on the waveforms are incorrect for figure 1.
  • Same monkeys as [2]

____References____

[0] Ganguly K, Dimitrov DF, Wallis JD, Carmena JM, Reversible large-scale modification of cortical networks during neuroprosthetic control.Nat Neurosci 14:5, 662-7 (2011 May)
[1] Gandolfo F, Li C, Benda BJ, Schioppa CP, Bizzi E, Cortical correlates of learning in monkeys adapting to a new dynamical environment.Proc Natl Acad Sci U S A 97:5, 2259-63 (2000 Feb 29)
[2] Ganguly K, Carmena JM, Emergence of a stable cortical map for neuroprosthetic control.PLoS Biol 7:7, e1000153 (2009 Jul)

{270}
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ref: Hochberg-2006.07 tags: BMI Donoghue Utah probe Nature tetraplegia Hochberg 2006 date: 01-23-2013 18:49 gmt revision:4 [3] [2] [1] [0] [head]

PMID-16838014[] Neuronal ensemble control of prosthetic devices by a human with tetraplegia

  • patient was able to talk?
  • 96-channel microelectrode array implanted in arm/hand knob or right precentral gyrus.
  • around 30 units / day observed.
  • 90% of units showed significantly varied firing rates (K-S test) during imagined movements.
  • 2D control. Good pursuit tracking and center-out performance.
  • Used Wiener filter.
  • also see the technology review

____References____

{142}
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ref: Schalk-2000.12 tags: error potential EEG wadsworth BCI 2000 BMI date: 01-23-2013 07:15 gmt revision:3 [2] [1] [0] [head]

PMID-11090763[0] EEG-based communication: presence of an error potential.

  • Idea: they trained a set of subjects to use mu/beta rhythm over central sulcus (sensorimotor) amplitude to move a cursor around the screen, and simultaneously monitored for error-related potentials to correct errors in decoding.
  • patients get 80-97% accuracy in a binary choice task.
  • look at the end of a trial to see if they 'approve' of the choice.
  • had to remove eyeblink artifacts! however, people tend to defer eyeblinks until the end of performance.
  • error = average EEG during error trials - EEG during correct trial. (a potential)
    • the error was over primary motor/ somatosensory cortex.
    • used adaptive noise cancellation to remove some of the eyeblink EMG.

____References____

[0] Schalk G, Wolpaw JR, McFarland DJ, Pfurtscheller G, EEG-based communication: presence of an error potential.Clin Neurophysiol 111:12, 2138-44 (2000 Dec)

{1052}
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ref: Chestek-2009.09 tags: BMI problems address critique spike sorting Shenoy date: 01-23-2013 02:23 gmt revision:3 [2] [1] [0] [head]

IEEE-5332822 (pdf) Neural prosthetic systems: Current problems and future directions

  • Where there is unlikely to be improvements: spike sorting and spiking models.
  • Where there are likely to be dramatic improvements: non-stationarity of recorded waveforms, limitations of a linear mappings between neural activity and movement kinematics, and the low signal to noise ratio of the neural data.
  • Compare different sorting methods: threshold, single unit, multiunit, relative to decoding.
  • Plot waveform changes over an hour -- this contrasts with earlier work (?) {1032}
  • Figure 5: there is no obvious linear transform between neural activity and the kinematic parameters.
  • Suggest that linear models need to be replaced by the literature of how primates actually make reaches.
  • Discuss that offline performance is not at all the same as online; in the latter the user can learn and adapt on the fly!

____References____

Chestek, C.A. and Cunningham, J.P. and Gilja, V. and Nuyujukian, P. and Ryu, S.I. and Shenoy, K.V. Engineering in Medicine and Biology Society, 2009. EMBC 2009. Annual International Conference of the IEEE 3369 -3375 (2009)

{1192}
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ref: -2002 tags: sea slugs flexible electrodes polymide Washington date: 01-04-2013 18:46 gmt revision:0 [head]

IEEE-1002325 (pdf) Silicon micro-needles with flexible interconnections

  • Implanted their isolated needles (see also {219}) in sea slugs Tritonia diomedea
    • Sea slug neurons are large -- up to 400um -- makes recording easier.
  • Silicon needles fabricated via reactive ion etching and SF6 sharpening.
  • 'intracellular recording!
  • Pretty advanced fabrication, I guess.

{1040}
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ref: Du-2011.01 tags: Harrison recording electrode MEA Blanche date: 01-04-2013 02:43 gmt revision:3 [2] [1] [0] [head]

PMID-22022568[0] Multiplexed, High Density Electrophysiology with Nanofabricated Neural Probes

  • The number of single-units possible to record doubles every 7 years [5].
  • Electrodes must be within 100um of soma to relaibly detect extracellular action potentials.
  • Existing Michigan arrays have trace features around >=1 um; here they use E-beam lithography to decrease the probe width dramatically.
    • Their wire widths are 290 nm. Still bigger than 40nm process (?)
  • Seem to use Reid Harrison's ASIC RHA22132 design.
  • noise of electrodes progressively decreased with consecutive gold electroplating cycles. Plating makes the electrodes rough, and decreases their impedance to around 1 M.
    • Electrode contacts are around 10 x 10 um square, 108 um^2 area.
  • Intrinsic noise of the amplifier 1.7 uV RMS.
  • 290 nm wire had an impedance of 9.2 k -- corresponding to 1.0 uV rms noise.
  • able to record from the same neuron from several adjacent electrodes. Spacing ~ 28 um.
  • Detail their process extensively -- 40% of probes survived the process with <= 5 defective channels. THey propose further optimization to the e-beam lithography. Probes took 7 hours to pattern on the lithography machine (!).

____References____

[0] Du J, Blanche TJ, Harrison RR, Lester HA, Masmanidis SC, Multiplexed, high density electrophysiology with nanofabricated neural probes.PLoS One 6:10, e26204 (2011)

{1102}
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ref: Gilletti-2006.09 tags: electrode micromotion histology GFAP variable reluctance date: 01-04-2013 02:28 gmt revision:2 [1] [0] [head]

PMID-16921202[0] Brain micromotion around implants in the rodent somatosensory cortex.

  • Used a differential variable reluctance transducer (DVRT) in adult rats (n = 6) to monitor micromotion normal to the somatosensory cortex surface
    • Reluctance e.g. AC inductance varied with a floating bobbin (or so -- they do not list the details of this COTS device).
  • Pulsatile surface micromotion was observed to be in the order of 10-30 um due to pressure changes during respiration and 2-4 um due to vascular pulsatility.
  • Large inward displacements of brain tissue between 10-60 um were observed in n = 3 animals immediately following the administration of anesthesia

____References____

[0] Gilletti A, Muthuswamy J, Brain micromotion around implants in the rodent somatosensory cortex.J Neural Eng 3:3, 189-95 (2006 Sep)

{1190}
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ref: Biran-2005.09 tags: Tresco histology chronic implantation astrocytes microglia date: 01-04-2013 02:28 gmt revision:3 [2] [1] [0] [head]

PMID-16045910[0] Neuronal cell loss accompanies the brain tissue response to chronically implanted silicon microelectrode arrays.

  • We observed persistent ED1 immunoreactivity around implanted silicon microelectrode arrays implanted in adult rat cortex that was accompanied by a significant reduction in nerve fiber density and nerve cell bodies in the tissue immediately surrounding the implanted silicon microelectrode arrays.
  • We found that explanted electrodes were covered with ED1/MAC-1 immunoreactive cells and that the cells released MCP-1 and TNF-a under serum-free conditions in vitro.
  • See also [1] and [2]
  • Electrodes: Michigan type, 5mm long, 200um wide tapering to 30um, 15um thick at the shank tapering to 2um.
    • Show that the chronic response is markedly different than acute stab wounds.
    • "Stab wounds resulted in comparatively minimal neurofilament loss at 2 weeks (A) and no apparent loss by 4 weeks".
    • "The number of neuronal bodies is reduced in the area adjacent to microelectrodes (B, D) but appears unaltered surrounding stab wound lesions (A, C; lesion site in center of each image)."
  • Includes details of immunostaining, which could be useful.

____References____

[0] Biran R, Martin DC, Tresco PA, Neuronal cell loss accompanies the brain tissue response to chronically implanted silicon microelectrode arrays.Exp Neurol 195:1, 115-26 (2005 Sep)
[1] Szarowski DH, Andersen MD, Retterer S, Spence AJ, Isaacson M, Craighead HG, Turner JN, Shain W, Brain responses to micro-machined silicon devices.Brain Res 983:1-2, 23-35 (2003 Sep 5)
[2] Gilletti A, Muthuswamy J, Brain micromotion around implants in the rodent somatosensory cortex.J Neural Eng 3:3, 189-95 (2006 Sep)

{1058}
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ref: -0 tags: Purdue magnetic bullet electrode implantation date: 01-04-2013 00:51 gmt revision:3 [2] [1] [0] [head]

PMID-19596378 Magnetic insertion system for flexible electrode implantation.

  • Probes constructed from a sharp magnetic tip attached to a flexible tether.
  • Cite Polikov et al 2005. {781}.
  • Re micromotion: (Gilletti and Muthuswamy, 2006 {1102}; Lee et al., 2004; Subbaroyan et al., 2005 {1103}).
  • 0.6 mm (600 um!) diameter steel bullet, 4mm long, on the end of 38 gauge magnet wire. Mass 7.2 +- 0.4 mg.
  • Peak current 520 A froman 800V, 900uF capacitor which produces a maximum force of 10 N on the electrode, driving it at 126.25 m/s.
  • Did manage to get neural data.
  • Experimental evidence suggests that macrophages have difficulty adhering to and spreading on polymer fibers ranging between 2.1 and 5.9 um in diameter. PMID-8902241 Bernatchez et al. 1996 and {746}.
  • Shot through the dura.
  • Also reference magnetic stereotaxis for use in manipulating magnetic 'seeds' through cancers for hyperthremic destruction.
  • See also their 2011 AES abstract

{1189}
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ref: -0 tags: microelectrode array flexible PDMS via interconnect Georgia date: 01-04-2013 00:33 gmt revision:0 [head]

IEEE-6197244 (pdf) A PDMS-Based Integrated Stretchable Microelectrode Array (isMEA) for Neural and Muscular Surface Interfacing

  • Targeted at e.g. ECoG; in this paper, they look at cat muscle (epimyscial recording).
  • MEA is directly fabricated with a stretchable substrate, such as a thin PCB or ASIC, through via bonding for built-in packaging.

{1188}
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ref: -0 tags: flexible micxrowire arrays electrode recording Georgia polymide date: 01-04-2013 00:13 gmt revision:1 [0] [head]

IEEE-906517 (pdf) Flexible microelectrode arrays with integrated insertion devices

  • 2001 MEMS Conference.
  • FMA = flexible microelectrode arrays.
  • Both for nerves (pass-through needle) and cortex (removeable needle).
    • Primarily tested in tissue proxies.
  • Anticipated the utility of photolithography for patterning the electrodes + rigid insertion devices.
  • The elastic modulus of polymers like polymide are two orders of magnitude less than metals, but still six orders of magnitude higher than brain tissue (46kPa).
  • Pass-through needle very similar to the threaded wire idea.
  • removable needle simply stops the thread & drives the needle a bit further to break the attachment site.
    • Did not test removable needle technique (?)
  • Defined electroplating with a thick photoresist mask, as Michel says.
  • Tested FMAs with movement and acceleration vs. rigid arrays. FMAs faired much better, of course!

____References____

' ''' ()

{1178}
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ref: -0 tags: parylene flexible neural recording drug delivery microfluidics 2012 inserter needle release date: 01-02-2013 22:41 gmt revision:1 [0] [head]

PMID-23160191 Novel flexible Parylene neural probe with 3D sheath structure for enhancing tissue integration

  • They seem to think that drugs are critical for success: "These features will enhance tissue integration and improve recording quality towards realizing reliable chronic neural interfaces."
  • Similar to Kennedy: "The sheath structure allows for ingrowth of neural processes leading to improved tissue/probe integration post implantation." 8 electrodes, 4 on the cone interior, 4 on the exterior.
    • opening is 50um at tip, 300 um at base.
  • Used a PEEK-stiffened parylene ZIF connection.
  • Only tested in agarose, but it did properly release from the inserter needle.
  • I wonder if we could use a similar technique..
  • "Lab on a chip" journal (Royal society of Chemistry). nice.

{1187}
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ref: -0 tags: neural recording topologies circuits operational transconductance amplifiers date: 01-02-2013 20:00 gmt revision:0 [head]

PMID-22163863 Recent advances in neural recording microsystems.

  • Decent review. Has some depth on the critical first step of amplification.

{1186}
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ref: -0 tags: voltage sensitive dyes fluorescent protein date: 01-02-2013 05:08 gmt revision:0 [head]

PMID-20622860 Imaging brain electric signals with genetically targeted voltage-sensitive fluorescent proteins.

  • Interesting: Most fluorescent fusion proteins form intracellular aggregates during long-term expression in mammalian neurons, although this effect appears to be minimal in Aequorea victoria–derived fluorescent proteins.
  • See also {1185}

{1184}
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ref: -0 tags: optical neural recording photon induced electron transfer date: 01-02-2013 04:25 gmt revision:2 [1] [0] [head]

PMID-22308458 Optically monitoring voltage in neurons by photo-induced electron transfer through molecular wires.

  • Photoinduced electron transfer.
    • About what you would think -- a photon bumps an electron into a higher orbital, and this electron can be donated to another group or drop back down & fluoresce a photon.
  • Good sensitivity: ΔF/F of 20-27% per 100mV, fast kinetics.
  • Not presently genetically targetable.
  • Makes sense in terms of energy: "A 100-mV depolarization changes the PeT driving force by 0.05 eV (one electron × half of 100-mV potential, or 0.05 V). Because PeT is a thermally controlled process, the value of 0.05 eV is large relative to the value of kT at 300 K (0.026 eV), yielding a large dynamic range between the rates of PeT at resting and depolarized potentials.
  • Why electrochromic dyes have plateaued:
    • "In contrast, electrochromic dyes have smaller delta G values, 0.003 (46) to 0.02 (47) eV, and larger comparison energies. Because the interaction is a photochemically controlled process, the energy of the exciting photon is the comparison energy, which is 1.5–2 eV for dyes in the blue-to-green region of the spectrum. Therefore, PeT and FRET dyes have large changes in energy versus their comparison energy (0.05 eV vs. 0.026 eV), giving high sensitivities; electrochromic dyes have small changes compared with the excitation photon (0.003–0.02 eV vs. 2 eV), producing low voltage sensitivity."

{1183}
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ref: -0 tags: optical imaging neural recording diamond magnetic date: 01-02-2013 03:44 gmt revision:0 [head]

PMID-22574249 High spatial and temporal resolution wide-field imaging of neuron activity using quantum NV-diamond.

  • yikes: In this work we consider a fundamentally new form of wide-field imaging for neuronal networks based on the nanoscale magnetic field sensing properties of optically active spins in a diamond substrate.
  • Cultured neurons.
  • NV = nitrogen-vacancy defect centers.
    • "The NV centre is a remarkable optical defect in diamond which allows discrimination of its magnetic sublevels through its fluorescence under illumination. "
    • We show that the NV detection system is able to non-invasively capture the transmembrane potential activity in a series of near real-time images, with spatial resolution at the level of the individual neural compartments.
  • Did not actually perform neural measurements -- used a 10um microwire with mA of current running through it.
    • I would imagine that actual neurons have far less current!

{1182}
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ref: -0 tags: optical recording voltage sensitive dyes redshirt date: 01-02-2013 03:17 gmt revision:3 [2] [1] [0] [head]

PMID-16050036 Imaging brain activity with voltage- and calcium-sensitive dyes.

  • Voltage-sensitive dyes are well suited for measuring synaptic integration, as:
    • Electrodes are too blunt to effectively record these fine, < 1um diameter structures.
    • The surface area to volume ratio is highest in the dendrites
    • Voltage-sensitive dyes also permeate internal membranes not subject to voltage gradients, hence this does not contribute to the signal, leading to a decreased ΔF/F .
  • Dominant experimental noise is shot noise, statistical -- see {1181}.
  • modern dyes and imagers can reliably record single action potentials; spatial averaging yields similar resolution as electrical recording.
  • They performed optical recording of Aplysia sensory ganglia, and discovered following light tail touch: "It is almost as if the Aplysia nervous system is designed such that every cell in the abdominal ganglion cares about this (and perhaps every) sensory stimulus. In addition, more than 1000 neurons in other ganglia are activated by this touch..."
      • These results force a more pessimistic view of the present understanding of the neuronal basis of apparently simple behaviors in relatively simple nervous systems.
  • Used calcium imaging on olfactory glomeruli of mice and turtles; measurements were limited by either shot-noise or heart/breathing artifacts.
  • Confocal and two-photon microscopes, due to their exchange of spatial resolution for sensitivity, are not useful with voltage-sensitive dyes.
    • The generation of fluorescent photons in the 2-photon confocal microscope is not efficient. We compared the signals from Calcium Green-1 in the mouse olfactory bulb using 2-photon and ordinary microscopy. In this comparison the number of photons contributing to the intensity measurement in the 2-photon confocal microscope was about 1000 times smaller than the number measured with the conventional microscope and a CCD camera.
  • By the numbers, quote: Because only a small fraction of the 10e16 photons/ms emitted by a tungsten filament source will be measured, a signal-to-noise ratio of 10e8 (see above) cannot be achieved. A partial listing of the light losses follows. A 0.9-NA lamp collector lens would collect 0.1 of the light emitted by the source. Only 0.2 of that light is in the visible wavelength range; the remainder is infrared (heat). Limiting the incident wavelengths to those, which have the signal means, that only 0.1 of the visible light is used. Thus, the light reaching the
preparation might typically be reduced to 1013 photons/ms. If the light-collecting system that forms the image has high efficiency e.g., in an absorption measurement, about 1013 photons/ms will reach the image plane. (In a fluorescence measurement there will be much less light measured because 1. only a fraction of the incident photons are absorbed by the fluorophores, 2. only a fraction of the absorbed photons appear as emitted photons, and 3. only a fraction of the emitted photons are collected by the objective.) If the camera has a quantum efficiency of 1.0, then, in absorption, a total of 10e13 photoelectrons/ms will be measured. With a camera of 1000 pixels, there will be 10e10 photoelectrons/ms/pixel. The shot noise will be 10e5 photoelectrons/ms/pixel; thus the very best that can be expected is a noise that is 10e−5 of the resting light (a signal-to-noise ratio of 100 db). The extra light losses in a fluorescence measurement will further reduce the maximum obtainable signal-to-noise ratio.

{1181}
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ref: -0 tags: neural imaging recording shot noise redshirt date: 01-02-2013 02:20 gmt revision:0 [head]

http://www.redshirtimaging.com/redshirt_neuro/neuro_lib_2.htm

  • Shot Noise: The limit of accuracy with which light can be measured is set by the shot noise arising from the statistical nature of photon emission and detection.
    • If an ideal light source emits an average of N photons/ms, the RMS deviation in the number emitted is N .
    • At high intensities this ratio NN is large and thus small changes in intensity can be detected. For example, at 10^10 photons/ms a fractional intensity change of 0.1% can be measured with a signal-to-noise ratio of 100.
    • On the other hand, at low intensities this ratio of intensity divided by noise is small and only large signals can be detected. For example, at 10^4 photons/msec the same fractional change of 0.1% can be measured with a signal-to-noise ratio of 1 only after averaging 100 trials.

{1179}
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ref: -0 tags: optical coherence tomography neural recording squid voltage sensitive dyes review date: 12-23-2012 21:00 gmt revision:4 [3] [2] [1] [0] [head]

PMID-20844600 Detection of Neural Action Potentials Using Optical Coherence Tomography: Intensity and Phase Measurements with and without Dyes.

  • Optical methods of recording have been investigated since the 1940's:
    • During action potential (AP) propagation in neural tissue light scattering, absorption, birefringence, fluorescence, and volume changes have been reported (Cohen, 1973).
  • OCT is reflection-based, not transmission: illuminate and measure from the same side.
    • Here they use spectral domain OCT, where the mirror is not scanned; rather SD-OCT uses a spectrometer to record interference of back-scattered light from all depth points simultaneously (Fercher et al., 1995).
    • Use of a spectrometer allows imaging of an axial line within 10-50us, sufficient for imaging action potentials.
    • SD-OCT, due to some underlying mathematics which I can't quite grok atm, can resolve/annul common-mode phase noise for high temporal and Δphase measurement (high sensitivity).
      • This equates to "microsecond temporal resolution and sub-nanometer optical path length resolution".
  • OCT is generally (intially?) used for in-vivo imaging of retinas, in humans and other animals.
  • They present new data for depth-localization of neural activity in squid giant axons (SGA) stained with a voltage-sensitive near-infrared dye.
    • Note: averaged over 250 sweeps.
  • ΔPhase>>ΔIntensity -- figure 4 in the paper.
  • Use of voltage-sensitive dyes improves the resolution of ΔI , but not dramatically --
    • And Δphase is still a bit delayed.
    • Electrical recording is the control.
      • It will take significant technology development before optical methods exceed electrical methods...
  • Looks pretty preliminary. However, OCT can image 1-2mm deep in transparent tissue, which is exceptional.
  • Will have to read their explanation of OCT.
  • Used in a squid giant axon prep. 2010, wonder if anything new has been done (in vivo?).
  • Claim that progress is hampered by limited understanding of how these Δphase signals arise.

{1180}
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ref: -0 tags: optical coherence tomography neural recording aplysia date: 12-23-2012 09:12 gmt revision:2 [1] [0] [head]

PMID-19654752 Detecting intrinsic scattering changes correlated to neuron action potentials using optical coherence imaging.

  • Aplysia, intrinsic imaging of scattering change following electrical stimulation.
    • Why did it take so long for them to get this paper out.. ?
  • Nicolelis first cited author.
  • Quality of recording not necessarily high.
  • quote: "Typical transverse resolutions in OCT (10-20um) are likely insufficient to identify smaller mamallian neurons that are often studied in neuroscience."
    • Solution: optical coherence microscopy (OCM), where a higher NA lens focuses the light to a smaller spot.
    • Expense: shorter depth-of-field.
  • Why does this work? "One mechanism of these optical signals is believed to be a realignment of charged membrane proteins in response to voltage change [6].
  • A delay of roughly 70ms was observed between the change in membrane voltage and the change in scattering intensity.
    • That's slow! Might be due to conduction velocity in Aplysia.
  • SNR of scattering measurement not too high -- the neurons are alive, afterall, and their normal biological processes cause scattering changes.
    • Killing the neurons with KCl dramatically decreased the variance of scattering, consistent with this hpothesis.
  • Birefringence: "Changes in the birefringence of nerves due to electrical activity have been shown to be an order of magnitude larger than scattering intensity changes" PMID-5649693

{1175}
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ref: -0 tags: flexible polymer neural probes compliant MIT EPFL 2008 date: 12-22-2012 01:28 gmt revision:0 [head]

Demonstration of cortical recording using novel flexible polymer neural probes

  • Two layer platinum process minimizes probe size -- nice. Might be useful for our purposes.
  • used electrochemical etching to release the lithographically patterned devices from the sacrificial aluminum layer.
  • Impedance looks pretty high -- 500k at 1kHz.
  • They talk about PCA as though it's unusual to them (?)
  • Histology uncontrolled and un-quantitiative.

{1174}
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ref: -0 tags: Hinton google tech talk dropout deep neural networks Boltzmann date: 11-09-2012 18:01 gmt revision:0 [head]

http://www.youtube.com/watch?v=DleXA5ADG78

  • Hinton believes in the the power of crowds -- he thinks that the brain fits many, many different models to the data, then selects afterward.
    • Random forests, as used in predator, is an example of this: they average many simple to fit and simple to run decision trees. (is apparently what Kinect does)
  • Talk focuses on dropout, a clever new form of model averaging where only half of the units in the hidden layers are trained for a given example.
    • He is inspired by biological evolution, where sexual reproduction often spontaneously adds or removes genes, hence individual genes or small linked genes must be self-sufficient. This equates to a 'rugged individualism' of units.
    • Likewise, dropout forces neurons to be robust to the loss of co-workers.
    • This is also great for parallelization: each unit or sub-network can be trained independently, on it's own core, with little need for communication! Later, the units can be combined via genetic algorithms then re-trained.
  • Hinton then observes that sending a real value p (output of logistic function) with probability 0.5 is the same as sending 0.5 with probability p. Hence, it makes sense to try pure binary neurons, like biological neurons in the brain.
    • Indeed, if you replace the backpropagation with single bit propagation, the resulting neural network is trained more slowly and needs to be bigger, but it generalizes better.
    • Neurons (allegedly) do something very similar to this by poisson spiking. Hinton claims this is the right thing to do (rather than sending real numbers via precise spike timing) if you want to robustly fit models to data.
      • Sending stochastic spikes is a very good way to average over the large number of models fit to incoming data.
      • Yes but this really explains little in neuroscience...
  • Paper referred to in intro: Livnat, Papadimitriou and Feldman, PMID-19073912 and later by the same authors PMID-20080594

{1173}
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ref: -0 tags: Moshe looks automatic programming google tech talk links date: 11-07-2012 07:38 gmt revision:3 [2] [1] [0] [head]

List of links from Moshe Looks google tech talk:

{1171}
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ref: -0 tags: Zador Peikon cold spring plos date: 11-06-2012 19:46 gmt revision:1 [0] [head]

Sequencing the Connectome

  • Quote: "Interestingly, the utility of the connectome in C. elegans is somewhat limited because function is highly multiplexed, with different neurons performing different roles depending on the state of neuromodulation [7], possibly as a mechanism for compensating for the small number of neurons."
  • In comparison, the authors argue that the role of neurons in mammalian brains is much more highly determined by connectivity / physical location, and support this with examples from the visual system (area MT; how layer in V1 determines simple vs. complex tuning).
  • Only have started work on this highly ambitious project -- current plan is to use PRV amplicons for permuting the neuronal barcodes -- and offer no results, just the general framework of the idea.
    • Given that Ian spoke of the idea when he first started at CSH, I wonder just how practical this idea is?

{1170}
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ref: -0 tags: git notes date: 08-22-2012 22:28 gmt revision:3 [2] [1] [0] [head]

This from: http://www.youtube.com/watch?v=ZDR433b0HJY also: http://gitref.org/

Useful commands.

git config --global user.name "Tim Hanson"
git config --global user.email "err@gmail.com"
git config --global color.ui true
git clone https://github.com/tlh24/sabes-exp-ctrl.git
	Clone our experimental control repository. 
	Piggbacks on ssh. 
git status
	Review changed files. 
git commit -am "message" 
	Add all changed files to the local database 
	basically the same as svn ci
git checkout -b 'label1' 'label2'
	Creates a new branch called 'label1' from the branch 'label2'
git push origin 'label'
	Push local commits to origin (in htis case github) for the master branch. 
	Does *not* do merging. 
git merge 'label'
	merge the present branch with branch 'label'
	You can merge multiple times, efficiently -- perfect for different lab setups. 

Full list:

git init
	or
git clone https://github.com/tlh24/sabes-exp-ctrl.git
	Clone our experimental control repository. 
	Piggbacks on ssh. 
	
git add .
	Stages changes for all files in the current directory.
git add -p
	Add files in sections -- in case you don't want to add all changes in a file.
git add <resolved file>
	Commit changes / conflict resolved file (after a merge)
	
git status
	Review changed files. 
	
git commit -m "message"
	(commits changes to local database)
git commit -am "message" 
	Add all changed files to the local database 
	basically the same as svn ci
	
git log
	Examine the current branch's log
git log --oneline 'label'
	Simplified log for branch 'label'. 
git log master ^origin/master
	Show the changes that are in local master branch, but not in origin master.
	This is equivalent to outgoing changes not yet pushed.
git log origin/master ^master
	Show the changes in origin/master, but not in the local master. 
	This is equivalent to 'incoming'. 
	
git branch
	List the available branches
git branch 'label'
	Make a new branch!
	Since branches are nothing but pointers to commits, this is a cheap operation. 
	Branching is a good way of saving state; it's easy to revert to one once labeled.
	
git checkout -b 'label'
	switches to branch 'label'
git checkout -b 'label1' 'label2'
	Creates a new branch called 'label1' from the branch 'label2'
	
git merge 'label'
	merge the present branch with branch 'label'
	You can merge multiple times, efficiently -- perfect for different lab setups. 
git merge --ff-only master
	Particuarly, can use to merge from master into particular setups!
		Much better than subversion.
git mergetool 
	Open a visual merging tool (kdiff3, etc -- same format as subversion)

git diff
	Shows changed files relative to local DB. 
	All comparisons are on local data, so are fast!


git push origin master
	Push local commits to origin (in htis case github) for the master branch. 
	Does *not* do merging. 
	If you do need to merge changes:
git fetch 
	Pull down *all* changes from the origin. 
git merge origin/master
	Merge current branch with that from the server.
git pull
	Pull the current branch from the origin, and automatically try to locally merge.
	ujst a shortcut for git fetch and merge; better not to use unless you're allways on master.
	"If you do a pull in a branch that is not tracked you're totally screwed."
git remote add <label> <url>
	Add a remote repository, which you can hten fetch (and merge) from. 
	Opposite direction from subversion -- the mantainers pull from trusted sources, 
	rather than developers pushing to a central repository. 
	This is sort-of how the linux kernel does it. 

{1169}
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ref: -0 tags: artificial intelligence projection episodic memory reinforcement learning date: 08-15-2012 19:16 gmt revision:0 [head]

Projective simulation for artificial intelligence

  • Agent learns based on memory 'clips' which are combined using some pseudo-bayesian method to trigger actions.
    • These clips are learned from experience / observation.
    • Quote: "..more complex behavior seems to arise when an agent is able to “think for a while” before it “decides what to do next.” This means the agent somehow evaluates a given situation in the light of previous experience, whereby the type of evaluation is different from the execution of a simple reflex circuit"
    • Quote: "Learning is achieved by evaluating past experience, for example by simple reinforcement learning".
  • The forward exploration of learned action-stimulus patterns is seemingly a general problem-solving strategy (my generalization).
  • Pretty simple task:
    • Robot can only move left / right; shows a symbol to indicate which way it (might?) be going.

{1155}
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ref: -0 tags: filtering spike sorting AUC ROC r date: 08-08-2012 23:35 gmt revision:12 [11] [10] [9] [8] [7] [6] [head]

A frequent task in the lab is to sort spikes (extracellular neural action potentials) from background noise. In the lab we are working on doing this wirelessly; to minimize power consumption, spike sorting is done before the radio. In this way only times of spikes need be transmitted, saving bandwidth and power. (This necessitates a bidirectional radio protocol, but this is a worthy sacrifice).

In most sorting programs (e.g. Plexon), the raw signal is first thresholded, then waveform snippets (typically 32 samples long) are compared to a template to accept/reject them, or to sort them into different units. The comparison metric is usually the mean-squared error, MSE, aka the L2 norm. This makes sense, as the spike shapes are assumed to be stereotyped (they may very well not be), and the noise white / uncorrelated (another debatable assumption).

On the headstage we are working with for wireless neural recording, jumps and memory moves are expensive operations, hence we've elected to do no waveform extraction, and instead match continuously match. By using the built-in MPEG compression opcodes, we can compute the L1 norm at a rate of 4 samples / clock -- very efficient. However, this was more motivated by hardware considerations an not actual spike sorting practice. Literature suggests that for isolating a fixed-pattern signal embedded in noise, the best solution is instead a matched filter.

Hence, a careful study of spike-sorting was attempted in matlab, given the following assumptions: fixed spike shape (this was extracted from real data), and uncorrelated band-limited noise. The later was just white noise passed through a bandpass filter, e.g.

cheby1(3, 2, [500/15e3 7.5/15])

Where the passband edges are 500 Hz and 15kHz, at a sampling rate of 30kHz. (Actual rate is 31.25kHz). Since the spike times are known, we can rigorously compare the Receiver Operating Characteristic (ROC) and the area under curve (AUC) for different sorting algorithms. Four were tried: L1 (as mentioned above, motivated by the MPEG opcodes), L2 (Plexon), FIR matched filter, and IIR matched filter.

The latter was very much an experiment -- IIR filters are efficiently implemented on the blackfin processor, and they generally require fewer taps than their equivalent FIR implementation. To find an IIR equivalent to a given FIR matched filter (whose impulse response closely looks like the actual waveshape, just time-reversed), the filter parameters were simply optimized to match the two impulse responses. To facilitate the search, the denominator was specified in terms of complex conjugate pole locations (thereby constraining the form of the filter), while the numerator coefficients were individually optimized. Note that this is not optimizing given the objective to maximize sorting quality -- rather, it is to make the IIR filter impulse response as close as possible to the FIR matched filter, hence computationally light.

And yet: the IIR filter outperforms the FIR matched filter, even though the IIR filter has 1/3 the coefficients (10 vs 32)! Below is the AUC quality metric for the four methods.

And here are representative ROC curves at varying spike SNR ratios.

The remarkable thing is that even at very low SNR, the matched IIR filter can reliably sort cells from noise. (Note that the acceptable false positive here should be weighted more highly; in the present analysis true positive and false positive are weighted equally, which is decidedly non-Bayesian given most of the time there is no spike.) The matched IIR filter is far superior to the normal MSE to template / L2 norm method -- seems we've been doing it wrong all along?

As for reliably finding spikes / templates / filters when the SNR < 0, the tests above - which assume an equal number of spike samples and non-spike samples -- are highly biased; spikes are not normally sortable when the SNR < 0.


Upon looking at the code again, I realized three important things:

  1. The false positive rate need to be integrated over all time where there is no spike, just the same as the true positive is over all time where there is a spike.
  2. All methods need to be tested with 'distractors', or other spikes with a different shape.
  3. The FIR matched filter was backwards!

Including #1 above, as expected, dramatically increased the false positive rate, which is to be expected and how the filters will be used in the real world. #2 did not dramatically impact any of the discriminators, which is good. #3 alleviated the gap between the IIR and FIR filters, and indeed the FIR matched filter performance now slightly exceeds the IIR matched filer.

Below, AUC metric for 4 methods.

And corresponding ROC for 6 different SNR ratios (note the SNRs sampled are slightly different, due to the higher false positive rate).

One thing to note: as implemented, the IIR filter requires careful matching of poles and zeros, and is may not work with 1.15 fixed-point math on the Blackfin. The method really deserves to be tested in vivo, which I shall do shortly.


More updates:

See www.aicit.org/jcit/ppl/JCIT0509_05.pdf -- they add an 'adjustment' function to the matched filter due to variance in the amplitude of spikes, which adds a little performance at low SNRs.

F(t)=[x(t)kσe˙ 1x(t)kσ] n

Sigma is the standard deviation of x(t), n and k determine 'zoom intensity and zoom center'. The paper is not particularly well written - there are some typos, and their idea seems unjustified. Still the references are interesting:

  • IEEE-238472 (pdf) Optimal detection, classification, and superposition resolution in neural waveform recordings.
    • Their innovation: whitening filter before template matching, still use L2 norm.
  • IEEE-568916 (pdf) Detection, classification, and superposition resolution of action potentials in multiunit single-channel recordings by an on-line real-time neural network
    • Still uses thresholding / spike extraction and L2 norm. Inferior!
  • IEEE-991160 (pdf) Parameter estimation of human nerve C-fibers using matched filtering and multiple hypothesis tracking
    • They use a real matched filter to detect extracellular action potentials.


Update: It is not to difficult to convert FIR filters to IIR filters using simple numerical optimization. Within my client program, this is done using simulated annealing; have tested this using fminsearch in matlab. To investigate the IIR-filter fitting problem more fully, I sliced the 10-dimensional optimization space along pairs of dimensions about the optimum point as found using fminsearch.

The parameters are as follows:

  1. Two poles, stored as four values (a real and imaginary part for each pole pair). These are expanded to denominator coefficients before evaluating the IIR filter.
  2. Five numerator coeficients.
  3. One delay coefficient (to match the left/right shift).

The figure below plots the +-1 beyond the optimum for each axis pair. Click for full resolution image. Note that the last parameter is discrete, hence steps in the objective function. Also note that the problem is perfectly quadratic for the numerator, as expected, which is why LMS works so well.

Note that for the denominator pole locations, the volume of the optimum is small, and there are interesting features beyond this. Some spaces have multiple optima.

The next figure plots +-0.1 beyond the optimum for each axis vs. every other one. It shows that, at least on a small scale, the problem becomes very quadratic in all axes hence amenable to line or conjugate gradient search.

Moving away from planes that pass through a found optima, what does the space look like? E.g. From a naive start, how hard is it to find at least one workable solution? To test this, I perturbed the found optimum with white noise in the parameters std 0.2, and plotted the objective function as before, albeit at higher resolution (600 x 600 points for each slice).

These figures show that there can be several optima in the denominator, but again it appears that a very rough exploration followed by gradient descent should arrive at an optima.

{1168}
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ref: -0 tags: debian linux github persistent ssh authentication date: 07-27-2012 01:40 gmt revision:1 [0] [head]

If you don't want to repeatedly enter in your username/password for github when commiting, you'll want to enable an RSA authetication key.

-- http://www.debian.org/devel/passwordlessssh run

 ssh-keygen 
(with no options).

-- then https://help.github.com/articles/working-with-ssh-key-passphrases

 ssh-keygen -p 
with your github passphrase (I'm not totally sure this is essential).

For me, pull and push aftwerard worked without needing to supply my password. Easy!

{253}
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ref: Mehring-2003.12 tags: BMI LFP MUA SUA Mehring Vaadia date: 07-24-2012 15:54 gmt revision:3 [2] [1] [0] [head]

PMID-14634657[0]Inference of hand movements from local field potentials in monkey motor cortex

  • idea: you get equally good predictions from SUA, LFP, or MUA in decoding a 8-target center-out task.
  • c.f. {1167}

____References____

{1167}
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ref: -0 tags: SUA LFP BMI decoding Donoghue date: 07-24-2012 15:54 gmt revision:0 [head]

PMID-22157115 Decoding 3D reach and grasp from hybrid signals in motor and premotor cortices: spikes, multiunit activity, and local field potentials.

  • Idea: you get more information from SUA (what they call SA) activity than broadband LFPS for predicting reach direction / position for a freely moving monkey.
  • C.F. {253}

{1166}
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ref: Chen-2004.08 tags: brain phantoms agar agarose proxy date: 07-13-2012 01:39 gmt revision:3 [2] [1] [0] [head]

Regarding brain phantoms:

Pia:

Also, both hydrophilic and hydrophobic cleaning appears to be superior to bare tungsten, with the hydrophillic surface treatment slightly superior -- PMID-16686416[2]

____References____

[0] Chen ZJ, Gillies GT, Broaddus WC, Prabhu SS, Fillmore H, Mitchell RM, Corwin FD, Fatouros PP, A realistic brain tissue phantom for intraparenchymal infusion studies.J Neurosurg 101:2, 314-22 (2004 Aug)
[1] Ritter RC, Quate EG, Gillies GT, Grady MS, Howard MA 3rd, Broaddus WC, Measurement of friction on straight catheters in in vitro brain and phantom material.IEEE Trans Biomed Eng 45:4, 476-85 (1998 Apr)
[2] Jensen W, Yoshida K, Hofmann UG, In-vivo implant mechanics of flexible, silicon-based ACREO microelectrode arrays in rat cerebral cortex.IEEE Trans Biomed Eng 53:5, 934-40 (2006 May)

{1165}
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ref: -0 tags: Moxon ceramic array electrode lithography date: 07-12-2012 23:05 gmt revision:3 [2] [1] [0] [head]

IEEE-1275580 (pdf) Ceramic-based Multisite Electrode array for Chronic Single-Neuron Recording

  • Their substrate is polished to 35-50um thick
  • patterned using standard lift-off lithographic techniques
  • four electrodes per shank
  • The ceramic is considerably stiffer than silicon (table) -- 372 Gpa vs. 190 Gpa.

{1164}
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ref: -0 tags: neural recording McGill Musallam electrodes date: 07-12-2012 22:53 gmt revision:0 [head]

http://www.mdpi.com/1424-8220/8/10/6704/pdf NeuroMEMS: Neuro Probe Microtechnologies

  • Good review (as of 2008) of the many different approaches for nervous system recording.

{923}
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ref: Freire-2011.01 tags: Nicolelis BMI electrodes immune respones immunohistochemistry chronic arrays rats 2011 MEA histology date: 06-29-2012 01:20 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-22096594[0] Comprehensive analysis of tissue preservation and recording quality from chronic multielectrode implants.

  • Says what might be expected: tungsten microelectrode arrays work, though the quality gradually declines over 6 months.
  • Histological markers correlated well with recording performance.
  • Shows persistent glial activation around electrode sites + cell body hypertropy.
    • Suggest that loss in recording quality may be due to glial encapsulation.
  • References
    • Szarowski et al 2003 {1028}
    • Ward et al 2009
  • Histology:
    • NADPH-d: nicotinamide adenine dinucleotide phosphate-diaphorase, via beta-NADP
    • CO: cytochrome oxidase, via diamnibenzidine DAB, cytochrome c and catalase.
      • both good for staining cortical layers; applied in a standard buffered solution and monitored to prevent overstaining.
  • Immunohistochemistry:
    • Activated microglia with ED-1 antibody.
    • Astrocytes labeled with glial fibrillary acid protein.
    • IEG with an antibody against EGR-1, 'a well-known marker of calcium dependent neuronal activity'
    • Neurofilament revealed using a monoclonal NF-M antibody.
    • Caspace-3 with the associated antibody
    • Details the steps for immunostaining -- wash, blocknig buffer, addition of the antibody in diluted blocking solution (skim milk) overnight, wash again, incubate in biotinylated secondary antibody, wash again, incubate in avidin-biotin-peroxidase solution.
    • Flourescent immunohistochemistry had biotynlation replaced with alexa Fluor 488-conjugated horse anti-mouse and Alexa Fluor 594-conjugated goat anti-rabbit overnight.

____References____

[0] Freire MA, Morya E, Faber J, Santos JR, Guimaraes JS, Lemos NA, Sameshima K, Pereira A, Ribeiro S, Nicolelis MA, Comprehensive analysis of tissue preservation and recording quality from chronic multielectrode implants.PLoS One 6:11, e27554 (2011)

{307}
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ref: Rousche-1998.07 tags: BMI Utah cat Normann recording electrode MEA histology date: 06-29-2012 01:12 gmt revision:9 [8] [7] [6] [5] [4] [3] [head]

PMID-10223510 Chronic recording capability of the Utah Intracortical Electrode Array in cat sensory cortex.

  • Focus on (surprisingly) chronic recording from the utah array: they want to demonstrate that it works.
  • Platinum coating.
  • insulated with 2-3um polymide.
  • 10 cats, 12 arrays: 2 in S1, 8 in auditory ctx, 2 V1.
  • 11 electrodes connected in each array.
  • After a 6-month implant period, 60% of implanted arrays could still record 'some type of activity'.
  • They were completely targeting neuroprostheses.
    • But acknowledge that 'the presence of fibrous encapsulation and chronic astrogliosis suggests that more research is necessary before the UIEA can be uses as a cornerstone of a neuroprosthetic device for human use.
      • And yet they went through with the human trials?
  • Electrode impedance gave no hint as to the ability of a given electrode to record neural units: many electrodes with average impedance could not record neural activity.
  • Impedances generally decreased , which is not unusual (Schmidt and Bak, 1976).
    • Likely that the polymide had become permeated with water vapor to and equilibrium point. (rather than pinhole leaks or water permeation).
  • Quiet amplifiers: 2uv pk-pk.
  • No significant trend in background activity was noted over the implant durations.
  • In nearly every cat, the dura above the electrode array adhered to the bone flap, and the electrode array adhered to the dura. Therefore, when the bone flap was removed, the UIEA was concurrently explanted from the cortex.
    • Similar to Hoogerwerf and Wise 1994 {1025}
    • The explanted UIEAs typically had become encapsulated, the encapsulation was the cause of the cortical depression.
    • Only 1 did not become encapsulated in dura.
    • This encapsulation explains the gradually varying recording properties -- the electrodes were moving out of the brain.
    • "The capsule which formed around the substrate of the UIEA was usually continuous with the dura, which was enmeshed directly to the overlying skull. The encapsulated array therefore had no freedom of movement with respect to the skull, and this may have caused local trauma which reduced the possibility of recording neural activity. This relative micromovement between the fixed array and the ‘floating’ cortical tissue may also be responsible for sustaining continued growth of the encapsulation as described above."
    • Have tried putting teflon on the top of the Utah array -- did this work?
  • Two UIEAs were not found near the cortical surface -- these two arrays were totally removed from the leptomeningeal space. although originally implanted into the cortex beneath the dura, at the time of sacrafice these arrays were found above the repaired dura, and the implanted cortex showed no evicence of cortical implant.
  • Some electrodes healthy; other showed chronic inflammation.
  • General and intense inflamation in the upper layers of cortex even on their best-performing array; no guarantee that this ctx was working properly, as it is heavily compressed with fibroblasts.
  • Regarding vascluature, see {1024}.
  • Say that the largest impediment is the formation of a capsule around the implant. (Do not mention issue of infection; I guess cats have strong immune systems as well?)
  • Rather good biological discussion and conclusion. worth a re-read. "We currently recommend that the UIEA be used for acute and short-term applications."
    • Not too many follow-ups re teflon or fixing the encapsulation problem: See {1026}
      • Indeed, {1027} doesn't even cite this! Too disastrous?

____References____

{1161}
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ref: -0 tags: springfield downtown library health society date: 05-27-2012 00:44 gmt revision:0 [head]

Just to my left, a woman in a walker rolled into the library, and promptly complained to the police officer on duty about chest pains. The library faces a square in the middle of Springfield where teenagers, shirtless hippies, skateboarders, and other non-mainstream people kill time in the warm afternoon. The library as such is a cool haven to read and access the internet -- several teenagers were playing WoW on the library computers, and I too am tapping into the resource. A possibly adrift artsy-type man of about my age similarly came to conduct his wayward business, having 'just ended up in Springfield', saying it as both and excuse and a badge of pride evincing his free spirit.

The woman is one of the classic types of hypochondriac, and though I'm only listening to them the EMT and police men know this, but they also know that on the off chance of being wrong, not taking the situation seriously could be a disaster. And so they administered simple blood pressure and pulse rate tests, both which seemed normal, then went about convincing her that she needed to be taken to the hospital to be completely checked out, thereby shifting the burden of liability to a place better protected by the standard operating procedure of a battery of tests.

The woman immediately protested, worried about the heavy cost of a ambulance ride, coupled with a paranoia that she would lose her walker. To this the EMT -- a short woman with her practical ponytail shoved through a baseball cap, as often they do -- let glints of irritation show through, asking her repeatedly to decide which hospital she wished to go to, and then asking her to arrange another means to the hospital. The woman protested, but the EMT could scarecly be blamed -- she is stuck in a system not of her design -- and somehow the smooth-souled librarian, who before had been placating library customers by putting holds on books, convinced both parties to go to the nearest hopsital. How exactly this was done I'll forever remain in ignorance, for another ambulance spun through the downtown circle at that instant, scattering sports cars, stopping sedans, and causing the skaters to pause their idling and look.

The incident vaguely reminds me when I had similar issues in Brooklyn, when i was sufficiently pained to drive my ass through the dirty orange-lit streets to a hospital in Williamsburg. They proceeded to do drug tests on me, despite my insistences, but everything checked out fine. In retrospect, the pain was likely heartburn antagonized by psychological isolation; this was before I really learned to listen to myself, and take care of the social and more basic physiological needs. The walker woman fell through these same cracks in a likely preventable but now very expensive way.

Meanwhile, a large black transsexual and a wrinkly white guy walk hurriedly past the plate glass windows of the library, talking animatedly. They may be in a fissure of sorts, but i doubt they consider it a fall...

{1160}
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ref: -0 tags: william james quotes date: 04-30-2012 15:40 gmt revision:0 [head]

And the faculty of voluntarily bringing back a wandering attention over and over again is the very root of judgement, character, and will. No one is compos sui if he have it not. An education should improve this faculty would be education par excellence".

{1159}
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ref: -0 tags: loops feedback arcs video game programming date: 04-30-2012 15:12 gmt revision:0 [head]

I highly agree with this philosophy / this deconstruction of the flow of information in human structures: http://www.lostgarden.com/2012/04/loops-and-arcs.html

On criticism as a meta-arc game:

"In the past I've discussed criticism as a game that attempts to revisit an arc repeatedly and embellish it with additional meaning. The game is to generate essays superficially based on some piece of existing art. In turn, other players generate additional essays based off the first essays. This acts as both a referee mechanism and judge. Score is accumulated via reference counts and by rising through an organization hierarchy. It is a deliciously political game of wit that is both impenetrable to outsiders and nearly independent of the actual source arcs. Here creating an arc becomes a move in the larger game. "

{1158}
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ref: -0 tags: bees energy harvesting honey date: 04-11-2012 06:02 gmt revision:2 [1] [0] [head]

This morning hundreds of bees were swarming outside my front door -- a fact is not without reason, as my roommate makes honey, and her hive just today outgrew the apiary. Hence the hive split this morning, and one queen be left to wait on a branch outside while scouts searched for good places to build a new colony; meanwhile hundreds of non-scout workers were swarming around her.

Bees are amazing. Anyway, a friend sent a link to an article describing how to generate microwatts of energy off a flying insect, which led me to wonder how much energy those bees could have been producing instead of milling protectively about their queen.

  • number of bees : 1000
  • power, with direct connection to flight muscles: 400 uW
  • total possible power: 400mW
  • kCal in a tablespoon (21g) of honey: 64
    • in joules: 270kJ
  • Length of time it would take for 500 madly flapping bees (1) to generate the energy within a tablespoon of honey: 375 hours (15.6 days)
  • Yield of honey from a large, productive hive: 150 lbs / year (2)
    • in watts: 27.8 W
    • number of bees: 20000 (2)
    • factor better than energy harvesting: 3.5

Conclusion: let them make honey :-)


(1) Half the bees visible were resting on leaves, not madly flapping.

(2) Rough wiki-google estimate.

{1157}
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ref: -0 tags: spike sorting variational bayes PCA Japan date: 04-04-2012 20:16 gmt revision:1 [0] [head]

PMID-22448159 Spike sorting of heterogeneous neuron types by multimodality-weighted PCA and explicit robust variational Bayes.

  • Cutting edge windowing-then-sorting method.
  • projection multimodality-weighted principal component analysis (mPCA, novel).
    • Multimodality of a feature is by checking the informativeness using the KS test of a given feature.
  • Also investigate graph laplacian features (GLF), which projects high-dimensional data onto a low-dimensional space while preserving topological structure.
  • Clustering based on variational Bayes for Student's T mixture model (SVB).
    • Does not rely on MAP inference and works reliably over difficult-to sort data, e.g. bursting neurons and sparsely firing neurons.
  • Wavelet preprocessing improves spike separation.
  • open-source, available at http://etos.sourceforge.net/

{967}
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ref: Rosin-2011.1 tags: PD closed loop DBS globus pallidus oscillations STN Vaadia heterodyne beta date: 03-26-2012 16:23 gmt revision:16 [15] [14] [13] [12] [11] [10] [head]

PMID-22017994[0] Closed-loop deep brain stimulation is superior in ameliorating parkinsonism.

  • Also reviewed by Rui Costa: PMID-22017983[1]
    • Good, brief review -- with appropriate minimal references.
  • Partial goal of the work: parameter determination and optimization can take a long time, and are typically only done every 3-6 months initially. But the actually changes of activity / responsiveness occur on a faster timescale in the disease, even instantaneous; other studies have shown that updating the stimulation parameters more frequently helps patients. (of course, this is a different form of closed-loop).
  • Pathology: intermittent neuronal oscillations in the basal ganglia and motor cortex commonly observed.
    • In MPTP treated primates these oscillations occur in the tremor band (theta, 4-7Hz), and double-tremor band (9-15Hz, alpha) (Bergman et al 1994 {120}, Ras et al 2000 PMID-11069964 ).
    • Actual pathology still inconclusive; talk about disruption of pathological patterns and 'focal inhibition', but this is no thorough review by any estimate.
  • "In recent years, the role of pathological discharge patterns in the parkinsonian brain has emerged as pivotal in the disease pathology
    • Eusebio and Brown, 2007;
    • Hammond et al., 2007;
    • Kuhn et al., 2009;
    • Tass et al., 2010;
    • Vitek, 2008;
    • Weinberger et al., 2009;
    • Wichmann and DeLong, 2006;
    • Zaidel et al., 2009.
    • Automatic systems should disrupt this pattern of discharge (Feng 2006, Tass 2003).
      • However, the role of these oscillations as the neuronal correlate of PD motor symptoms is still debated (Hammond et al., 2007; Leblois et al., 2007; Lozano and Eltahawy, 2004; McIntyre et al., 2004; Tass et al., 2010; Vitek, 2002; Weinberger et al., 2009 {1089}).
  • 2 african green monkeys, MPTP treatment.
  • Recorded from GPi & M1 (127 and 210 neurons); stimulated GPi, 7 pulses at 130Hz, 80ms after spike from reference area (M1 or GPi).
    • 80ms delay coincided with the next double-tremor oscillatory burst (12.5Hz)
    • State of neuronal oscillatory discharge of cortico-BG loops often accompanied by synchronization btw cortex and BG (see also quote below)
    • GPi following M1 activity superior (GP|M1 in their notation).
    • single pulses did not work.
    • Stimulation: 80uA 200us bipolar biphasic (small and short!).
  • Stimiulus protocol (M1 trigger) abolishes oscillatory activity in recorded GPi neurons.
  • Also reduced akinesia as measured with an accelerometer & decreased firing rate in the GPi.
    • Both work better than constant 130Hz DBS.
    • Also much more irregular: fewer stimulation pulses at longer latency.
  • Open loop control (the control) did much less regarding FR oscillations & bursts and reduction in firing rate.
    • Dorval et al 2010: increasing the stimulus irregularity of open-loop DBS decreases its beneficial clinical effectcs. (also Baker et. al 2011).
  • GP train stimulation triggered on GP firing significantly worsened akinesia, despite the fact that the pallidial FR decreased.
    • Treatment increased spike oscillation at double-tremor frequency in M1.
  • Oscillations more important than firing rate changes (new vs. old hypothesis).
    • pallidal oscillatory activity was not correlated to the pallidal discharge rate either before or during the application of standard DBS or GP|M1.
  • In our data, may have double-frequency tremor effects. Heterodyne should detect this.
    • "Studies on the dynamics of the entire cortico-basal ganglia loops have frequently reported the emergence of intra-and interloop component synchrony and oscillatory activity."
    • "Nevertheless, the somewhat intuitive connection between neuronal oscillations and parkinsonian motor symptoms, which include rest and action tremors, has been challenged (Hammond et al., 2007 PMID-17532060 ; Leblois et al., 2007 {1146}; Lozano and Eltahawy, 2004; Tass et al., 2010 {1147}; Vitek, 2002; Weinberger et al., 2009). For instance, while the parkinsonian rest tremor occurs mainly at the 4–7 Hz frequency band, the oscillatory neuronal activity is observed in several characteristic frequency bands in both human PD patients (Hutchison et al., 2004) {1156} and animal models (Bergman et al 1994, Gubellini et al 2009) {1074}"
      • This also has import to our heterodyne results!
    • Synchrony between globus pallidus and M1 is dynamic and state-dependent (whatever that means -- have to check the refs, Levy et al 2002 {829}, Timmerman et al 2003 {1087})
  • Quote: "... it suggests that reduction of the abnormal parkinsonian oscillatory activity could in fact be the underlying mechanism by which DBS exerts its action and brings about the associated clinical improvement."
  • Neuronal oscillatory activity occurs as high as the beta-band, 15-35Hz, hence clinical app. would need a tuned antiphase lag.
  • Suggest that the closed-loop treatment may be applicable to other diseases with characteristic firing patterns, like schizophrenia.
  • Since synchonization and oscillations hend to coincide, .. we found this too.
    • Heimer et al 2006 {1076}: oscillations and synchrony can exist independently.
  • Figure suck. Text inconsistent and frequently too small.
    • Wavelet spectrograms are nice tho.

Other thoughts:

  • Somebody should measure the transfer function of the BG / cortical loop. H(z).
  • This seems like adding a comb-filter or zero at a particular frequency: GP|GP stimluation exacerbated the effect, GP|M1 minimized the effect as there is a negation in there. (e.g. GP actviity decreases firing of M1, and vice versa).

____References____

[0] Rosin B, Slovik M, Mitelman R, Rivlin-Etzion M, Haber SN, Israel Z, Vaadia E, Bergman H, Closed-loop deep brain stimulation is superior in ameliorating parkinsonism.Neuron 72:2, 370-84 (2011 Oct 20)
[1] Santos FJ, Costa RM, Tecuapetla F, Stimulation on demand: closing the loop on deep brain stimulation.Neuron 72:2, 197-8 (2011 Oct 20)

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ref: -0 tags: Hutchison oscillations basal ganglia beta gamma globus pallidus date: 03-26-2012 16:21 gmt revision:2 [1] [0] [head]

PMID-15496658 Neuronal oscillations in the basal ganglia and movement disorders: evidence from whole animal and human recordings.

  • This is a review / mini-symposium (only 3 pages)
    • Cites other Hutchison papers: 1997, 1998.
  • Critique classical hypothesis in that GPi firing does not increase that much, 10-22% in animal models. IT explains akinesia and bradykinesia, but not rigidity or tremor. (This was 8 years ago, remember!)
    • Plus, most neurons have intrinsic pacemaker-like properties that sets the rate of firing in the absence of synaptic input. (Bevan et al 2002).
  • Oscillations:
    • Alpha band enhanced after MPTP treatment in green monkeys and in the STN of some PD patients with tremor at rest.
    • Higher frequency oscillations (beta, 15-25Hz) can be observed in some patients without resting tremor.
    • Much slower oscillations discovered by Judith Walters, 6 OHDA rat (0.3 - 2Hz).
    • Also ultralow, multisecond oscillations, which appear in dopamine stimulated rats. (Ruskin et al 1999a,,b, 2003).
      • Lesion of the STN was not found to change these ultralow oscillations, but did modify the connectivity between GP and SNr.
    • Courtemanche et al 2003 studied the possible normal physiological function for oscillations in basal ganglia networks.
      • Beta band decreased during saccadic eye movements.
      • LFP syncronization showed task-related decrease, but only in sites engaged in the task, as evicenced by saccade-related activity.
  • Boraud tested gradual small-dose administration of MPTP toxin:
    • Minimal changes in the average firing rate of GPi neurons
    • Oscillatory activity between 4-9 and 11-14 Hz, with differences between monkeys.
      • Oscillations increased with symptom presentation.
  • Goldberg et al 2004: analyzed coherence between EEG and BG LFP; surmise that in the PD condition the basal ganglia and cortex become more closely entrained by global brain dynamics, which are reflected in the widespread local field potentials.
  • Peter Brown: oscillations in the beta band are enhanced to such an extent in Parkinson's disease that voluntary movements are not generated because motor command for initiation cannot override the enhanced oscillatory state.
    • That is, movement initiation corresponds to beta-band desynchronization, and movement command cannot 'break through'.

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ref: -0 tags: hippocampus theta oscillations memory date: 03-18-2012 18:09 gmt revision:0 [head]

PMID-21696996 The hippocampus: hub of brain network communication for memory

  • Their hypothesis: memory encoding is dominated by theta oscillations 6-10 Hz; during inactivity, hippocampal neurons burst synchronously, creating sharp waves, theoretically supporting memory consolidation.
  • (They claim): to date there is no generally accepted theoretical view on memory consolidation.
  • Generally it seems to shift from hippocampus to neocortex, but still, evidence is equivocal. (Other than HM & other human evidence?)
  • Posit a theory based on excitation ramps of reverse-replay, which seems a bit fishy to me (figure 3).
  • Didn't know this: replay in visual and PFC can be so precise that it preserves detailed features of the crosscorrelograms between neurons. [58, 65, 81].

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ref: -0 tags: hippocampus theta oscillations date: 03-18-2012 17:34 gmt revision:2 [1] [0] [head]

PMID-11832222 Theta Oscillations in the Hippocampus

  • Theta-alpha oscillations have been found in 'all mammals to-date, including humans. (Hence conserved, hence possibly essential).
    • Prevalent in REM sleep.
    • Present in slices bathed in carbachol, too.
    • As well as locomotor activities; but not usually when the animal is resting.
  • Other reviews: Bland 1986, VAnderwolf 1988, Lopes da Silva et al 1990, Buzaki et al 1994 Stewart and Fox 1990, Vinogradova 1995, Vertex and Kocsis 1997.
    • Modeling reviews used passive cable properties; actually, it seems neurons, and their dendrites are have active conductances & active oscillatory features.
  • Theta oscillations most strongly present in CA1
  • Along similar lamina, oscillations are similar.
  • Osc. visible in cortical structures ...
    • subicular complex, entorhinal cortex, perirhinal cortex, cingulate cortex, amygdala -- though none of these structures are capable of generating theta oscillations intrinsically.
  • Also apparent in subcortical structures,
    • Dorsal raphe nucleus, ventral tegmental nucleus, and anterior thalamic nuclei. None of these seem required for oscillation, however:
  • Oscillations may emanate from the medial-septum-diagonal band of Broca (MS-DBB); lesion inactivates theta oscillations in all cortical areas, but the relative role is uncertain, as MS-DBB oscillations may require hippocampal and entorhinal afferents.
    • EPSPs brought about by the MS-DBB cholinergic neurons on hippocampal pyramidal cells cannot be responsible for the atrophine-sensitive form of theta.
    • That said, even though atrophine treatment only modestrly affects theta, it is reduced several-fold after selective neurotoxin elminiation of MS-DBB cholinergic cells -- maybe it's nicotinic synapses?
  • Drugs:
    • Theta can be blocked by GABA antagonist (picrotoxin, induces epilepsy) or agonist (pentoparbital anesthesia).
    • Many other drugs affect oscillations.
    • Broken down into atrophine-sensitive and atrophine-resistant oscillations.
      • (Atrophine blocks muscarinic Ach receptors).
    • Amplitude and frequency of theta does not appreciably change even after large doses of systematic muscarinic blockers.
      • Same drugs abolish theta under anesthesia.
    • The neurotransmitter and receptor causative in theta have never been clearly determined.
  • Theta in CA3 is much smaller than in CA3:
    • Distal dendritic arbor of CA3 pyramidal cells is considerably smaller than that of CA1 pyramidal neurons.
    • CA3 pyramidal neurons receive perisomatic exitation near their somata from the large mossy terminals of granule cells.
      • Regarding this, size of mossy fiber projection correlates well with spatial ability in mice, possibly causative. link (note: used the dryland radial maze, more appropriate for non-swimming mice!)
    • Intrahippocampal oscillator (CA3?) can change its frequency and phase relatively independently from the extrahippocampal (entorhinal) theta inputs.
  • CA1 interneurons discharge on the descenting phase of theta in the pyramidal cell layer, and are assumed to be responsible for the increased gamma of this phase.
  • CA1 pyramidal cells discharge on the negative phase (makes sense) of theta as recorded from the CA1 pyramidal cell layer.
    • Phase fluctuation of spikesis not random and correlates with behavioral varaibles.
      • Stronger excitation = more spikes earlier in the theta negative phase.
    • Firing of place cells varies systematically with animal position and theta phase -- there is a phase precession.
      • Seems as though place is encoded in both which cell is firing as well as when in theta.
      • alternately, this may be an effect of the CA3 oscillator running slightly faster than the extrinsic oscillator.

Original model for theta oscillation creation (figure 2):

  • Note that all oscillations require a dipole which periodically inverts along it's axis, as is required in a conductive solution.
    • And yet there is no 'null' zone in theta oscillation, as dipole would imply. Rather, there is a gradual shift, more like a traveling wave.
  • Dendrites are passive cables, LFP generated by summed activity of IPSP and EPSP on soma and dendrites.
    • Excitation from perforant path,
    • Inhibition from septum to feed-forward inhibitory neuron inputs.
  • That said, the model is not completely consistent with experimental evidence:
    • The highest probability of discharge in the behaving rat occurs around the positive peak of theta recorded at the level of the distal dendrites, corresponding to the negative phase in the pyramidal level. (Remember, spiking corresponds to sodium influx, hence decreased extracellular +)
    • Cells may oscillate by themselves, without input.
    • The cell connections within the hippocampus matter a lot, too.

LTP:

  • Induction is present / optimal when the spacing between pulses is 200ms.
    • Priming can be only one pulse!
    • Not clear how this works - endogenous cannabanoids?
  • Theta oscillation may provide a mechanism for bringing together time afferent inducing depolarization and dendritic invasion of fast spikes.

Conclusions:

  • A theta cycle may be considered an information quantum, allowing the exchange of information among the linked members in a phase-locked manner. ...
  • This discontinuous mode of operation may be a unique solution to temporally segregate and link neuronal assemblies to perform various operations.
  • Notable support of this hypothesis:
    • Theta cycle phase resets upon sensory stimulation
    • Motor activity can become theta locked.

Misc:

  • Ketamine blocks NMDA receptors.
  • Granule cells can be eliminated by neonatal X-ray exposure. (why?)

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ref: -0 tags: impedance digital transmission line date: 03-14-2012 22:20 gmt revision:0 [head]

http://web.cecs.pdx.edu/~greenwd/xmsnLine_notes.pdf -- Series termination will work, provided the impedance of the driver + series resistor is matched to the impedance of the transmission line being driven.

School has been so long ago, I've forgotten these essentials!

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ref: Hashimoto-2003.03 tags: cortex striatum learning carmena costa basal ganglia date: 03-07-2012 23:18 gmt revision:3 [2] [1] [0] [head]

PMID-22388818 Corticostriatal plasticity is necessary for learning intentional neuroprosthetic skills.

  • Trained a mouse to control an auditory cursor, as in Kipke's task {99}. Did not cite that paper, claimed it was 'novel'. oops.
  • Summed neuronal firing rate of groups of 2 or 4 M1 neurons.
    • One grou increased the frequenxy with increased firing rate; the other decreased tone with increasing FR.
  • Removal of striatal NMDA receptors impairs the ability to learn neuroprosthetic skills.
    • Hence, they argue, cortico-striatal plastciity is required to learn abstract skills, such as this tone to firing rate target acquisition task.
  • Auditory feedback was essential for operant learning.
  • Controlled by recording EMG of the vibrissae + injection of lidocane into the whisker pad.
  • One reward was sucrose solution; the other was a food pellet. When the rat was satiated on one modality, they showed increased preference for the opposite reward. Clever control.
  • Noticed pronounced oscillatory spike coupling, the coherence of which was increased in low-frequency bands in late learning relative to early learning (figure 3).
  • Genetic manipulations: knockin line that expresses Cre recombinase in both striatonigral and striatopallidal medium spiny neurons, crossed with mice carrying a floxed allele of the NMDAR1 gene.
    • These animals are relatively normal, and can learn to perform rapid sequential movements, but are unable to learn precise motor sequences.
    • Acute pharmacological blockade of NMDAR did not affect performance of the neuroprosthetic skill.
    • HEnce the deficits in the transgenic mice are due to an inability to perform the skill.

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ref: -0 tags: meng poon wireless power transfer date: 03-07-2012 22:23 gmt revision:0 [head]

IEEE-4353634 (pdf) Optimal Operating Frequency in Wireless Power Transmission for Implantable Devices

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ref: Hashimoto-2003.03 tags: DBS STN subthalamic nucleus globus pallidus electrophysiology date: 03-07-2012 21:57 gmt revision:3 [2] [1] [0] [head]

PMID-12629196[0] Stimulation of the Subthalamic Nucleus Changes the Firing Pattern of Pallidal Neurons

  • why does STN stim work? investigated the effects of STN HFS on neuronal activity of GPi and GPe.
  • monkeys were treated with MPTP
  • used a scaled-down version of human DBS stimulator (cool!)
  • high frequency stimulation resulted in stimulus-synchronized regular firing pattern, plus an overall increase in pallidal firing rate.
    • they think that this synchrony may underlie the beneficial effect of HFS in the STN
  • only behavior was, apparently, what amplitude and frequency were required to alleviate parkinsonian symptoms.
  • if i do DBS in normal monkeys, is there anything to say that the effect will be similar or comparable to treatment stimulation?
  • they remind us that HFS = lesion in terms of alleviating symptoms of parkinsons.

____References____

[0] Hashimoto T, Elder CM, Okun MS, Patrick SK, Vitek JL, Stimulation of the subthalamic nucleus changes the firing pattern of pallidal neurons.J Neurosci 23:5, 1916-23 (2003 Mar 1)

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ref: Jarosiewicz-2008.12 tags: Schwartz BMI learning perturbation date: 03-07-2012 17:11 gmt revision:2 [1] [0] [head]

PMID-19047633[0] Functional network reorganization during learning in a brain-computer interface paradigm.

  • quote: For example, the tuning functions of neurons in the motor cortex can change when monkeys adapt to perturbations that interfere with the execution (5–7) or visual feedback (8–10) of their movements. Check these refs - have to be good!
  • point out that only the BMI lets you see how the changes reflect changes in behavior.
  • BMI also allows pertubactions to target a subset of neurons. apparently, they had the same idea as me.
  • used the PV algorithm. yeck.
  • perturbed a select subset of neurons by rotating their tuning by 90deg. about the Z-axis. pre - perturb - washout series of experiments.
  • 3D BMI, center-out task, 8 targets at the corners of a cube.
  • looked for the following strategies for compensating to the perturbation:
    • re-aiming: to compensate for the deflected trajectory, aim at a rotated target.
    • re-waiting: decrease the strength of the rotated neurons.
    • re-mapping: use the new units based on their rotated tuning.
  • modulation depths for the rotated neurons did in fact decrease.
  • PD for the neurons that were perturbed rotated more than the control neurons.
  • rotated neurons contributed to error parallel to perturbation, unrotated compensated for this, and contributed to 'errors' in the opposite direction.
  • typical recording sessions of 3 hours - thus, the adaptation had to proceed quickly and only online. pre-perturb-washout each had about 8 * 20 trials.
  • interesting conjecture: "Another possibility is that these neurons solve the “credit-assignment problem” described in the artificial intelligence literature (25–26). By using a form of Hebbian learning (27), each neuron could reduce its contribution to error independently of other neurons via noise-driven synaptic updating rules (28–30). "
    • ref 25: Minsky - 1961;
    • ref 26: Cohen PR, Feigenbaum EA (1982) The Handbook of Artificial Intelligence; 27 references Hebb driectly - 1949 ;
    • ref 28: ALOPEX {695} ;
    • ref 29: PMID-1903542[1] A more biologically plausible learning rule for neural networks.
    • ref 30: PMID-17652414[2] Model of birdsong learning based on gradient estimation by dynamic perturbation of neural conductances. Fiete IR, Fee MS, Seung HS.

____References____

[0] Jarosiewicz B, Chase SM, Fraser GW, Velliste M, Kass RE, Schwartz AB, Functional network reorganization during learning in a brain-computer interface paradigm.Proc Natl Acad Sci U S A 105:49, 19486-91 (2008 Dec 9)
[1] Mazzoni P, Andersen RA, Jordan MI, A more biologically plausible learning rule for neural networks.Proc Natl Acad Sci U S A 88:10, 4433-7 (1991 May 15)
[2] Fiete IR, Fee MS, Seung HS, Model of birdsong learning based on gradient estimation by dynamic perturbation of neural conductances.J Neurophysiol 98:4, 2038-57 (2007 Oct)

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ref: -0 tags: implicit motor sequence learning basal ganglia parkinson's disease date: 03-06-2012 22:47 gmt revision:2 [1] [0] [head]

PMID-19744484 What can man do without basal ganglia motor output? The effect of combined unilateral subthalamotomy and pallidotomy in a patient with Parkinson's disease.

  • Unilateral lesion of both STN and GPi in one patient. Hence, the patient was his own control.
    • DRastically reduced the need for medication, indicating that it had a profound effect on BG output.
  • Arm contralateral lesion showed faster reaction times and normal movement speeds; ipsilateral arm parkinsonian.
  • Implicit sequence learning in a task was absent.
  • In a go / no-go task when the percent of no-go trials increased, the RT speriority of contralateral hand was lost.
  • " THe risk of persistent dyskinesias need not be viewed as a contraindication to subthalamotomy in PD patients since they can be eliminated if necessary by a subsequent pallidotomy without producting deficits that impair daily life.
  • Subthalamotomy incurs persistent hemiballismus / chorea in 8% of patients; in many others chorea spontaneously disappears.
    • This can be treated by a subsequent pallidotomy.
  • Patient had Parkinsonian symptoms largely restricted to right side.
  • Measured TMS ability to stimulate motor cortex -- which appears to be a common treatment. STN / GPi lesion appears to have limited effect on motor cortex exitability 9other things redulate it?).
  • conclusion: interrupting BG output removes such abnormal signaling and allows the motor system to operate more normally.
    • Bath DA presumably calms hyperactive SNr neurons.
    • Yuo cannot distrupt output of the BG with compete imuntiy; the associated abnormalities may be too subtle to be detected in normal behaviors, explaniing the overall clinical improbement seen in PD patients after surgery and the scarcity fo clinical manifestations in people with focal BG lesions (Bhatia and Marsden, 1994; Marsden and Obeso 1994).
      • Our results support the prediction that surgical lesions of the BG in PD would be associated with inflexibility or reduced capability for motor learning. (Marsden and Obeso, 1994).
  • It is better to dispense with faulty BG output than to have a faulty one.

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ref: bookmark-0 tags: basal ganglia dopamine reinforcement learning Graybeil date: 03-06-2012 18:14 gmt revision:4 [3] [2] [1] [0] [head]

PMID-16271465 The basal ganglia: learning new tricks and loving it

  • BG analogous to the anterior forebrain pathway (AFP), which is necessary for song learning in young birds. Requires lots of practice and feedback. Studies suggest e.g. that neural activity in the AFP is correlated with song variability, and that the AFP can adjust ongoing activity in effector motor pathways.
    • LMAN = presumed homolog of cortex that receives basal ganglia outflow. Blockade of outflow from LMAN to RA creates stereotyped singing.
  • To see accurately what is happening, it's necessary to record simultaneously, or in close temporal contiguity, striatal and cortical neurons during learning.
    • Pasupathy and biller showed that changes occur in the striatum than cortex during learning.
  • She cites lots of papers -- there has been a good bit of work on this, and the theories are coming together. I should be careful not to dismiss or negatively weight things.
  • Person and Perkel [48] reports that in songbirds, the analogous GPi to thalamus pathway induces IPSPs as well as rebound spikes with highly selective timing.
  • Reference Levenesque and Parent PMID-16087877 who find elaborate column-like arrays of striatonigral terminations in the SNr, not in the dopamine-containing SNpc.

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ref: Rouse-2011.06 tags: BMI chronic DBS bidirectional stimulator Washington Medtronic ASIC translational date: 03-05-2012 23:56 gmt revision:3 [2] [1] [0] [head]

PMID-21543839[0] A chronic generalized bi-directional brain-machine interface.

  • Using a commercial neurostimulator package & battery etc.
  • "A key goal of this research prototype is to help broaden the clinical scope and acceptance of NI techniques, particularly real-time brain state detection" Good purpose! good work!
  • Augments the stimulator with 4 channels of ECoG/LFP + accelerometer + wireless telemetry.
    • Can be used to detect parkinsons state or pre-epileptiform behavior.
      • Much of this has been though of before, it just took the technology to catch up & a group to make it.
    • Chronic data is needed from humans -- animal models are often inadequate.
  • Tested in a primate for brain control of a cursor: 1D control using ECoG.
    • Good Left/right ROC, actually.
    • A large cost is simply the clinical testing; hence they piggy-back on an existing design.
    • There should be more research-industry collaborations like this.
  • impressive specs.
  • SVM classification algorithm (only consumed 10uW!) for data compression.
  • short-time Fourier transform for extracting the power over a given band. This using a modified chopper-amplification scheme. Output data has a bandwidth of less than 5Hz, which greatly reduces processing requirements.
  • Lots of processing on the BASIC chip, much like here.
  • Also see the press release

____References____

[0] Rouse AG, Stanslaski SR, Cong P, Jensen RM, Afshar P, Ullestad D, Gupta R, Molnar GF, Moran DW, Denison TJ, A chronic generalized bi-directional brain-machine interface.J Neural Eng 8:3, 036018 (2011 Jun)

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ref: Mink-1996.11 tags: empty date: 03-05-2012 23:35 gmt revision:2 [1] [0] [head]

see {1117}

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ref: Tass-2010.02 tags: empty date: 03-05-2012 23:33 gmt revision:2 [1] [0] [head]

see {1147}

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ref: Mink-1996.11 tags: basal ganglia review parkinsons STN DBS date: 03-05-2012 23:33 gmt revision:13 [12] [11] [10] [9] [8] [7] [head]

PMID-9004351[0] The basal ganglia: focused selection and inhibition of competing motor programs.

  • Plenty of focus on diseased states, but normal function is unclear.
  • basal ganglia do not generate motor programs; that is the task of the cerebrum / cerebellum (based on timing).
  • review posits that the inhibitory output of the BG acts to seletively inhibit competing motor mechanisms in order to prevent them from interfering with voluntary movements that are generated by other CNS structures.
  • Involvement of the BG in motor control old -- dates back to Kinner Wilson describes pathology of rigidity and tremor following lenticular degeneration.
    • Thought that the pyramidal system was new and plastic, whereas the extrapyramidal system was archaic and postural / static.
    • Extrapyramidal system is actually prepyramidal, too.
  • Striatum.
    • receives excitatory input from all of the cerebrum except primary auditory and visual cortices.
    • cortical projections terminate in longitudinal bands.
    • in reciprocally connected areas of frontal, temporal, and parietal cortex terminate in adjacent or interdigitating zones in the striatum.
    • somatotopy in projections: areas receiving input from the face area of sensory or motor cortex are separate from those receiving input from the arm area.
    • The zones themselves overlap / are interdigitated, but not completely.
    • 95% of the cells are medium spiny neurons (MSN).
      • The remainder are glutamine from centromedian and parafasicular nuclei of the thalamus, cholinergic input from large aspiny neurons, GABA from neighboring MSTs, and dopamine from SNpc.
    • When Flaherty and Graybiel (1994) PMID-7507981[1] injected retrograde tracer into GPi and anterograde tracer into sensory or motor cortex they were able to demonstrate multiple striatal zones that were labeled from both injections. This suggests that information is sent from cortex to striatum in a multiply convergent and divergent pattern with reconvergence in GPi after processing in the striatum (Fig. 2).
    • Caudate projects to SNpc
    • Putamen projects to the GPi.
    • Acetylcholine: there is a patchy distribution of heavily and lightly stained regions, corresponding to striosomes and the matrix.
      • Dendrites of most MSN are restricted to a single compartment.
      • both striosomes and matrix receive input from the SNpc, but only the striosomes project back to the SNpc.
      • Striosomes can affect the matrix via large aspiny neurons, AChe, 1-2% of the total striatal population.
    • One striatal cell receives input from thousands of cortical cells.
      • Activation of a MSN appears to require concurrent excitatory input from a large number of cortical afferents.
    • MSNs have a low resting firing rate of 0.1 - 1 Hz -- strong resting potassium current.
      • Cells can switch between two stable states: hyperpolarized -80mV and moderately polarized -50mV.
      • This appears to be stabilized by large aspiny cholinergic neurons (?)
  • D1 increases cAMP, D2 usually decreases cAMP. both expressed on MSN; some suggest differentially, based on anatomical target.
  • STN
    • dendrites up to 1200um.
    • in GPi and SNpr, STN axon collaterals branch to ensheath the cell bodies and proximal dendrites of their target neurons.
    • each axon from the subthalamic nucleus ensheathes many GPi neurons.
    • Input primarily from the oculo-and somato-motor areas of the frontal lobes.
    • does not seem to have much intrinisic processing; it's more of a relay.
  • GPi:
    • About 70% send axon collaterals to both thalamus and brainstem.
    • Projects to ventrolateral (Vlo) and ventral anterior nucleus (VApc).
    • Little overlap in projections fom the basal ganglia and the cerebellum in the thalamus.
    • collaterals of most GPi axons projecting to thalamus project to an area at the junction of the midbrain and pons adjacent to the pedunculopontine nucleus (PPN). Some call it the "midbrain extrapyramical area", which projects to the reticulospinal motor system.
  • GPe:
    • Most output inhibitory to STN; most input from the striatum and STN.
    • Also output to GPi and SNr.

Electrophysiology:

  • In the striatum, cells fire in relation to both the direction of movement (25%) as well as the direction of force (50%) (Crutcher and DeLong 1984b PMID-6705862[2]).
  • More cells fire during slow "ramp" movements than during fast "ballistic" movements, possibly due to their relation to proximal muscle activity, or due to force / speed modulation.
  • Cells fire phasically relative to cue, to movement, or after movement / before the next movement ("set" neurons). .
  • In the putamen, most activity is late, though there is a distribution anterior-posterior, with anterior cells more likely to fire early; these are possibly of cognitive origin.
  • In the striatum, activity has been found to context-dependent: e.g. cells respond to touch, but only if it is within the context of a movement.
    • Romo et. a.l 1992 controlled for this wrt externally triggered movements vs. self-initiated movements.
    • Within the caudate, Hikosaka et al 1989a described cell firing in the caudate relative to delayed, cued, and remembered saccades.
      • context-dependent activity is a feature of the striatum, but not necessarily the function.
  • Cholinergic large aspiny neurons appear to have no relation to movement.
    • But they do fire in relation to sensory input or to reward.
    • Since one effect of cholinergic input to MSN is to stabilize the present state, in the situation where the current behavior results in a reward, activity of the cholinergic interneurons would tend to reinforce the ongoing pattern of striatal activity. Interesting!! memory!

STN:

  • tonically active, with a resting rate of 20 Hz.
  • somatotopic organization, lower extremity dorsal and face / eyes ventral.
  • neurons increase firing rate in relation to eye or limb movement. (Matsumura et al 1992, Wichmann et al 1994a [3]).
  • In monkeys treained to perform elbow movements, 60-75% STN neurons had activity related to movement direction (Georgopoulos et al 1983) (Wichmann et al 1994a).
    • Unclear proportion responded to passive movement: 20% former, 50% latter.
  • It is not known to what degree STN neurons discharge in relation to other movement parameters. Only 1 study, with only 7 neurons, had some correlation to velocity ( Georgopoulos 1983)
  • Onset of activity slower than M1 or EMG.
  • Ventral STN: of all task-related neurons, 23% were related to saccades, 39% related to visual fixation, 15% to visual sensory responses.
  • Matsumura 1992 shows that 52% of STN neurons had activity related to maintained eye position but not to saccades.
    • STN supresses saccades: STN excites SNr which inhibits collicular neurons involved in saccade generation.
  • in MPTP monkeys, ablation or inactivation of the STN cauyses transient diskinesia but when it resolved monkeys were able to move normally. (BErgman et al 1990; Wichmann et al 1994b).

GPi:

  • activity does not correlate with physical parameters of movement.
    • no consistent relationship between GPi activity and joint position, force production, movement amplitude, or movement velocity during wrist movement.
    • little correlation of GPi output with EMG profiles either.
  • Ramp and ballistic movements: equal amounts of control.

SNr:

  • All involved in eye movements are tonically active.
  • virtually all have been reported to decrease activity during eye movement.
    • Still yet: SNr show firing rate decreases while GPi show firing rate increases.
    • Decreased SNr discharge results in disinhibition in the superior colliculus to initiate saccades.
    • Could also be that the SC generates simultaneous eye and head movements, and the SNr helps to inhibit (?) neck muscles.
  • None in response to saccades in the dark (!)
  • Over half have sensory responses.

GPe:

  • 2 types
    • HF, 70 Hz, interrupted with long pauses.
    • LF, 10 Hz, with frequent spontaneous bursts.
  • Activity during movement remarkably similar to GPi.
  • Weak encoding of movement amplitude, velocity, and muscle length and force is weak.
    • Movement related activity is late.
  • Might effect center - surround inhibition on the GPi; unclear what it does to the STN?

SNpc:

  • Schultz and Romo 1995 - SNpc neurons respond as early as possible to stimuli that indicates the availability of reward, and to the presence of reward, but only within a context.
    • No tuning to movement.

Synthesis:

  • Author believes that the basal ganglia serve to repress motor actions / plans that compete with the present or desired movement.
    • Eg. ones that are elicited through auto-association in the cerebral cortex.
    • corrolary: if there is an inability to focally inhibit competing mechanisms generally, it might be expected that the resulting movement deficit would be compounded during a sequence of movements, as is observed.
  • Discrete lesions in experimental animals often do not produce the movement disorders associated with human basal ganglia disease.
  • If the tonically active basal ganglia output inhibits competing motor mechanisms, the tonic inhibition must be removed from desired mechanisms. This must be done in a focused manner at the right time and in the right context in order not to activate competing mechanisms. The vast machinery of the striatum with its context-specificity, plasticity and spatiotemporal filtering selects which MPGs should be allowed to turn on. Thus, when a movement is made, the basal ganglia output has two parallel actions: inhibition of a multitude of competing MPGs via STN and GPi and focused selection of desired MPGs via striatum and GPi. Dysfunction of either of these actions would cause abnormal posture and movement.

Parkinson's disease:

  • Symptoms:
    • Tremor at rest
    • bradykinesia
    • paucity of movement (akinesia)
    • muscular rigidity
    • abnormally flexed posture with postural instability.
  • Tremor possibly from abnormal bursting in the thalamus. (Pare et al 1990)
  • Highly idiopathic and progressive.
  • Symptoms may reflect involvement of other systems in addition to the nigrostriatal dopamine system.
  • Bradykinesia:
    • excessive co-contraction, insufficient agonist activity.
    • movement is more impaired when visual cues are absent.
      • self-initiated movements are slower than visually cued movements
      • more impaired when deprived of visual feedback of the ongoing movement or if they cannot see the moving body.
      • Likely they have an increased dependence on visual feedback to compansate for the deficit.
    • slower on simultaneous and sequential movements than they were on individual components (Benecke et al 1986, 1987).
      • Greater latency to begin second movement.
      • Others have found no particular sequencing deficit (Agostino et al 1994).
  • Rigidity likely due to inability to inhibit reflex mechanisms.
    • One of these is the transcortical reflex, which can (normally) be inhibited when subjects are instructed not to resist movement.
      • PD patients have abnormally increased transcortical stretch reflexes.
      • Reflex cannot be inhibited upon instruction (Berardelli et al 1983, Rothwell et al 1983, Taton and Lee 1975).
    • When normal subjects are subjected to a perturbation in the anterior-posterior dimension while standing, they have a stereotyped pattern of muscle activity in the legs and trunk that maintains upright stance. If they then sit down and are subjected to the same perturbation, this activity no longer occurs. By contrast, patients with Parkinson’s disease have an inappropriate cocontraction of leg and back muscles in response to perturbation from upright stance. When the same subjects are subjected to a perturbation in a sitting position, they continue to have the same pattern of muscle activity. (Horak et al 1992)
  • Akinesia
    • May be due to a loss of of dopamine input to the prefrontal, premotor, or motor cortex. (Gaspar et al 1991, 1992; Sawaguchi and Goldman-Rakic 1994).
      • Animals with focal lesions to dopamine input to prefrontal cortex have prolonged reaction times (Humer et al 1994); animals with basal ganglia lesion do not.
  • Microwriting / micrographia: common problem where writing size is normal initially, but within several letters the writing gets progressively smaller so that by the end of the line, it may be illegible.
    • Hypothesis: depending on the movement and mechanisms involved, the number of mechanisms competing with the desired movement may increase additively as the sequence progresses leafing to progressive slowing of the movement.

Huntingtons

  • Early stages characterized by frequent, brief, random twitch-like movements and dementia. smoe of the movements resemble normal voluntary movement.
  • Involuntary EMG bursts 50 - 300 ms in duration.
  • Marked loss of striatal neurons.
    • Specifically, MSN enkephalin-containing that project to GPe. (Reiner 1988).
    • Substance-P MSN that project to GPi and SNr are preserved until later in the disease when rigidity typically appears.
    • Experimental lesions in the striatum rarely cause chorea, which makes sense as it is the specific pattern of striatal cell loss that matters (Crossman, 1987).
    • Stroke of the striatum in humans rarely causes chorea.
  • It should be emphasized that neurons in many parts of the brain including cortex and cerebellum degenerate in Huntington's disease, hence inferences of basal ganglia function drawn from HD must be interpreted with caution.
  • In contrast to PD, the long-latency stretch reflex is absent or reduced in Huntington's disease.
    • Plus somatosensory evoked potentials are markedly reduced.
    • People with chorea not from Huntington's disease have normal long-latency reflexes.

STN / Hemiballismus

  • Damage to STN by ischemic stroke results in bizarre involuntary movement that is charaterized by large amplitude, flinging (ballistic) movement of the contralateral extremities.
    • Symptoms are immediate and improve over time.
    • Similar to chorea, but more commonly affects proximal joints, and the movements are larger.
  • Hemiballismus can be caused by injecting biculculine into STN, which is somewhat paradoxical since biculculine is a GABA antagonist and would be expected to cause disinihbition (activation) of STN. Yet the results are similar to lesion of STN. (Crossman 1987)
  • After STN lesion there is decreased activity in GPe and GPi.
  • Hemiballismus can be eliminated by lesioning GPi outputs (Carpener 1950).
  • STN is exitatory in GPi / GPe; lesioning reduces GPi's ability to inhibit competing motor programs.
    • Loss of excitatory input to GPi results in abnormal phasic or bursting activity in GPi or its targets and this bursting causes twitches or chorea.

Experimental lesions:

  • Focal inactivation of the putamen with GABA-A agonist muscimol causes decreased movement amplitude with cocontraction of agonist and antagonist muscles in visually-guided arm movements.
  • Lesions studies suggest that the striatum is functionally heterogeneous with the function of each component determined by its cortical afferents.
    • Authors suggest that the function of each component is more likely to be reflected in its outputs than inputs.
  • Caudate does seem involved in more cognitive processing; it has different connectivity despite similar construction.
  • Muscimol into the SNr results in involuntary saccades and inability to mantain fixation.
    • Thus, just as GPi inactivation results in abnormal excess limb and trunk muscle activity, SNr inactivation results in abnormal excess eye movements. (Hikosaka and Wurtz, 1985b).
  • Lesion of GPi is an old treatment for PD in humans (Cooper and Bravo, 1958). \
    • Surprisingly, the most consistent beneficial effect of pallidotomy may be the reduction of dyskinesias that are induced by L-Dopa treatment (Laitinen et al 1992).

Large papers are not dissimilar from large software projects -- they take time, iteration, and concentration. Papers, however, are harder as the feedback is not immediate and gratifying.

____References____

[0] Mink JW, The basal ganglia: focused selection and inhibition of competing motor programs.Prog Neurobiol 50:4, 381-425 (1996 Nov)
[1] Flaherty AW, Graybiel AM, Input-output organization of the sensorimotor striatum in the squirrel monkey.J Neurosci 14:2, 599-610 (1994 Feb)
[2] Crutcher MD, DeLong MR, Single cell studies of the primate putamen. II. Relations to direction of movement and pattern of muscular activity.Exp Brain Res 53:2, 244-58 (1984)
[3] Wichmann T, Bergman H, DeLong MR, The primate subthalamic nucleus. I. Functional properties in intact animals.J Neurophysiol 72:2, 494-506 (1994 Aug)

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ref: -0 tags: delong georgoupolos basal ganglia DBS date: 03-05-2012 22:04 gmt revision:2 [1] [0] [head]

PMID-6389041 Functional organization of the basal ganglia: contributions of single-cell recording studies.

  • CAn't seem to find the paper ... these observations are from the abstract.
  • phasic changes in neural discharge in relation to movements of specific body parts (e.g. leg, arm, neck, face);
  • short-latency (sensory) neural responses to passive joint rotation;
  • a somatotopic organization of movement-related neurons in GPe, GPi, and STN;
  • a clustering of functionally similar neurons in the putamen and globus pallidus;
  • greater representation of the proximal than of the distal portion of the limb;
  • changes in neural activity in reaction-time tasks, suggesting a greater role of the basal ganglia in the execution than in the initiation of movement in this paradigm; a clear relation of neuronal activity to direction, amplitude (?velocity) of movement, and force;
  • a preferential relation of neural activity to the direction of movement, rather than to the pattern of muscular activity.
  • suggest that the basal ganglia may play a role in the control of movement parameters rather than (or independent of) the pattern of muscular activity.
  • The presence of somatotopic organization in the putamen and globus pallidus, together with known topographic striopallidal connections, suggests that segregated, parallel cortico-subcortical loops subserve 'motor' and 'complex' functions.

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ref: bookmark-3000 tags: DBS refs date: 03-05-2012 17:08 gmt revision:9 [8] [7] [6] [5] [4] [3] [head]

DBS refs (for translating from word to my latex-based build system):

  1. PMID-12450039 Abosch A, Hutchison WD, Saint-Cyr JA, Dostrovsky JO, Lozano AM (2002) Movement-related neurons of the subthalamic nucleus in patients with Parkinson disease. Journal of neurosurgery 97:1167-1172.
  2. PMID-2723733 Aertsen AM, Gerstein GL, Habib MK, Palm G (1989) Dynamics of neuronal firing correlation: modulation of "effective connectivity". Journal of neurophysiology 61:900-917.
  3. PMID-15601936 Amirnovin R, Williams ZM, Cosgrove GR, Eskandar EN (2004) Visually guided movements suppress subthalamic oscillations in Parkinson's disease patients. The Journal of neuroscience : the official journal of the Society for Neuroscience 24:11302-11306.
  4. PMID-18634849 Amtage F, Henschel K, Schelter B, Vesper J, Timmer J, Lucking CH, Hellwig B (2008) Tremor-correlated neuronal activity in the subthalamic nucleus of Parkinsonian patients. Neuroscience letters 442:195-199.
  5. PMID-9219885 Awiszus F (1997) Spike train analysis. Journal of neuroscience methods 74:155-166.
  6. PMID-11948769 Benazzouz A, Breit S, Koudsie A, Pollak P, Krack P, Benabid AL (2002) Intraoperative microrecordings of the subthalamic nucleus in Parkinson's disease. Movement disorders : official journal of the Movement Disorder Society 17 Suppl 3:S145-149.
  7. PMID-15255250 Brodkey JA, Tasker RR, Hamani C, McAndrews MP, Dostrovsky JO, Lozano AM (2004) Tremor cells in the human thalamus: differences among neurological disorders. Journal of neurosurgery 101:43-47.
  8. PMID-11863600 Davidsen J, Schuster HG (2002) Simple model for 1/f(alpha) noise. Physical review E, Statistical, nonlinear, and soft matter physics 65:026120.
  9. PMID-9827589 Deuschl G, Bain P, Brin M (1998) Consensus statement of the Movement Disorder Society on Tremor. Ad Hoc Scientific Committee. Movement disorders : official journal of the Movement Disorder Society 13 Suppl 3:2-23.
  10. PMID-16943402 Deuschl G et al. (2006) A randomized trial of deep-brain stimulation for Parkinson's disease. The New England journal of medicine 355:896-908.
  11. PMID-11685413 Ghazanfar AA, Krupa DJ, Nicolelis MA (2001) Role of cortical feedback in the receptive field structure and nonlinear response properties of somatosensory thalamic neurons. Experimental brain research Experimentelle Hirnforschung Experimentation cerebrale 141:88-100.
  12. PMID-12626014 Guillery RW, Sherman SM (2002) The thalamus as a monitor of motor outputs. Philosophical transactions of the Royal Society of London Series B, Biological sciences 357:1809-1821.
  13. PMID-16120664 Gutierrez R, Carmena JM, Nicolelis MA, Simon SA (2006) Orbitofrontal ensemble activity monitors licking and distinguishes among natural rewards. Journal of neurophysiology 95:119-133.
  14. PMID-15317839 Hua SE, Lenz FA (2005) Posture-related oscillations in human cerebellar thalamus in essential tremor are enabled by voluntary motor circuits. Journal of neurophysiology 93:117-127.
  15. PMID-9665587 {1020} Kennedy PR, Bakay RA (1998) Restoration of neural output from a paralyzed patient by a direct brain connection. Neuroreport 9:1707-1711.
  16. PMID-15473196 Kennedy PR, Kirby MT, Moore MM, King B, Mallory A (2004) Computer control using human intracortical local field potentials. IEEE transactions on neural systems and rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society 12:339-344.
  17. PMID-11391740 Koller WC, Lyons KE, Wilkinson SB, Troster AI, Pahwa R (2001) Long-term safety and efficacy of unilateral deep brain stimulation of the thalamus in essential tremor. Movement disorders : official journal of the Movement Disorder Society 16:464-468.
  18. PMID-14663050 Kumar R, Lozano AM, Sime E, Lang AE (2003) Long-term follow-up of thalamic deep brain stimulation for essential and parkinsonian tremor. Neurology 61:1601-1604.
  19. PMID-7823093 Lebedev MA, Denton JM, Nelson RJ (1994) Vibration-entrained and premovement activity in monkey primary somatosensory cortex. Journal of neurophysiology 72:1654-1673.
  20. PMID-21779720 Lebedev MA, Tate AJ, Hanson TL, Li Z, O'Doherty JE, Winans JA, Ifft PJ, Zhuang KZ, Fitzsimmons NA, Schwarz DA, Fuller AM, An JH, Nicolelis MA (2011) Future developments in brain-machine interface research. Clinics (Sao Paulo) 66 Suppl 1:25-32.
  21. PMID-11929926 see {1099}
  22. PMID-2276045 Lenz FA, Kwan HC, Dostrovsky JO, Tasker RR, Murphy JT, Lenz YE (1990) Single unit analysis of the human ventral thalamic nuclear group. Activity correlated with movement. Brain : a journal of neurology 113 ( Pt 6):1795-1821.
  23. PMID-8032863 Lenz FA, Kwan HC, Martin RL, Tasker RR, Dostrovsky JO, Lenz YE (1994) Single unit analysis of the human ventral thalamic nuclear group. Tremor-related activity in functionally identified cells. Brain : a journal of neurology 117 ( Pt 3):531-543.
  24. PMID-3346719 Lenz FA, Tasker RR, Kwan HC, Schnider S, Kwong R, Murayama Y, Dostrovsky JO, Murphy JT (1988) Single unit analysis of the human ventral thalamic nuclear group: correlation of thalamic "tremor cells" with the 3-6 Hz component of parkinsonian tremor. The Journal of neuroscience : the official journal of the Society for Neuroscience 8:754-764.
  25. PMID-11027240 Levy R, Hutchison WD, Lozano AM, Dostrovsky JO (2000) High-frequency synchronization of neuronal activity in the subthalamic nucleus of parkinsonian patients with limb tremor. The Journal of neuroscience : the official journal of the Society for Neuroscience 20:7766-7775.
  26. PMID-12023310 see {829} Levy R, Ashby P, Hutchison WD, Lang AE, Lozano AM, Dostrovsky JO (2002) Dependence of subthalamic nucleus oscillations on movement and dopamine in Parkinson's disease. Brain : a journal of neurology 125:1196-1209.
  27. PMID-10947834 Magarinos-Ascone CM, Figueiras-Mendez R, Riva-Meana C, Cordoba-Fernandez A (2000) Subthalamic neuron activity related to tremor and movement in Parkinson's disease. The European journal of neuroscience 12:2597-2607.
  28. PMID-10717435 Magnin M, Morel A, Jeanmonod D (2000) Single-unit analysis of the pallidum, thalamus and subthalamic nucleus in parkinsonian patients. Neuroscience 96:549-564.
  29. PMID-11157565 Marsden JF, Limousin-Dowsey P, Ashby P, Pollak P, Brown P (2001) Subthalamic nucleus, sensorimotor cortex and muscle interrelationships in Parkinson's disease. Brain : a journal of neurology 124:378-388.
  30. PMID-11201755 Nicolelis MA (2001) Actions from thoughts. Nature 409:403-407.
  31. PMID-19543222 Nicolelis MA, Lebedev MA (2009) Principles of neural ensemble physiology underlying the operation of brain-machine interfaces. Nature reviews Neuroscience 10:530-540.
  32. PMID-9781530 Ondo W, Jankovic J, Schwartz K, Almaguer M, Simpson RK (1998) Unilateral thalamic deep brain stimulation for refractory essential tremor and Parkinson's disease tremor. Neurology 51:1063-1069.
  33. PMID-7711765 see {1091} Parent A, Hazrati LN (1995) Functional anatomy of the basal ganglia. II. The place of subthalamic nucleus and external pallidum in basal ganglia circuitry. Brain research Brain research reviews 20:128-154.
  34. PMID-18164493 Patil PG, Turner DA (2008) The development of brain-machine interface neuroprosthetic devices. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 5:137-146.
  35. PMID-15214971 Patil PG, Carmena JM, Nicolelis MA, Turner DA (2004) Ensemble recordings of human subcortical neurons as a source of motor control signals for a brain-machine interface. Neurosurgery 55:27-35; discussion 35-28.
  36. PMID-15973409 Quiroga RQ, Reddy L, Kreiman G, Koch C, Fried I (2005) Invariant visual representation by single neurons in the human brain. Nature 435:1102-1107.
  37. PMID-10197761 Raeva S, Vainberg N, Tikhonov Y, Tsetlin I (1999) Analysis of evoked activity patterns of human thalamic ventrolateral neurons during verbally ordered voluntary movements. Neuroscience 88:377-392.
  38. PMID-11522580 Rodriguez-Oroz MC, Rodriguez M, Guridi J, Mewes K, Chockkman V, Vitek J, DeLong MR, Obeso JA (2001) The subthalamic nucleus in Parkinson's disease: somatotopic organization and physiological characteristics. Brain : a journal of neurology 124:1777-1790.
  39. PMID-15975946 see {1120}-8 Rodriguez-Oroz MC et al. (2005) Bilateral deep brain stimulation in Parkinson's disease: a multicentre study with 4 years follow-up. Brain : a journal of neurology 128:2240-2249.
  40. PMID-12815658 Theodosopoulos PV, Marks WJ, Jr., Christine C, Starr PA (2003) Locations of movement-related cells in the human subthalamic nucleus in Parkinson's disease. Movement disorders : official journal of the Movement Disorder Society 18:791-798.
  41. PMID-16160097 Ventura V, Cai C, Kass RE (2005a) Statistical assessment of time-varying dependency between two neurons. Journal of neurophysiology 94:2940-2947.
  42. PMID-16160096 Ventura V, Cai C, Kass RE (2005b) Trial-to-trial variability and its effect on time-varying dependency between two neurons. Journal of neurophysiology 94:2928-2939.
  43. PMID-15563555 Wiest MC, Bentley N, Nicolelis MA (2005) Heterogeneous integration of bilateral whisker signals by neurons in primary somatosensory cortex of awake rats. Journal of neurophysiology 93:2966-2973.
  44. PMID-15635456 Williams ZM, Neimat JS, Cosgrove GR, Eskandar EN (2005) Timing and direction selectivity of subthalamic and pallidal neurons in patients with Parkinson disease. Experimental brain research Experimentelle Hirnforschung Experimentation cerebrale 162:407-416.
  45. PMID-9466402 Zirh TA, Lenz FA, Reich SG, Dougherty PM (1998) Patterns of bursting occurring in thalamic cells during parkinsonian tremor. Neuroscience 83:107-121.

  1. bibtex:Batschelet Batschelet E (1981) Circular statistics in biology. London ; New York: Academic Press.
  2. {318} Carmena JM, Lebedev MA, Crist RE, O'Doherty JE, Santucci DM, Dimitrov DF, Patil PG, Henriquez CS, Nicolelis MA (2003) Learning to control a brain-machine interface for reaching and grasping by primates. PLoS biology 1:E42.
  3. {690} Chapin JK, Moxon KA, Markowitz RS, Nicolelis MA (1999) Real-time control of a robot arm using simultaneously recorded neurons in the motor cortex. Nature neuroscience 2:664-670.
  4. {329} Fetz EE (2007) Volitional control of neural activity: implications for brain-computer interfaces. The Journal of physiology 579:571-579.
  5. {943} Fuentes R, Petersson P, Siesser WB, Caron MG, Nicolelis MA (2009) Spinal cord stimulation restores locomotion in animal models of Parkinson's disease. Science 323:1578-1582.
  6. {711} Gradinaru V, Mogri M, Thompson KR, Henderson JM, Deisseroth K (2009) Optical deconstruction of parkinsonian neural circuitry. Science 324:354-359.
  7. {268} Kennedy PR, Bakay RA, Moore MM, Adams K, Goldwaithe J (2000) Direct control of a computer from the human central nervous system. IEEE transactions on rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society 8:198-202.
  8. bibtex:Kuiper Kuiper NH (1962) Tests concerning random points on a circle. Proc Kon Ned Akad Wetensch 63:38-47.
  9. {934} Lebedev MA, Nicolelis MA (2006) Brain-machine interfaces: past, present and future. Trends in neurosciences 29:536-546.
  10. bibtex:Oppenheim Oppenheim AV, Schafer RW (1975) Digital signal processing. Englewood Cliffs, N.J.,: Prentice-Hall.
  11. {317} Wessberg J, Stambaugh CR, Kralik JD, Beck PD, Laubach M, Chapin JK, Kim J, Biggs SJ, Srinivasan MA, Nicolelis MA (2000) Real-time prediction of hand trajectory by ensembles of cortical neurons in primates. Nature 408:361-365.
  12. bibtex:Zar Zar JH (1999) Biostatistical analysis, 4th Edition. Upper Saddle River, N.J.: Prentice Hall.

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ref: Weinberger-2009.09 tags: empty date: 03-05-2012 16:33 gmt revision:4 [3] [2] [1] [0] [head]

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ref: Weinberger-2009.09 tags: STN DBS PD oscillations beta band review date: 03-05-2012 16:32 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-19460368[0] Pathological subthalamic nucleus oscillations in PD: can they be the cause of bradykinesia and akinesia?

  • Review of {1075}
  • Suppression of beta-band is correlated with the improvement in combined measures of bradykinesia and rigidity.
    • This does not mean that the oscillations cause rigidity! only that L-DOPA affects both. Focused entirely on Beta band.
  • Previously shown that the degree of beta oscillatory activity in the STN of PD patients correlates with the patients' benefit from dopaminergic medications, but not with baseline motor deficits. (the treatment but not the symptoms)
  • Levy 2000, 2001 for the existence of oscillatory activity in the STN & globus pallidus.
  • Prominent beta band activity in GPi & STN LFP. [Levy 2000, Levy 2001 , Brown 2001]
  • Short train HFS of the STN has been shown to decrease STN-cortex coherence for up to 25s after application. [Wingeier 2006] [Kuhn 2008]
    • Others disagree. [Foffani et al., 2006] and [Rossi et al., 2008] ).
  • In a response task, decrease in beta-band activity negatively correlates with reaction time. [Kuhn 2004]
    • Beta suppression is also correlated with increased motor planning [Williams 2005]
  • Beta band activity also present in healthy monkey striatum, human putamen, and cortex. (I wonder how? many references.)
  • Yet, to date there is no clear evidence that the degree of synchronization in the beta band directly accounts for the motor deficits in PD.
  • It has been recently shown that the percentage of neurons exhibiting oscillatory firing in the beta range correlates well (r squared = 0.62) with the degree by which PD motor symptoms improved after dopamine replacement therapy (Weinberger et al. 2006 PMID-17005611)
  • It should be noted that decrease in beta-band activity may be caused by -- rather than causal of -- decreased akinesia and rigidity.
    • That said, in rats treated with 6-OHDA, an increase in beta band activity took several days to appear after drug administration, and appeared at the same time as clinical symptoms.
  • Interesting! Activity-dependent plasticity was remarkably enhanced with a low dose of levodopa in the basal ganglia output of SNr and that there was a surprisingly good correlation (r squared = 0.81) between symptoms and the level of synaptic plasticity (Prescott et al., 2009) [2].
  • Other theory: exaggerated synchrony in the basal ganglia limits the ability to encode meaningful information, as all neurons are entrained to the same frequency hence undifferentiated.
    • Thought beta band may just be a non-coding resting state. Synaptic plasticity goes awry, and all neurons become entrained. Explains bradykinesia but not rigidity.

____References____

[0] Weinberger M, Hutchison WD, Dostrovsky JO, Pathological subthalamic nucleus oscillations in PD: can they be the cause of bradykinesia and akinesia?Exp Neurol 219:1, 58-61 (2009 Sep)
[1] Kühn AA, Tsui A, Aziz T, Ray N, Brücke C, Kupsch A, Schneider GH, Brown P, Pathological synchronisation in the subthalamic nucleus of patients with Parkinson's disease relates to both bradykinesia and rigidity.Exp Neurol 215:2, 380-7 (2009 Feb)
[2] Prescott IA, Dostrovsky JO, Moro E, Hodaie M, Lozano AM, Hutchison WD, Levodopa enhances synaptic plasticity in the substantia nigra pars reticulata of Parkinson's disease patients.Brain 132:Pt 2, 309-18 (2009 Feb)

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ref: -0 tags: empty date: 03-03-2012 02:47 gmt revision:1 [0] [head]

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ref: Fuentes-2009.03 tags: Nicoelis DCS spinal cord stimulation PD Fuentes Petersson 6-OHDA date: 03-03-2012 02:46 gmt revision:3 [2] [1] [0] [head]

PMID-19299613[0] Spinal cord stimulation restores locomotion in animal models of Parkinson's disease.

  • Motivation: different levels of cortical oscillation during movement and rest (LFO decreased, medium-high freq increased); PD associated with abnormal synchronous corticostriatal oscillations.
  • In epilepsy patients, stimulation of peripheral nerve afferents is effective in desychronizing low-frequency neural activity, reducing the frequency and duration of seizures (8,9,10) PMID-11050139[1] PMID-16886985[2] PMID-18188148[3]
  • DCS (dorsal column stimulation)
    • Epidural, longitudal electrodes, horizontal electrical field.
    • Upper thoracic, mice.
    • 300Hz.
    • simpler and safer than brain surgery.
    • [24] DCS induces no increase in arousal. (Wall, PD. Brain 1970; 93:505.
  • used the tyrosine hydroxyalse inhibitor AMPT
  • M1 LFP: Osc around 1.5-4Hz and 10-15Hz enhanced; osc > 25Hz subdued.
  • DCS increased locomotion by 29x in depleted animals, and 4.9x in normal animals.
  • Also titrated L-DOPA with DAT-KO mice. Without dopamine, there is no movement.
    • DCS increased L-DOPA effectiveness by 5x (1/5 the dose was required)
  • Verified in a 6-OHDA lesion model in rats.
    • Lesioned animals moved more, sham moved less.
  • Activation of locomotion is via striatal medium spiny neurons projecting to the output nuclei of the basal ganglia [26 PMID-8402406[4] ,27 PMID-1695404[5]].
  • In PD, with reduced striatal dopamine levels, the activation threshold of the projection neurons from the striatum is significantly increased [25] PMID-17916382[6].

____References____

[0] Fuentes R, Petersson P, Siesser WB, Caron MG, Nicolelis MA, Spinal cord stimulation restores locomotion in animal models of Parkinson's disease.Science 323:5921, 1578-82 (2009 Mar 20)
[1] Fanselow EE, Reid AP, Nicolelis MA, Reduction of pentylenetetrazole-induced seizure activity in awake rats by seizure-triggered trigeminal nerve stimulation.J Neurosci 20:21, 8160-8 (2000 Nov 1)
[2] DeGiorgio CM, Shewmon A, Murray D, Whitehurst T, Pilot study of trigeminal nerve stimulation (TNS) for epilepsy: a proof-of-concept trial.Epilepsia 47:7, 1213-5 (2006 Jul)
[3] George MS, Nahas Z, Bohning DE, Lomarev M, Denslow S, Osenbach R, Ballenger JC, Vagus nerve stimulation: a new form of therapeutic brain stimulation.CNS Spectr 5:11, 43-52 (2000 Nov)
[4] Brudzynski SM, Wu M, Mogenson GJ, Decreases in rat locomotor activity as a result of changes in synaptic transmission to neurons within the mesencephalic locomotor region.Can J Physiol Pharmacol 71:5-6, 394-406 (1993 May-Jun)
[5] DeLong MR, Primate models of movement disorders of basal ganglia origin.Trends Neurosci 13:7, 281-5 (1990 Jul)
[6] Grillner S, Wallén P, Saitoh K, Kozlov A, Robertson B, Neural bases of goal-directed locomotion in vertebrates--an overview.Brain Res Rev 57:1, 2-12 (2008 Jan)

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ref: Plaha-2008.05 tags: zona incerta DBS date: 03-03-2012 01:45 gmt revision:4 [3] [2] [1] [0] [head]

PMID-18037630[0] Bilateral stimulation in the caudal zona incerta nucleus for tremor control

  • VL DBS does not always work, and patients may develop tolerance; tried instead the caudal Zona Incerta (cZI).
    • VL ~= VIM (?) -- differing thalamic naming nomenclatures -- see {1100}.
    • VL does not always work for proximal tremor.
  • nice results! Resting PD tremor improved by 94.8% and postural tremor by 88.2%. The total tremor score improved by 75.9% in 6 patients with ET
    • Works for both distal and proximal tremor.
  • Original finding: PMID-18671648
  • nice figure therein.

____References____

[0] Plaha P, Khan S, Gill SS, Bilateral stimulation of the caudal zona incerta nucleus for tremor control.J Neurol Neurosurg Psychiatry 79:5, 504-13 (2008 May)

{1120}
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ref: Pollak-2002.01 tags: Benabid DBS VIM date: 03-02-2012 22:20 gmt revision:12 [11] [10] [9] [8] [7] [6] [head]

Relevant papers:

  • 1 PMID-11948771[0] Intraoperative micro- and macrostimulation of the subthalamic nucleus in Parkinson's disease.
    • Suggest using microelectrodes for precise mapping of suitable target area.
  • 2 PMID-11948758[1] Mechanisms of deep brain stimulation.
    • The mechanism could be either one or a combination of several causes: jamming of a feedback loop, activation of inhibitory structures included in a more complex network, blockade of membrane ion channels, deplorisation blockade, synaptic exhaustion, induction of early genes, changes in local blood flow, neuroplasticity. (I think that it's likely some sort of information block, since it's so immediately efficacious).
    • Emphasis on neuroplasticity.
  • 3 PMID-9400514[2] Stimulation of subthalamic nucleus alleviates tremor in Parkinson's disease.
    • Stimulation of the ventral intermediate nucleus of the thalamus (Vim) greatly improves tremor in 88% of patients with PD, but rigidity is only moderately improved and akinesia is not improved.
    • In patients with tremor-dominated PD, STN stimulation should be preferred to Vim stimulation since most of these patients will develop disabling akinesia not improved by Vim stimulation.
  • 4 PMID-7631092[3] Acute and long-term effects of subthalamic nucleus stimulation in Parkinson's disease.
    • The final position of the chronic electrodes was optimized using electrophysiological recording and stimulation along with clinical assessment and surface EMG of agonist and antagonist muscles of the examined limbs.
    • things have not changed much since then - 130 Hz, quadripolar medtronic electrode, electrophysiological and stereotaxic guidance.
    • no dyskinesia or hemiballismus observed.
  • 5 PMID-8235208[4] [Effects of the stimulation of the subthalamic nucleus in Parkinson disease].
    • same as above, but in French, and first.
  • 6 PMID-19081516[5] Deep brain stimulation of the subthalamic nucleus for the treatment of Parkinson's disease.
    • Side effects are mainly neurocognitive, with side-effects created by spread of stimulation to surrounding structures, depending on the precise location of electrodes.
    • Little pressure to optimize in the present system.
    • Needs to be extended to developing countries, too.
  • 7 PMID-17960811[6] Lifetime of Itrel II pulse generators for subthalamic nucleus stimulation in Parkinson's disease.
    • They last 83 +- 14 months -- wow!
    • Replace the device when the battery gets low. duh.
  • 8 PMID-15975946[7] Bilateral deep brain stimulation in Parkinson's disease: a multicentre study with 4 years follow-up.
    • DBS to the STN is effective.
      • assessed 3-4 years relative to baseline, UPDRS-III score.
      • Good mobility wityhout dyskinesias, better activities of daily living.
    • side effects: cognitive decline, speech difficulty, instability, gait disorders and depression.
  • 9 PMID-15040711[8] Deep brain stimulation of the subthalamic nucleus in Parkinson's disease 1993-2003: where are we 10 years on?
    • Efficacy still somewhat not clear.
    • STN improves motor function by at least 60% (!), and reduces the levodopa requirement.
    • Reviews some pathophysiology & basic science.

VIM:

  • 10 PMID-15197715[9] Partial lesion of thalamic ventral intermediate nucleus after chronic high-frequency stimulation.
    • 60% cell loss within 0.5mm of the electrode tip.
    • still, tremor improvement attributable to chronic stimulation, not microthalamotomy.
  • 11 PMID-8592222[10] Chronic electrical stimulation of the ventralis intermedius nucleus of the thalamus as a treatment of movement disorders.
    • Ventralis intermedius stimulation has since been used by the authors over the last 8 years as a treatment in 117 patients with movement disorders (80 cases of Parkinson's disease, 20 cases of essential tremor, and 17 cases of various dyskinesias and dystonias including four multiple sclerosis)
    • Chronic VIM stimulation, which is reversible, adaptable, and well tolerated even by patients undergoing bilateral surgery (74 of 117 patients) and by elderly patients, should replace thalamotomy in the regular surgical treatment of parkinsonian and essential tremors.
  • 12 PMID-8748831[11] Stimulation of the ventral intermediate thalamic nucleus in tremor dominated Parkinson's disease and essential tremor.
    • LFS of VIM increases tremor, whereas HFS decreases it.
  • 13 PMID-8453462[12] Thalamic stimulation and suppression of parkinsonian tremor. Evidence of a cerebellar deactivation using positron emission tomography.
    • The suppression of tremor was specifically associated with a decrease of rCBF (PET) in the cerebellum, whereas the ineffective stimulation induced a decrease of rCBF in ipsilateral cerebral cortex.
  • 14 PMID-8420163[13] Long-term effects of chronic stimulation of the ventral intermediate thalamic nucleus in different types of tremor.
    • folow up.
    • HFS to the VIM in 26 PD, 6 ET patients.
    • Of the 43 thalami stimulated, 27 showed complete relief from tremor and 11 major improvement (88%).
    • Much better than thalamotomy.
  • 15 PMID-1671433[14] Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus.
    • same as above, but with abstract. 1991 -- original.

Stem cells / Gene therapy:

  • 16 PMID-16902198[15] Functional neuronal differentiation of bone marrow-derived mesenchymal stem cells.
    • cells express markers for neurons (shape, NF-L beta-tubulin.
    • cells can differentiate along the neural pathway.
    • but how will they migrate properly? hum, need a review on this.
  • 17 PMID-21087733[16] Gene therapy for Parkinson's disease: do we have the cure?
    • Levodopa dyskinesias occur 5-10 years after treatment start and decrease the benefit of treatment.
    • Levodopa does not alter the course of PD.
    • Neural grafts for PD have been in development for three decades now, yet they are still considered experimental as they have not provided therapeutic benefit.
    • Marks and colleagues report results of the first double-blind phase 2 trial for gene therapy of PD.
      • This involves growth factors, retrogradely transported from the striatum to the SNpc.
      • only saw effect at 18 months -- may have taken a long time for the gene to be expressed?
    • Gene therapy can cure. DBS cannot.
    • need to test with dopa-radiography PET scans.
    • might cause cancer.
    • See [17][18][19][20][21]

Non-dbs:

  • PMID-12725785[22] An unsupervised automatic method for sorting neuronal spike waveforms in awake and freely moving animals.
  • PMID-19882716[23] Neuroprotection of midbrain dopaminergic cells in MPTP-treated mice after near-infrared light treatment.

____References____

[0] Pollak P, Krack P, Fraix V, Mendes A, Moro E, Chabardes S, Benabid AL, Intraoperative micro- and macrostimulation of the subthalamic nucleus in Parkinson's disease.Mov Disord 17 Suppl 3no Issue S155-61 (2002)
[1] Benabid AL, Benazzous A, Pollak P, Mechanisms of deep brain stimulation.Mov Disord 17 Suppl 3no Issue S73-4 (2002)
[2] Krack P, Pollak P, Limousin P, Benazzouz A, Benabid AL, Stimulation of subthalamic nucleus alleviates tremor in Parkinson's disease.Lancet 350:9092, 1675 (1997 Dec 6)
[3] Benabid AL, Pollak P, Gross C, Hoffmann D, Benazzouz A, Gao DM, Laurent A, Gentil M, Perret J, Acute and long-term effects of subthalamic nucleus stimulation in Parkinson's disease.Stereotact Funct Neurosurg 62:1-4, 76-84 (1994)
[4] Pollak P, Benabid AL, Gross C, Gao DM, Laurent A, Benazzouz A, Hoffmann D, Gentil M, Perret J, [Effects of the stimulation of the subthalamic nucleus in Parkinson disease].Rev Neurol (Paris) 149:3, 175-6 (1993)
[5] Benabid AL, Chabardes S, Mitrofanis J, Pollak P, Deep brain stimulation of the subthalamic nucleus for the treatment of Parkinson's disease.Lancet Neurol 8:1, 67-81 (2009 Jan)
[6] Anheim M, Fraix V, Chabardès S, Krack P, Benabid AL, Pollak P, Lifetime of Itrel II pulse generators for subthalamic nucleus stimulation in Parkinson's disease.Mov Disord 22:16, 2436-9 (2007 Dec)
[7] Rodriguez-Oroz MC, Obeso JA, Lang AE, Houeto JL, Pollak P, Rehncrona S, Kulisevsky J, Albanese A, Volkmann J, Hariz MI, Quinn NP, Speelman JD, Guridi J, Zamarbide I, Gironell A, Molet J, Pascual-Sedano B, Pidoux B, Bonnet AM, Agid Y, Xie J, Benabid AL, Lozano AM, Saint-Cyr J, Romito L, Contarino MF, Scerrati M, Fraix V, Van Blercom N, Bilateral deep brain stimulation in Parkinson's disease: a multicentre study with 4 years follow-up.Brain 128:Pt 10, 2240-9 (2005 Oct)
[8] Ashkan K, Wallace B, Bell BA, Benabid AL, Deep brain stimulation of the subthalamic nucleus in Parkinson's disease 1993-2003: where are we 10 years on?Br J Neurosurg 18:1, 19-34 (2004 Feb)
[9] Henderson J, Rodriguez M, O'Sullivan D, Pell M, Fung V, Benabid AL, Halliday G, Partial lesion of thalamic ventral intermediate nucleus after chronic high-frequency stimulation.Mov Disord 19:6, 709-11 (2004 Jun)
[10] Benabid AL, Pollak P, Gao D, Hoffmann D, Limousin P, Gay E, Payen I, Benazzouz A, Chronic electrical stimulation of the ventralis intermedius nucleus of the thalamus as a treatment of movement disorders.J Neurosurg 84:2, 203-14 (1996 Feb)
[11] Alesch F, Pinter MM, Helscher RJ, Fertl L, Benabid AL, Koos WT, Stimulation of the ventral intermediate thalamic nucleus in tremor dominated Parkinson's disease and essential tremor.Acta Neurochir (Wien) 136:1-2, 75-81 (1995)
[12] Deiber MP, Pollak P, Passingham R, Landais P, Gervason C, Cinotti L, Friston K, Frackowiak R, Mauguière F, Benabid AL, Thalamic stimulation and suppression of parkinsonian tremor. Evidence of a cerebellar deactivation using positron emission tomography.Brain 116 ( Pt 1)no Issue 267-79 (1993 Feb)
[13] Pollak P, Benabid AL, Gervason CL, Hoffmann D, Seigneuret E, Perret J, Long-term effects of chronic stimulation of the ventral intermediate thalamic nucleus in different types of tremor.Adv Neurol 60no Issue 408-13 (1993)
[14] Benabid AL, Pollak P, Gervason C, Hoffmann D, Gao DM, Hommel M, Perret JE, de Rougemont J, Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus.Lancet 337:8738, 403-6 (1991 Feb 16)
[15] Tropel P, Platet N, Platel JC, Noël D, Albrieux M, Benabid AL, Berger F, Functional neuronal differentiation of bone marrow-derived mesenchymal stem cells.Stem Cells 24:12, 2868-76 (2006 Dec)
[16] Benabid AL, Gene therapy for Parkinson's disease: do we have the cure?Lancet Neurol 9:12, 1142-3 (2010 Dec)
[17] Marks WJ Jr, Bartus RT, Siffert J, Davis CS, Lozano A, Boulis N, Vitek J, Stacy M, Turner D, Verhagen L, Bakay R, Watts R, Guthrie B, Jankovic J, Simpson R, Tagliati M, Alterman R, Stern M, Baltuch G, Starr PA, Larson PS, Ostrem JL, Nutt J, Kieburtz K, Kordower JH, Olanow CW, Gene delivery of AAV2-neurturin for Parkinson's disease: a double-blind, randomised, controlled trial.Lancet Neurol 9:12, 1164-72 (2010 Dec)
[18] Herzog CD, Dass B, Holden JE, Stansell J 3rd, Gasmi M, Tuszynski MH, Bartus RT, Kordower JH, Striatal delivery of CERE-120, an AAV2 vector encoding human neurturin, enhances activity of the dopaminergic nigrostriatal system in aged monkeys.Mov Disord 22:8, 1124-32 (2007 Jun 15)
[19] Kordower JH, Herzog CD, Dass B, Bakay RA, Stansell J 3rd, Gasmi M, Bartus RT, Delivery of neurturin by AAV2 (CERE-120)-mediated gene transfer provides structural and functional neuroprotection and neurorestoration in MPTP-treated monkeys.Ann Neurol 60:6, 706-15 (2006 Dec)
[20] Kordower JH, Emborg ME, Bloch J, Ma SY, Chu Y, Leventhal L, McBride J, Chen EY, Palfi S, Roitberg BZ, Brown WD, Holden JE, Pyzalski R, Taylor MD, Carvey P, Ling Z, Trono D, Hantraye P, Déglon N, Aebischer P, Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson's disease.Science 290:5492, 767-73 (2000 Oct 27)
[21] Eslamboli A, Georgievska B, Ridley RM, Baker HF, Muzyczka N, Burger C, Mandel RJ, Annett L, Kirik D, Continuous low-level glial cell line-derived neurotrophic factor delivery using recombinant adeno-associated viral vectors provides neuroprotection and induces behavioral recovery in a primate model of Parkinson's disease.J Neurosci 25:4, 769-77 (2005 Jan 26)
[22] Aksenova TI, Chibirova OK, Dryga OA, Tetko IV, Benabid AL, Villa AE, An unsupervised automatic method for sorting neuronal spike waveforms in awake and freely moving animals.Methods 30:2, 178-87 (2003 Jun)
[23] Shaw VE, Spana S, Ashkan K, Benabid AL, Stone J, Baker GE, Mitrofanis J, Neuroprotection of midbrain dopaminergic cells in MPTP-treated mice after near-infrared light treatment.J Comp Neurol 518:1, 25-40 (2010 Jan 1)

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ref: Penney-1983.01 tags: DBS parkinsons model review chorea review date: 03-02-2012 21:22 gmt revision:2 [1] [0] [head]

PMID-6838141[0] Speculations on the Functional Anatomy of Basal Ganglia Disorders

  • "We present a model based on the accumulating evidence that suggests the importance of a cortico-striato-pallido-thalamocortical feedback circuit as the major extrapyramidal influcence on the motor system in man.
    • Behaviors generated from the cerebral cortex are focused and facilitated by projections through the basal ganglia.
    • The chorea of Huntington's disease and the bradykineasia of PD are opposite extremes of the dysfunction of this system.
      • Huntington's: inability to supress unwanted movements.
      • Inadequate inhibitory modulation of ongoing movement by the nigrostriatal dopamine pathway.
  • Anatomy already described in Kemp & Powell 1971. More details have accrued in the subsequent 4 decades.
  • Kinner Wilson 1929 -- astute observations on the nature of chorea, in Huntington's and others: how they appear to be purposeful, but are objectviely not. He infers that it may be a disorder of the premotor cortex, since the primary cortex seems to control individual muscle contractions. Much data supports this now.
  • All dopamine agonists result in choreiform dyskinesias.
  • Tardive dyskinesia seems to result from drug-induced striatal dopamine receptor supersensitivity after long-term high-dose neuroleptic therapy also manifests choreaform movements.
  • In huntington's disease, supersensitive GABA receptors develop in the globus pallidus following striatal deinnervation.
    • Likewise for PD: supersensitive dopamine receptors develop in the striatum (Lee at al 1978).
  • mention neuromodulators (substance P, angiotensin II, cholecystokinin, leucine-enkephalin) which have been largely ignored in later work -- why?
  • Tremor is very responsive to muscarinic cholinergic agonists, hence striatal cholinergic neurons may play a role in the etiology of tremor.
    • Or the effect could be mediated through the cortex (my observation).
    • But then again this is inconsistent with the fact that pallidotomy is effective at mediating tremor in PD patients.
    • Tremor is unusual in diseases like Hallervorden-Spatz and other pallidal degenerations presumably because pallidothalamic pathways are necessary for the manifestation of PD tremor.
  • THe descending SNr pathways to the tectum and midbrain tegmentum appear to be responsible for the rotatory behavior seen in models of parkinsonism in the rat (Morelli et al 1981).
    • Rotatory behavior exhibited by rats after lesioning of nigral dopamine neurons continues even in the absence of the telencephalon and thalamus (Papadopolous and Huston 1981).

Got some things completely wrong:

  • Say that the cells of the subthalamic nucleus are inhibitory on the cells of MGP (GPi)/SNr

____References____

[0] Penney JB Jr, Young AB, Speculations on the functional anatomy of basal ganglia disorders.Annu Rev Neurosci 6no Issue 73-94 (1983)

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ref: Costa-2006.1 tags: Rui Costa Miguel Nicolelis Dopamine depletion excess cortex striatum hyperkinesia akinesia parkinsons DAT-KO date: 03-02-2012 01:03 gmt revision:8 [7] [6] [5] [4] [3] [2] [head]

PMID-17046697 Rapid alterations in corticostriatal ensemble coordination during acute dopamine-dependent motor dysfunction.

  • used rats where they could rapidly switch between dopamine depletion (0.2%) and overexpression (500%)
  • most cortical and striatal neurons ( approximately 70%) changed firing rate during the transition between dopamine-related hyperkinesia and akinesia,
    • buuut the overall cortical firing rate remained unchanged
  • repeated dopamine depletion is accompanied by the loss of glutamergic synapses in striatopallidal neurons (Day et al 2006) PMID-16415865 (Kaneda et al 2005). PMID-16367790
  • with Marc Caron
  • Dopamine is believed to modulate positively the direct striatal pathway that contains predominantly D1-type receptors and disinhibits cortical neurons to modulate negatively the indirect pathway that predominantly contains D2-type receptors and increased crotical inhibition (Albin et al 1989 {1050}, Filion and Tremblay 1991; Gerfen 1992, Parr-Brownlie and Hyland, 2005).
  • According to the classical view (Albin et al 1989), lack of DA release should lead to inhibition of cortical activity and an inability to produce movement, while an excess of Dopamine should lead to increased cortical activity and hyperactivity (Gerfen, 1992).
    • mouse model: DDD PMID-17030735[] (dopamine transporter knockout)

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ref: -0 tags: Albin basal ganglia dopamine 1989 parkinsons huntingtons hemiballismus date: 03-02-2012 00:28 gmt revision:1 [0] [head]

PMID-2479133 The functional anatomy of basal ganglia disorders.

  • Matrix neurons mainly containing substance P mainly project upon the GPi or SNr
    • while those containing enkephalins project on the GPe.
  • Striosome neurons projecting to the SNc contain mainly substance P.
  • Classical hypothesis:
  • Hyperkinetic disorders, which are characterized by an excess of abnormal movements, are postulated to result from the selective impairment of striatal neurons projecting to the lateral globus pallidus.
    • These are suppressed by D2 receptor antagonists & exacerbated by dopamine agonists.
    • Chorea is a primary example.
    • Despite Huntingtons, traumatic, ischemic, or ablative lesions of the striatum in man or animals rarely produces chorea or atheosis (writhing movements).
    • In HD, cholinergic agonists will alleviate choreoatheosis, while anti-cholinergic drugs exacerbate it.
  • Hypokinetic disorders, such as Parkinson's disease, are hypothesized to result from a complex series of changes in the activity of striatal projection neuron subpopulations resulting in an increase in basal ganglia output.
    • opposite of HD, exacerbated by D2 antagonists and ameliorated by DA agonists, as well as anti-cholinergics.
  • Dystonia = the spontaneous assumption of unusual fixed postures lasting from seconds to minutes.

  • Standard model suggests that striatal lesions should result in spontaneous movements, while this is not the case in man or other mammals. (less inhibition on GPi / SNr -> greater susceptibility of the thalamus to competing programs (?))
  • hyperkinetic movements can be produced by infusing bicululline, a GABA receptor antagonist, into GPe -- silencing it.
  • In early HD, when chorea is most prominent, there is a selective loss of striatal neurons projecting to the LGP (enkephalin staining).
    • Substance P containing neurons are lost later in the disease.
  • Administration of D2 antagonists increases the synthesis of enkephalins and pre-proenkephalin mRNA in the striatum.
    • This presumably represents increases in neuronal activity.
    • Inhibition of GPe neurons decreases hyperkinetic movements? But STN is excitatory? This does not add up.
  • Hemiballismus may be caused by disinhibition of SNr (?) and the VA/VL/MD/CM-Pf thalamocortical projections.

Saccades:

  • In both PD and HD, there are both increases in the latency of initiation of saccades, slowing of saccadic velocity, and interruption of saccades.
    • In HD, there is an early loss of substance-P containing striatal terminals in the SNr, possibly resulting in over-inhibition of tectal neurons.
    • HD patients cannot supress saccades to flashed stimulus.
    • No abnormalities in saccadic control in tourette's syndrome.
  • Hikosaka: suggest that caudate neurons involved in the initiation of saccades are part of a mechanism in which sensory data are evaluated in the context of learned behaviors and anticipated actions, and then used to initiate behavior.

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ref: -0 tags: locomotion decerebrated monkeys spinal cord section STN stimulation date: 03-01-2012 23:53 gmt revision:0 [head]

PMID-7326562 Locomotor control in macaque monkeys

  • Were not able to induce walking with in monkeys with a sectioned spinal cord
  • Were able to induce walking motion by pulsed stimulation of the STN, with varying walking speed with varying currents!
  • Detailed, informative report, more than I have time to record here today.

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ref: Prescott-2006.01 tags: basal_ganglia action selection motor control robot date: 03-01-2012 17:56 gmt revision:4 [3] [2] [1] [0] [head]

PMID-16153803[0] The robot basal ganglia: action selection by an embedded model of the basal ganglia

  • they implemented a model of the basal ganglia in a robot. The model switches between competing (hypothetical) actions based on input salience. There are only a possible actions in their robot.
  • they reiterate the common conception that the basal ganglia are implicated in action selection: what to do next ( also mentioned are other functions - perception and cognition working memory and many other aspects of motor function. )
  • huh, interesting : cognitive psychologists have discovered that when an observable system has more than three interacting parts, it becomes very difficult for human minds to predict accurately how that system will change over time. (!!!) I dig disclaimers like this.
    • therefore, very limited understanding can be gleaned from informal, box and arrow style models.
      • I think the same is true of many biological analysis - including analysis of the immune and nervous systems - it needs to be at a much higher level of quantification
    • they also say that a model must be validated by placing it within the entire behavioral system.
  • the basal ganglia seem to be suitable for switching between competing channels & providing the required clean selection of a winner.
    • (1) striatal cells have up and down states, and can only switch between them with heavy coincident inputs.
    • (2) selective local inhibition between channels.
    • (3) dopamine innervation D1 = exitation; D2 = inhibition. I never really got how this enters their model; figure 1 seems like it would describe it, but it needs more math :)
    • (4) feedforward off-center, on surround network. they ref some other work..
      • I still don't feel like their explanation is the best (they use kinda wishy-washy terms) - though it is a step in the right direction.
  • people with schizophrenia sometimes switch cognitive focus rapidly; schizo is though to be due to a dopamine imbalance. Same problem with ADD.
    • treatment for ADD: amphetamine (blocks monoamine transporter, increases extracellular concentration of DA), ritalin. Both allow for heightened concentration: once you select a task, you stick with 'it' (the thought / prediction pathway) for longer. Dopamine is definintely involved in action selection, duhh.
    • their model supports this behavior: If the tonic dopamine level is very low, the robot has difficulty initiating actions; if the DA level is high, then it tends to select more than one action at the same time. (wait.. this implies that DA is too high in people with ADD? what? perhaps this is a consequence of the two different types of DA receptors? )
  • (...) basal ganglia - thalamo-cotrical loops my act to provide a positive feedback pathway that can maintain appropriate level of salience to selected behavior.
  • much of the input to the basal ganglia comprises collateral fibers from motor regions that project to the spinal cord and brainstem structures.
    • activity changes in the BG occur slightly after the beginning of EMG activity (good evidence!) Such signals may be important for controlling the maintenance and termination of selected behavior.

My thoughts:

  • what if the STN is involved in controlling the stability of neuronal activity - that is, preventing motor feedback instability by knocking down the gain. (whereas the cerebellum is involved in the balance and coordination interpretations of stability)
    • Normally, the human motor system is very stable, but when you lack dopamine innervation, you both cannot move (become very rigid) & have tremor (an inability to control cyclical oscillations).
      • That is, perhaps oscillation is due to a intrinsic inability to modulate gain.
      • more likely it is a manifestation/symptom of pathological activity in the control loop.

____References____

[0] Prescott TJ, Montes González FM, Gurney K, Humphries MD, Redgrave P, A robot model of the basal ganglia: behavior and intrinsic processing.Neural Netw 19:1, 31-61 (2006 Jan)

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ref: Litvak-2011.02 tags: DBS MEG STN synchrony oscillations london connectivity beta basal ganglia date: 02-29-2012 19:59 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

PMID-21147836[0] Resting oscillatory cortico-subthalamic connectivity in patients with Parkinson’s disease

  • Used MEG plus LFP recordings of the STN.
  • Two spatially and spectrally separated networks were identified.
    • A temporoparietal-brainstem network was coherent with the subthalamic nucleus in the alpha (7-13 Hz) band,
    • whilst a predominantly frontal network was coherent in the beta (15-35 Hz) band.
  • Dopaminergic medication modulated the resting beta network, by increasing beta coherence between the subthalamic region and prefrontal cortex.
  • Idea of characterizing connectivity based on synchronization / comodulation: (Fries 2005).
  • Synchronization is exaggerated in Parkinson's disease (Sharott et al 2005b, Mallet et al 2008).
  • Some patients had dopamine dysregulation syndrome and medication-induced hypersexuality.
  • None of the > 45 Hz STN LFP patterns had a scalp pattern consistent with a cortical source.
  • Cortical source frequency not really that different between ON and OFF medication, except at maybe tremor frequencies.
  • But cortex drives the subthalamic area robustly.
    • That said, these patients were at rest.
    • Small difference between ON and OFF states possibly because they were at rest.
  • Both healthy subjects and those with parkinson's disease show resting connectivity between basal ganglia and the SMA, temporopareital area and parts of the prefrontal cortex. (Postuma and Dagher 2006); Helmich et al 2010).
  • Beta band coupling between cerebral cortex and subthalamic nucleus drops before and during movement (Cassidy et al 2002 PMID-12023312; Lalo et al 2008)
    • During imagination of movement (Kuhn et al 2008).
    • During action observation (Alegre et al 2010).
      • Is this consistent with the conflict / reinforcement learning hypothesis?
  • A big problem is determining if the oscillations are pathological or non-pathological
    • Impossible to control, since we cannot record from healthy humans.

____References____

[0] Litvak V, Jha A, Eusebio A, Oostenveld R, Foltynie T, Limousin P, Zrinzo L, Hariz MI, Friston K, Brown P, Resting oscillatory cortico-subthalamic connectivity in patients with Parkinson's disease.Brain 134:Pt 2, 359-74 (2011 Feb)

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ref: Iansek-1980.04 tags: globus pallidus GPe GPi electrophysiology 1980 date: 02-29-2012 18:17 gmt revision:2 [1] [0] [head]

PMID-7411442 The monkey globus pallidus: neuronal discharge properties in relation to movement.

  • motor units are generally inactive during inactivity. the relationship to movement of the discharges of such neurons was found to be very specific
    • This is in comparison to other results, which report a sustained firing, esp in GPi.
  • the discharges (as analyzed through histograms) of many neurones were related to only a particular direction of movement about one joint in the right limb.
  • some discharges were related to multijoint movements -> probably due to control of contraction of particular muscles.
    • nonetheless, this relationship was a loose one; there is not a tight coupling between pallidal activity and muscle contraction.
  • some responded to ipsilateral as well as contralateral movements.
    • PMID-7925805 Unilateral leasions in the GP results in bilateral increase in reaction time. hence, GP is involved in initiation. RT speed eventually recovered.
  • only the posterior globus pallidus - well posterior to the maximum expansion - contained movement related cells.
    • the a-p stereotaxic coordinates were less useful than the location of the maximum mediolateral width of the structure.
    • cells occurred in clusters, separated by regoins of non-movement related.
  • cells in the internal segment had no such organization.
  • many of the non-movement related neurons were tonically active.
  • this was before there was A/D recording, apparently!

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ref: -0 tags: bilateral STN lesion rats perseverence nose poke impulsivity DBS basal ganglia date: 02-29-2012 17:44 gmt revision:1 [0] [head]

PMID-9421169 Bilateral lesions of the subthalamic nucleus induce multiple deficits in an attentional task in rats.

  • Excitotoxic lesion of STN alleviate motor impairment found in PD dopamine depletion model.
  • What about normal rats?
  • investigated the behavioural effects of bilateral excitotoxic lesions of the STN in rats performing a five-choice test of divided and sustained visual attention, modelled on the human continuous performance task.
  • This task required the animals to detect a brief visual stimulus presented in one of five possible locations and respond by a nose-poke in this illuminated hole within a fixed delay, for food reinforcement
  • STN lesion:
    • decreased discriminatory activity
    • increase premature responses & preservative panel pushes and nose-poke responses.
  • Subsequent D1/D2 anatagonist administration reduced premature responses but not preservative nose-pokes.
  • Consistent with action selection and inhibition.
  • Suggest that these cognitive-type effects should be examined in humand that have STN DBS.

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ref: -0 tags: distrupted oscillations Mallet 2008 6-OHDA globus pallidus date: 02-29-2012 01:15 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-19109506 Parkinsonian beta oscillations in the external globus pallidus and their relationship with subthalamic nucleus activity.

  • Rat 6-OHDA.
  • On rate model: Although synchronization of GP unit activity increased by almost 100-fold during beta oscillations, the mean firing rate of GP neurons decreased compared with controls.
  • Synchronized firing persisted across different brain states, suggesting hardwiring.
  • GP and STN are frequency aligned but phase skewed.
    • Lateral inhibition in GP seems essential / see model.
  • Suggest that GPe / STN could generate oscillations that propagate to the rest of the BG.
    • But then why is the cortex required?

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ref: Mallet-2008.04 tags: DBS oscillations STN beta 6-OHDA rats ECoG acute date: 02-29-2012 01:11 gmt revision:4 [3] [2] [1] [0] [head]

PMID-18448656[0] Disrupted dopamine transmission and the emergence of exaggerated beta oscillations in subthalamic nucleus and cerebral cortex.

  • STN has pronounced beta band oscillations in PD patients.
  • 6-OHDA rodent model (here) shows the same, depending on state.
    • Synchronization in both local cellular assemblies and broadly across the STN + ECoG.
    • ECoG looks causal in their studies.
    • Frequencies > 15 Hz, not lower (theta), as in other studies.
  • Excessively synchronized beta oscillations reduce the information coding capacity of STN neuronal ensembles, which may contribute to parkinsonian motor impairment.
  • Acute disruption of dopamine transmission in control animals with antagonists of D(1)/D(2) receptors did not exaggerate STN or cortical beta oscillations.
    • This despite the potent agonist induced catalepsy in the rats!
    • Must be neural plasticity & structural.
    • Takes > 4 days.
    • Actual striatal DA levels decrease within 1 h of midbrain 6-OHDA
  • Under normal conditions, beta synchronization may be useful for sensory-motor processing (Uhlhaas and Singer 2006).
  • Synchronized activity is preferentially transmitted due to temporal summation.

____References____

[0] Mallet N, Pogosyan A, Sharott A, Csicsvari J, Bolam JP, Brown P, Magill PJ, Disrupted dopamine transmission and the emergence of exaggerated beta oscillations in subthalamic nucleus and cerebral cortex.J Neurosci 28:18, 4795-806 (2008 Apr 30)

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ref: Timmermann-2003.01 tags: DBS double tremor oscillations DICS beamforming parkinsons date: 02-29-2012 00:39 gmt revision:4 [3] [2] [1] [0] [head]

PMID-12477707[0] The cerebral oscillatory network of parkinsonian resting tremor.

  • Patients had idiopathic unliateral tremor-dominated PD.
  • MEG + EMG -> coherence analysis. (+ DICS for deep MEG recording).
  • M1 correlated to EMG at tremor and double-tremor frequency following medication withdrawal overnight.
    • M1 leads by 15 - 25 ms, consistent with conduction delay.
  • Unlike other studies, they find that many cortical areas are also coherent / oscillating with M1, including:
    • Cingulate and supplementary motor area (CMA / SMA)
    • Lateral premotor cortex (PM).
    • SII
    • Posterior pareital cortex PPC
    • contralateral cerebellum - strongest at double frequency.
  • In contrast, the cerebellum, SMA/CMA and PM show little evidence for direct coupling with the peripheral EMG but seem to be connected with the periphery via other cerebral areas (e.g. M1)
  • Power spectral analysis of activity in all central areas indicated the strongest frequency coherence at double tremor frequency.
    • Especially cerebro-cerebro coupling.
  • These open-ended observation studies are useful!

____References____

[0] Timmermann L, Gross J, Dirks M, Volkmann J, Freund HJ, Schnitzler A, The cerebral oscillatory network of parkinsonian resting tremor.Brain 126:Pt 1, 199-212 (2003 Jan)

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ref: Bergman-1990.09 tags: parkinsons STN lesion 1990 MPTP DBS date: 02-28-2012 21:06 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

PMID-2402638[] Reversal of experimental parkinsonism by lesions of the subthalamic nucleus.

  • MPTP monkeys.
  • Guided by the rate hypothesis (which is probably false, but no matter!)
  • The lesions reduced all of the major motor disturbances in the contralateral limbs, including akinesia, rigidity, and tremor.
  • the study that opened up a treatment - and helped many people!!
  • wasn't the first DBS surgery done in 1983 by Benabid? No, it was 1993!

____References____

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ref: -0 tags: dopamine reinforcement learning funneling reduction basal ganglia striatum DBS date: 02-28-2012 01:29 gmt revision:2 [1] [0] [head]

PMID-15242667 Anatomical funneling, sparse connectivity and redundancy reduction in the neural networks of the basal ganglia

  • Major attributes of the BG:
    • Numerical reduction in the number of neurons across layers of the 'feed forward' (wrong!) network,
    • lateral inhibitory connections within the layers
    • modulatory effects of dopamine and acetylcholine.
  • Stochastic decision making task in monkeys.
  • Dopamine and ACh deliver different messages. DA much more specific.
  • Output nuclei of BG show uncorrelated activity.
    • THey see this as a means of compression -- more likely it is a training signal.
  • Striatum:
    • each striatal projection neuron receives 5300 cortico-striatal synapses; the dendritic fields of same contains 4e5 axons.
    • Say that a typical striatal neuron is spherical (?).
    • Striatal dendritic tree is very dense, whereas pallidal dendritic tree is sparse, with 4 main and 13 tips.
    • A striatal axon provides 240 synapses in the pallidum and makes 10 contacts with one pallidal neuron on average.
  • I don't necessarily disagree with the information-compression hypothesis, but I don't disagree either.
    • Learning seems a more likely hypothesis; could be that we fail to see many effects due to the transient nature of the signals, but I cannot do a thorough literature search on this.

PMID-15233923 Coincident but distinct messages of midbrain dopamine and striatal tonically active neurons.

  • Same task as above.
  • both ACh (putatively, TANs in this study) and DA neurons respond to reward related events.
  • dopamine neurons' response reflects mismatch between expectation and outcome in the positive domain
  • TANs are invariant to reward predictability.
  • TANs are synchronized; most DA neurons are not.
  • Striatum displays the densest staining in the CNS for dopamine (Lavoie et al 1989) and ACh (Holt et al 1997)
    • Depression of striatal acetylcholine can be used to treat PD (Pisani et al 2003).
    • Might be a DA/ ACh balance problem (Barbeau 1962).
  • Deficit of either DA or ACh has been shown to disrupt reward-related learning processes. (Kitabatake et al 2003, Matsumoto 1999, Knowlton et al 1996).
  • Upon reward, dopaminergic neurons increase firing rate, whereas ACh neurons pause.
  • Primates show overshoot -- for a probabalistic relative reward, they saturate anything above 0.8 probability to 1. Rats and pigeons do not show this effect (figure 2 F).

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ref: Wichmann-1994.08 tags: STN normal physiology delong wichmann date: 02-27-2012 22:05 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-7983514[0] The Primate Subthalamic Nucleus. 1. Functional Properties in Intact Animals.

  • Lots of cells -- 301 cells in the STN, 1589 microstimulation sites, 72 cross-correlation pairs.
  • 55% modulated to passive contralateral movement, 86% of these to muscle palpitation, 25% to light touch.
  • Caudalventral STN devoid of calls responding to touch or movement.
  • Somatotopic organization: lateral arm, medial leg.
    • Representation of proximal muscles / portions much larger than distal portions, consistent with Carpenter 1950.
  • Mostly rate increases in response to step tracking tasks, usually uniphasic.
  • 40ua, 200-500 ms train duration, 400 Hz did not produce movement. Stimulation of the lateral borders often led to eye movements.
  • 11% of pairs were seen to be synchronized, separated by 100-200um.
    • Much smaller than in the cortex.
    • This strongly supports the concept of functional segregation in the basal ganglia-thalamocortical pathways.
  • Mean firing rate 23 Hz old studies, 19 Hz present study.
  • "Most hypotheses concerning the role of the basal ganglia in movement were derived from experience with diseases originating in the basal ganglia or from experiments involving the activation or inactivation of large parts of BG nuclei. These results are notoriously hard to interpret, because gross changes in motor circuit activity likely results in rather nonspecific activity changes in multiple parts of the neuraxis, unlike minute alterations in the firing patterns of individual neurons in the basal ganglia may have under physiological conditions".
  • Basal ganglia may have a role in the late phases of movement, perhaps even their termination.
  • "More is known about the role of the indirect pathway in the pathophysiology of movement disorders such as Parkinson's disease and ballism than in the control of normal movement." word, yes.

____References____

[0] Wichmann T, Bergman H, DeLong MR, The primate subthalamic nucleus. I. Functional properties in intact animals.J Neurophysiol 72:2, 494-506 (1994 Aug)

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ref: -0 tags: DBS dopamine synaptic plasticity striatum date: 02-27-2012 21:57 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

PMID-11285003 Dopaminergic control of synaptic plasticity in the dorsal striatum.

  • Repetitive stimulation of corticostriatal fibers causes a massive release of glutamate and DA in the striatum, and depending on the glutamate receptor subtype preferentially activated, produces either long-term depression (LTD) or long-term potentiation (LTP) of excitatory synaptic transmission.
  • D1 and D2 (like) receptors interact synergistically to allow LTD formation, and in opposition while inducing LTP.
  • Stimulation of DA receptors has been shown to modulate voltage-dependent conductances in striatal spiny neurons, but it does not cause depolarization or hyperpolarization (Calabresi et al 2000a PMID-11052221; Nicola et al 2000)
  • Striatal spiny neurons present a high degree of colocalization of subtypes of DA and glutamate receptors. PMID-9215599
  • Striatal cells have up and down states. Wilson and Kawaguchi 1996 PMID-8601819
  • Both LTD and LTP are induced in the striatum by the repetitive stimulation of corticostriatal fibers.
    • Repetition is associated with the dramatic increase of both glutamate and DA in the striatum. (presynaptic?)
  • LTP is enhanced by blocking or removing D2 receptors.
  • More complexity here - in terms of receptors and blocking. (sure magnesium blocks NMDA receptors, but there are many other drugs used...)

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ref: -0 tags: parent collateralization basal ganglia date: 02-24-2012 22:00 gmt revision:0 [head]

PMID-11052216 Organization of the basal ganglia: the importance of axonal collateralization.

  • "...revealed the presence of various types of projection neurons with profusely collateralized axons within each of the major components of the basal ganglia. Such findings call for a reappraisal of current concepts of the anatomical and functional organization of the basal ganglia, which play such a crucial role in the control of motor behavior. "

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ref: DeLong-1985.02 tags: globus pallidus subthalamic STN electrophysiology Georgopoulos DeLong DBS date: 02-24-2012 21:50 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-3981228[0] Primate globus pallidus and subthalamic nucleus: functional organization

  • cells respond to arm, leg, and orofacial movements (mostly in the arm tho)
  • ~25% of these responded to passive joint movement - the latency is in accord with proprioceptive driving.
  • arm-related neurons were found throughout the rostrocaudal extent of both globus pallidus segments
  • look @ the articles that cite this!

____References____

[0] DeLong MR, Crutcher MD, Georgopoulos AP, Primate globus pallidus and subthalamic nucleus: functional organization.J Neurophysiol 53:2, 530-43 (1985 Feb)

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ref: -0 tags: globus pallidus delong response tuning date: 02-24-2012 21:41 gmt revision:1 [0] [head]

PMID-4997823 Activity of Pallidal Neurons During Movement

  • GPe activity notably different from GPi.
    • "So characteristic were the discharge patterns of units in each segment that early in the course of the experiment ti be came apparent when the electrode entered and left each segment.
  • Two types of cells in GPe:
    • High frequency with periods of quiet (85%)
    • Low frequency with bursts.
  • Only one type in GPi: continuous HF discharge, 10-100 Hz, mean 63 Hz.
  • Mostly contralateral, ~ 15% ipsilateral related discharge.
  • Leg and arm responding units intermixed.
  • Conclusion: pallidus not involved in reflexes.
  • Substantia innominata = region posterior the pallidus, contains the nucleus basalis.
  • I'd really like to get recordings of this quality!

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ref: -0 tags: dopamine reward prediction striatum error striatum orbitofrontal reward date: 02-24-2012 21:26 gmt revision:1 [0] [head]

PMID-11105648 Involvement of basal ganglia and orbitofrontal cortex in goal-directed behavior.

  • Many regions have a complex set of activations, but dopamine neurons appear more homogenous: they report the error in reward prediction.
    • "The homogeneity of responsiveness across the population of dopamine neurons indicates that this error signal is widely broadcast to dopamine terminal regions where it could provide a teaching signal for synaptic modifications underlying the learning of goal-directed appetitive behaviors."
    • Signals are not contingent on the type of behavior needed to obtain the reward, and hence represent a relatively 'pure' reward prediction error.
  • Unlike dopamine neurons, many striatal neurons respond to predicted rewards, although at least some may reflect the relative degree of predictability in the magnitude of the responses to reward.
  • Neuronal activations in the orbitofrontal cortex appear to involve less integration of behavioral and reward-related information, but rather incorporate another aspect of reward, the relative motivational significance of different rewards.
  • Processing is hierarchical (or supposed to be so):
    • Dopamine neurons provide a relatively pure signal of an error in reward prediction,
    • Striatal neurons signal not only reward, but also behavioral contingencies,
    • Orbitofrontal neurons signal reward and incorporate relative reward preference.

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ref: -0 tags: putamen functional organization basal ganglia date: 02-24-2012 21:01 gmt revision:0 [head]

PMID-6705861 Single cell studies of the primate putamen. I. Functional organization.

  • Cells in the striatum have very low levels of activity -- some are simply not spontaneously active.
  • Other cells are tonically active at 3-6Hz (cholinergic?)
  • ( Most cells related to the direction of movement, not necessarily force.
  • Two types of load reactions: short latency (presumably sensory) and long-latency (motor -- related to the active return movement of the arm.)
  • Timing suggests that the striatum does not play a role in the earliest phases of movement, consistent with cooling studies, kainic acid lesions, or microstimulation. Only 19% of neurons were active before movement.
  • Many neurons were reactive to both active and passive movements in the same joint / direction.
    • The BG receive afferents from joint and not muscle receptors.

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ref: -0 tags: Romo basal ganglia movement control date: 02-24-2012 19:50 gmt revision:2 [1] [0] [head]

PMID-1483512 Role of the primate basal ganglia and frontal cortex in the internal generation of movements. I. Preparatory activity in the anterior striatum

  • Recorded from the head of the audate and rostral putamen.
  • Both spontaneous and cued / delayed-reward tasks.
  • Observed responses:
    • transient responses to cue, (2x as many to 'go' as 'nogo' cues)
    • sustained activity preceding the trigger stimulus or movement onset
      • Often this was ramp-like, indicating some sort of preparatory activity.
      • This could last 2-35 seconds, depending on the task, with a maximum of 80 s.
  • Premovement activity began 0.5-5.0s before movement onset (median 1 second).
    • Unrelated to saccadic eye movements.
    • 2/3 of these neurons were active only in spontaneous movements, and not in cued movements.
    • This is similar to activity in the frontal cortex; hence both are involved in preparing actions.

PMID-1483513 Role of primate basal ganglia and frontal cortex in the internal generation of movements. II. Movement-related activity in the anterior striatum.

  • Same experiments and recordings as above.
  • Time-locked responses to trigger, 60ms latency, independent of modality.
  • 44 neurons increased their activity before earlier EMG
  • 55 were activated with the movement,
  • 50 neurons were activated after movement onset.
  • I'm not entirely sure how this is different from above. (?)

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ref: -0 tags: striatum microstimulation abnormal myclonus dyskinesia date: 02-24-2012 19:44 gmt revision:0 [head]

PMID-21508304 Discontinuous Long-Train Stimulation in the Anterior Striatum in Monkeys Induces Abnormal Behavioral States

  • Long-train microstimulation induces complex, abnormal behavior: finger licking and biting, dyskinesias, grooming; more anterior (associative) resulted in hyper, hypo manic or stereotyped behaviors.
  • Short-train stimulation induces myoclonic-like movements.

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ref: Hershey-2010.12 tags: DBS impulsivity STN feedback stability gonogo date: 02-22-2012 22:04 gmt revision:8 [7] [6] [5] [4] [3] [2] [head]

PMID-20855421[0] Mapping Go-No-Go performance within the subthalamic nucleus region.

  • Support the dorsal-ventral motor-cognitive model.
  • Only ventral subthalamic stimulation effected Go-No-Go accuracy.
    • Both ventral and dorsal stimulation showed positive motor effects.
  • On inhibition in the STN: (Aron and Poldrack 2006; Frank et al 2007).
    • Thought: if methamphetamine and L-Dopa have similar impulsivity / punding / hobbyism effects, why do they think that the function is localized exclusively in the STN? These behaviors seem a more general problem of dopamine disregulation. Meth heads presumably have intact STN. The pausing hypothesis (e.g. STN controls pausing in conflict situations) seems better to me (maybe); have to check rat results.
    • Such is the problem with taking one thing out of a feedback loop and assuming the resultant deficit corresponds with the original 'function' insofar as one can be assigned. Think if you adjust the coefficients on a filter -- it gets all F'ed, with minor projection onto the frequency response.
    • Low-order systems are less sensitive to drastic parameter adjustment, but still purpose is obscured in feedback systems.
    • See {1082}
  • STN DBS can lead to impaired withholding strong prepotent responses with strong response conflict
    • Such as the Stroop task (Jahanshahi et al 2000; Schroeder et al 2002; Witt et al 2004)
    • Stop signal task (Ray et al 2009)
    • Go-nogo tasks (Hershey et al 2004; Ballanger et al 2009).
    • Rats show the same deficit in inhibiting responses in strong conflict cases (Baunex et al 1995, 2001; Baunez and Robbins 1997).
  • Suggest that significant variability in treatment responses could be from the exact location of stimulation.
    • Ventral STN closer to SNr, and dorsal is closer to the ZI and thalamus.

____References____

[0] Hershey T, Campbell MC, Videen TO, Lugar HM, Weaver PM, Hartlein J, Karimi M, Tabbal SD, Perlmutter JS, Mapping Go-No-Go performance within the subthalamic nucleus region.Brain 133:Pt 12, 3625-34 (2010 Dec)

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ref: Carpenter-1981.11 tags: STN subthalamic nucleus anatomy tracing globus_pallidus PPN substantia_nigra DBS date: 02-22-2012 22:01 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

PMID-7284825[0] Connections of the subthalamic nucleus in the monkey.

  • STN projects to both segments of the globus pallidus in a laminar and organized fashion.
    • most fibers projected to the lateral pallidal segment (aka GPe).
  • also projected to specific thalamic nuclei (VAmc, VLm, DMpl).
  • the major projection of PPN is to SN.
  • striatum projects to the substantia nigra pars reticulata (SNr). interesting.
  • see also: PMID-1707079[1]
    • "Anterograde transport in fibers and terminal fields surrounded retrogradely labeled cells in the LPS (GPe), suggesting a reciprocal relationship [to the STN]"
  • These data suggest that the STN receives its major subcortical input from cell of the LPS (GPe) arranged in arrays which have a rostrocaudal organization.
  • No cells of the MPS (GPi) or SN project to the STN.
  • The output of the STN is to both segments of the GP and SNpr.
  • Major subcortical projections to PPN arise from the MPS (GPi) and SNpr (output of the BG) , but afferents also arise from other sources.
    • The major projection of PPN is to SN.
    • HRP injected into PPN produced profuse retrograde transport in cells of the MPS and SNpr and distinct label in a few cells of the zona incerta and STN.

____References____

[0] Carpenter MB, Carleton SC, Keller JT, Conte P, Connections of the subthalamic nucleus in the monkey.Brain Res 224:1, 1-29 (1981 Nov 9)
[1] Carpenter MB, Jayaraman A, Subthalamic nucleus of the monkey: connections and immunocytochemical features of afferents.J Hirnforsch 31:5, 653-68 (1990)

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ref: Boulet-2006.1 tags: hemiballismus PD parkinsons STN subtalamic DBS dyskinesia rats 2006 glutamate date: 02-22-2012 18:58 gmt revision:1 [0] [head]

PMID-17050715 Subthalamic Stimulation-Induced Forelimb Dyskinesias Are Linked to an Increase in Glutamate Levels in the Substantia Nigra Pars Reticulata

  • STN-HFS-induced forelimb dyskinesia was blocked by microinjection of the Glu receptor antagonist kynurenate into the SNr and facilitated by microinjection of a mixture of the Glu receptor agonists AMPA and NMDA into the SNr.
    • Well, that just makes sense. STN is excitatory, GPi is an output structure of the BG, and stimulation should activate the area.

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ref: Bergman-1998.01 tags: basal ganglia globus pallidus electrophysiology parkinsons 2001 DBS date: 02-22-2012 18:52 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-9464684[0] Physiological aspects of information processing in the basal ganglia of normal and parkinsonian primates.

  • The firing of neurons in the globus pallidus of normal monkeys is almost always uncorrelated.
  • after MPTP treatment, the firing patterns of GP became correlated and oscillatory (see the figures!!)
  • dopamine must support normal segregation of the informational channels in the basal ganglia, and breakdown of this causes the pathology of PD.
  • has a decent diagram of the basal ganglia-thalamo-cortical circuits.
  • two different hypotheses of BG function: segregated and convergent. data support the former.

____References____

[0] Bergman H, Feingold A, Nini A, Raz A, Slovin H, Abeles M, Vaadia E, Physiological aspects of information processing in the basal ganglia of normal and parkinsonian primates.Trends Neurosci 21:1, 32-8 (1998 Jan)

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ref: Carlson-2010.02 tags: DBS PD STN lesion date: 02-22-2012 18:44 gmt revision:4 [3] [2] [1] [0] [head]

PMID-19955287[0] Deep brain stimulation does not silence neurons in subthalamic nucleus in Parkinson's patients.

  • word to that. not a functional lesion!
  • Record SUA during DBS of the STN. good idea.
  • Saw postpulse inhibition of 1-2 us 6 us after stim in 10 of the 14 analyzed
    • might be pulse locked spikes .. but could not see them.
  • predominant shift toward random firing.
  • DBS parameters: 3-5V, 80-200 Hz, 90-200us pulses, 33 neurons 11 patients.
  • DBS likely functions through white-matter activation to effect changes in neuronal activity throughout the BG - thalamus-cortex network.
  • Looked at the spaces between stimulus artifact.
  • nice figures.
  • DBS did not change mean firing rate.
  • Modeling studies suggest that DBS depolarizes myelinated fibers, without evoking or inhibiting discharges in local cell bodies (McIntyre et al 2004 ab PMID-14668299, Miocinovic et al 2006).
    • From the former: Suprathreshold stimulation caused suppression of intrinsic firing in the soma, but generated efferent output at the stimulus frequency in the axon.

____References____

[0] Carlson JD, Cleary DR, Cetas JS, Heinricher MM, Burchiel KJ, Deep brain stimulation does not silence neurons in subthalamic nucleus in Parkinson's patients.J Neurophysiol 103:2, 962-7 (2010 Feb)

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ref: Steigerwald-2008.11 tags: parkinsons disease essential tremor DBS STN VIM date: 02-22-2012 18:40 gmt revision:4 [3] [2] [1] [0] [head]

PMID-18701754[0] Neuronal activity of the human subthalamic nucleus in the parkinsonian and nonparkinsonian state

  • Recorded from the STN in both PD and ET patients -- with the ET patients acting as a control (sorta; as good as we'll get).
  • ET is common neuromotor condition that involves intention tremor and movement overshoot; progresses over many years.
    • Malfunction of the olivocerebellar pathways.
    • no involvement of Dopamine-dependent pathways.
  • 65 PD patients!
  • Classified single units based on ISI & the asymmetry index, the ratio of the mode to the mean of the ISI histogram.
    • bursting or burstlike firing, intermitten grouped firing separated by periods of pauses.
      • Further analyzed for burstlike features via 'burst surprise method' Salcman 1985).
    • irregular, broad ISI CV > 85.
    • Regular tonic firing, bell shaped ISI, CV < 90.
  • PD patients had more burst-like neurons; ET patients had more irregular neurons.
  • Neurons with theta and beta characteristics predominated in bursting neurons (71/81); gamma oscillationgs were commonly found in nonbursting cells (8/11).
  • Only found synchronized beta activity in SUAs recorded from PD patients.
  • Levy: emphasized the importance of tremor for beta-band oscillations because the majority of synchronous cells were recorded from five patients with resting tremor in the operating room, whereas no synchronous pairs were found in nontremulous patients.
  • aha! a limitation of our study, however, is the lack of tremor recordings during surgeries // we were therefore not able to determine the amount of tremor-locked activity within the 3-10 Hz or transient changes in response to intermittent tremor.
    • Another limitation: no movements, attention could have wandered.
  • Still, STN firing rate increased, as per MPTP model.
  • Shift toward bursting type activity in PD.
  • Did not find differences in the proportion of neurons exhibiting intrinsic oscillatory activity or interneuronal synchronization.
  • Large proportion of neurons exhibiting theta-band activity around 4Hz in PD patients; c.f. monkeys, 10 Hz activity dominates.
    • Tremor is not an accurate reporter of pathology.

____References____

[0] Steigerwald F, Pötter M, Herzog J, Pinsker M, Kopper F, Mehdorn H, Deuschl G, Volkmann J, Neuronal activity of the human subthalamic nucleus in the parkinsonian and nonparkinsonian state.J Neurophysiol 100:5, 2515-24 (2008 Nov)

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ref: Vitek-2008.03 tags: DBS function efferent STN date: 02-22-2012 18:39 gmt revision:2 [1] [0] [head]

PMID-18540149[0] Deep brain stimulation: how does it work?

  • MPTP monkey research suggests that activation of output and the resultant change in pattern of neuronal activity that permeates throughout the basal ganglia motor circuit is the mechanism responsible for symptom improvement.
    • Sensible network approach.
  • If pathological plasticity mechanisms are responsible for the symptoms, perhaps we should look for similarly slow treatments?

____References____

[0] Vitek JL, Deep brain stimulation: how does it work?Cleve Clin J Med 75 Suppl 2no Issue S59-65 (2008 Mar)

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ref: Holgado-2010.09 tags: DBS oscillations beta globus pallidus simulation computational model date: 02-22-2012 18:36 gmt revision:4 [3] [2] [1] [0] [head]

PMID-20844130[0] Conditions for the Generation of Beta Oscillations in the Subthalamic Nucleus–Globus Pallidus Network

  • Modeled the globus pallidus external & STN; arrived at criteria in which the system shows beta-band oscillations.
    • STN is primarily glutamergic and projects to GPe (along with many other areas..)
      • STN gets lots of cortical afferent, too.
    • GPe is GABAergic and projects profusely back to STN.
    • This inhibition leads to more accurate choices.
      • (Frank, 2006 PMID:,
        • The present [neural network] model incorporates the STN and shows that by modulating when a response is executed, the STN reduces premature responding and therefore has substantial effects on which response is ultimately selected, particularly when there are multiple competing responses.
        • Increased cortical response conflict leads to dynamic adjustments in response thresholds via cortico-subthalamic-pallidal pathways.
        • the model accounts for the beneficial effects of STN lesions on these oscillations, but suggests that this benefit may come at the expense of impaired decision making.
        • Not totally convinced -- impulsivity is due to larger network effects. Delay in conflict situations is an emergent property, not localized to STN.
      • Frank 2007 {1077}.
  • Beta band: cite Boraud et al 2005.
  • Huh parameters drawn from Misha's work, among others + Kita 2004, 2005.
    • Striatum has a low spike rate but high modulation? Schultz and Romo 1988.
  • In their model there are a wide range of parameters (bidirectional weights) which lead to oscillation
  • In PD the siatum is hyperactive in the indirect path (Obeso et al 2000); their model duplicates this.

____References____

[0] Holgado AJ, Terry JR, Bogacz R, Conditions for the generation of beta oscillations in the subthalamic nucleus-globus pallidus network.J Neurosci 30:37, 12340-52 (2010 Sep 15)

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ref: Prescott-2009.02 tags: PD levodopa synaptic plasticity SNr STN DBS date: 02-22-2012 18:28 gmt revision:2 [1] [0] [head]

PMID-19050033[0] Levodopa enhances synaptic plasticity in the substantia nigra pars reticulata of Parkinson's disease patients

  • In the SNpc -> SNr.
  • High frequency stimulation (HFS--four trains of 2 s at 100 Hz) in the SNr failed to induce a lasting change in test fEPs (1 Hz) amplitudes in patients OFF medication (decayed to baseline by 160 s). Following oral L-dopa administration, HFS induced a potentiation of the fEP amplitudes (+29.3% of baseline at 160 s following a plateau).
  • Aberrant synaptic plasticity may play a role in the pathophysiology of Parkinson's disease.

____References____

[0] Prescott IA, Dostrovsky JO, Moro E, Hodaie M, Lozano AM, Hutchison WD, Levodopa enhances synaptic plasticity in the substantia nigra pars reticulata of Parkinson's disease patients.Brain 132:Pt 2, 309-18 (2009 Feb)

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ref: Lempka-2010.12 tags: DBS current control PD date: 02-22-2012 18:25 gmt revision:2 [1] [0] [head]

PMID-20493764[0] Current-controlled deep brain stimulation reduces in vivo voltage fluctuations observed during voltage-controlled stimulation.

  • Obervation: DBS electrodes show impedance whcih varies with time and stimulation.
  • Current control may reduce the need for physicians to carefully adjust the stimulation parameters in the clinic.
  • Why did this take so long? It is a relatively obvious improvement. Perhaps efficiency -- voltage control allows longer battery life?

____References____

[0] Lempka SF, Johnson MD, Miocinovic S, Vitek JL, McIntyre CC, Current-controlled deep brain stimulation reduces in vivo voltage fluctuations observed during voltage-controlled stimulation.Clin Neurophysiol 121:12, 2128-33 (2010 Dec)

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ref: RodriguezOroz-2001.09 tags: STN SNr parkinsons disease single unit recording spain 2001 tremor oscillations DBS somatotopy organization date: 02-22-2012 18:24 gmt revision:12 [11] [10] [9] [8] [7] [6] [head]

PMID-11522580[0] The subthalamic nucleus in Parkinson's disease: somatotopic organization and physiological characteristics

  • Looks like they discovered exactly what we have discovered ... only in 2001. This is both good and bad.
    • From the abstract: "Neurones responding to movement were of the irregular or tonic type, and were found in the dorsolateral region of the STN. Neurones with oscillatory and low frequency activity did not respond to movement and were in the ventral one-third of the nucleus. Thirty-eight tremor-related neurones were recorded."
  • Again, from the abstract: "The findings of this study indicate that the somatotopic arrangement and electrophysiological features of the STN in Parkinson's disease patients are similar to those found in monkeys."
  • It may be that we want to test differential modulation / oscillation: look for differences between rest and activity, if there is sufficient support for both these in the files we have.
  • These people were much, much more careful about localization of their single-electrode tracks. E.g. they calculated electrode location relative the DBS electrode stereotatically, and referenced this to the postoperative MRI location of the treatment electrode.
  • Many more (32% of 350 neurons) responded to active or passive movement.
  • Of this same set, 15% (31 neurons) had a firing rate with rhythmical activity; 38 neurons had rhythmic activity associated with oscillatory EMG, but most of these were responsive to passive stimulation.
  • Autocorrelation of the neuronal bursting and tremor peaked at mean 7Hz, while autocorr. of EMG peaked at mean 5Hz.
  • This whole paragraph is highly interesting: ''The neuronal response associated with active movements was studied by simultaneous recording of neuronal EMG activity of the limbs. Five tremor-related neurons, recorded while a voluntary movement was performed, were available for analysis. Voluntary activation of a particular limb segment arrested the tremor. This was associated with a change in the discharges of the recorded neuron, which fired at a slower rate and in synchrony with the voluntary movement. On occasions, freezing of the voluntary movement ensued and tremor reappeared, changing the neuronal activity back to the typical 4-5Hz tremor-related activity. The cross-correlation analysis of two such neurons showed a peak frequency of 4.63 and 4.88 Hz for tremor-related activity, and 1.5 to 1.38 Hz during voluntary movement. Whether neuronal discharges in the STN preceded or followed EMG activity of the limbs could not be precisely established under the present conditions.
  • Somatotopic representation in the STN is expected from normal and MTPT-treated monkeys. Indeed, somatotopy is enhanced int he GPm of MTPT-treated monkeys.
    • This somatotopy is likely to result from organized afferent from the primary motor cortex (M1) to dorsolateral STN; this is the target of DBS treatment. Ventral and medial STN seems to project to associative and limbic cortical regions.
    • It seems they think the STN is generally not diseased, it is just a useful target for stimulating without evoked movement as in M1. This is consistent with optogenetic studies by Deisseroth [1].
    • Supporting this: "DBS of STN in Parkinson's disease improves executive motor functions, but aggravates conditional associative learning.
  • Interesting: In Parkinson's disease patients with tremor, Levy and colleagues found synchronization and a high firing rate (>10Hz) while recording pairs of neurons >600um apart.
  • Recordings of cortical activity through EEG and STN LFP showed significant coherence in the beta and gamma frequency bands during movement - consistent with corticosubthalamic motor projection. ... and suggest that the STN neurons involved in parkinsonian tremor are the same as the ones ativated during the performance of a voluntary movement. (! -- I agree with this.)
  • More: The reciprocal inhibitory-excitatory connections tightly linking the GPe and the STN may generate self-perpetuating oscillations.

Old notes:

  • this paper concentrates on STN electrophysiology in PD.
    • has a rather excellent list of references.
  • found a somatotopic organization in the STN, with most motor-related units more irregular and in the dorsolateral STN.
  • found a substantial fraction of tremor-synchronized neurons.
  • conclude that the somatotopic organization is about the same as in monkeys (?) (!)
  • M1 projects to STN, as verified through anterograde tracing studies. [1] These neurons increase their firing rate in response to passive movements.
  • there appears to be a relatively-complete representation of the body in the dorsolateral STN.

____References____

[0] Rodriguez-Oroz MC, Rodriguez M, Guridi J, Mewes K, Chockkman V, Vitek J, DeLong MR, Obeso JA, The subthalamic nucleus in Parkinson's disease: somatotopic organization and physiological characteristics.Brain 124:Pt 9, 1777-90 (2001 Sep)
[1] Gradinaru V, Mogri M, Thompson KR, Henderson JM, Deisseroth K, Optical deconstruction of parkinsonian neural circuitry.Science 324:5925, 354-9 (2009 Apr 17)

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ref: Salin-2002.06 tags: STN HFS DBS stimulation dopamine date: 02-22-2012 18:23 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

PMID-12077209[0][] High-frequency stimulation of the subthalamic nucleus selectively reverses dopamine denervation-induced cellular defects in the output structures of the basal ganglia in the rat.

  • they wanted to measure the cellular/molecular effects of STN DBS - reasonable.
    • in-situ hybridization histochemistry and immunocytochemnistry.
  • HFS of the STN decreases the metabolic activity of STN neurons (cytochrome oxidase (CoI) levels decreased!),
    • However it did not affect the overexpression of enkephalin {1135} mRNA or the decrease in substance P in the ipsilateral striatum.
    • Decreased/corrects glutamate decarboxylase 67 (GAD67) in the substantia nigra following STN lesion, worsened in the entopeduncular (GPe-ish: see wiki) nucleus, no change in GPi.
    • HFS, however, increases c-fos activity, which seems to be involved in immediate early gene induction and stress response (as well as 8,000 other papers about this protein)
  • this stimulation may not simply cause interruption of STN outflow.
  • STN on the order of 300ua through a 200um teflon-coated stainless bipolar (twisted pair) electrode (important to consider)
  • unilateral HFS in STN in hemiparkinsonian rats can induce dyskinesias
    • buuut a higher intensity of stimulation was required to elicit dyskinesia in animals with the dopamine lesion as compared to the intact rats. Parkinsonian animals are more resistant to HFS of the STN.
    • Therefore they matched the stimulus intensity to the behavior correlates, not the absolute values of the currents.
  • STN HFS in animals with dopamine lesions on the same brain side may prevent the previously reported dopamine hyperactivity in the contralateral hemisphere.
  • note bene, the entopeduncular nucleus is probably not a good taget for surgical treatment PMID-14602091[1][] High frequency stimulation of the entopeduncular nucleus has no effect on striatal dopaminergic transmission.

____References____

[0] Salin P, Manrique C, Forni C, Kerkerian-Le Goff L, High-frequency stimulation of the subthalamic nucleus selectively reverses dopamine denervation-induced cellular defects in the output structures of the basal ganglia in the rat.J Neurosci 22:12, 5137-48 (2002 Jun 15)
[1] Meissner W, Harnack D, Hoessle N, Bezard E, Winter C, Morgenstern R, Kupsch A, High frequency stimulation of the entopeduncular nucleus has no effect on striatal dopaminergic transmission.Neurochem Int 44:4, 281-6 (2004 Mar)

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ref: -0 tags: enkephalin DBS dopamine regulation date: 02-22-2012 18:22 gmt revision:0 [head]

PMID-9835393 Role of dynorphin and enkephalin in the regulation of striatal output pathways