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[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] 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] Schmidt EM, Single neuron recording from motor cortex as a possible source of signals for control of external devices.Ann Biomed Eng 8:4-6, 339-49 (1980)[1] 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)[2] Salcman M, Bak MJ, A new chronic recording intracortical microelectrode.Med Biol Eng 14:1, 42-50 (1976 Jan)

[0] Aflalo TN, Graziano MS, Relationship between unconstrained arm movements and single-neuron firing in the macaque motor cortex.J Neurosci 27:11, 2760-80 (2007 Mar 14)

[0] Shuler MG, Bear MF, Reward timing in the primary visual cortex.Science 311:5767, 1606-9 (2006 Mar 17)

[0] Atallah HE, Lopez-Paniagua D, Rudy JW, O'Reilly RC, Separate neural substrates for skill learning and performance in the ventral and dorsal striatum.Nat Neurosci 10:1, 126-31 (2007 Jan)

[0] Mehta MR, Cortico-hippocampal interaction during up-down states and memory consolidation.Nat Neurosci 10:1, 13-5 (2007 Jan)[1] Ji D, Wilson MA, Coordinated memory replay in the visual cortex and hippocampus during sleep.Nat Neurosci 10:1, 100-7 (2007 Jan)

[0] Ji D, Wilson MA, Coordinated memory replay in the visual cortex and hippocampus during sleep.Nat Neurosci 10:1, 100-7 (2007 Jan)

[0] Recanzone GH, Schreiner CE, Merzenich MM, Plasticity in the frequency representation of primary auditory cortex following discrimination training in adult owl monkeys.J Neurosci 13:1, 87-103 (1993 Jan)

[0] Isoda M, Hikosaka O, Switching from automatic to controlled action by monkey medial frontal cortex.Nat Neurosci 10:2, 240-8 (2007 Feb)

[0] Sabelli HC, Mosnaim AD, Vazquez AJ, Giardina WJ, Borison RL, Pedemonte WA, Biochemical plasticity of synaptic transmission: a critical review of Dale's Principle.Biol Psychiatry 11:4, 481-524 (1976 Aug)[1] Sulzer D, Rayport S, Dale's principle and glutamate corelease from ventral midbrain dopamine neurons.Amino Acids 19:1, 45-52 (2000)[2] Burnstock G, Do some nerve cells release more than one transmitter?Neuroscience 1:4, 239-48 (1976 Aug)

[0] Ashe J, Georgopoulos AP, Movement parameters and neural activity in motor cortex and area 5.Cereb Cortex 4:6, 590-600 (1994 Nov-Dec)

[0] Sergio LE, Kalaska JF, Systematic changes in motor cortex cell activity with arm posture during directional isometric force generation.J Neurophysiol 89:1, 212-28 (2003 Jan)

[0] Taira M, Boline J, Smyrnis N, Georgopoulos AP, Ashe J, On the relations between single cell activity in the motor cortex and the direction and magnitude of three-dimensional static isometric force.Exp Brain Res 109:3, 367-76 (1996 Jun)

[0] Wahnoun R, Helms Tillery S, He J, Neuron selection and visual training for population vector based cortical control.Conf Proc IEEE Eng Med Biol Soc 6no Issue 4607-10 (2004)[1] Wahnoun R, He J, Helms Tillery SI, Selection and parameterization of cortical neurons for neuroprosthetic control.J Neural Eng 3:2, 162-71 (2006 Jun)[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)[6] Humphrey DR, Schmidt EM, Thompson WD, Predicting measures of motor performance from multiple cortical spike trains.Science 170:959, 758-62 (1970 Nov 13)

[0] Fu QG, Suarez JI, Ebner TJ, Neuronal specification of direction and distance during reaching movements in the superior precentral premotor area and primary motor cortex of monkeys.J Neurophysiol 70:5, 2097-116 (1993 Nov)

[0] Amirikian B, Georgopoulos AP, Directional tuning profiles of motor cortical cells.Neurosci Res 36:1, 73-9 (2000 Jan)

[0] 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)

[0] Teich MC, Heneghan C, Lowen SB, Ozaki T, Kaplan E, Fractal character of the neural spike train in the visual system of the cat.J Opt Soc Am A Opt Image Sci Vis 14:3, 529-46 (1997 Mar)

[0] Vyssotski AL, Serkov AN, Itskov PM, Dell'Omo G, Latanov AV, Wolfer DP, Lipp HP, Miniature neurologgers for flying pigeons: multichannel EEG and action and field potentials in combination with GPS recording.J Neurophysiol 95:2, 1263-73 (2006 Feb)[1] Otto KJ, Johnson MD, Kipke DR, Voltage pulses change neural interface properties and improve unit recordings with chronically implanted microelectrodes.IEEE Trans Biomed Eng 53:2, 333-40 (2006 Feb)

{1387}
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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.

{1384}
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ref: -0 tags: NET probes SU-8 microfabrication sewing machine carbon fiber electrode insertion mice histology 2p date: 03-01-2017 23:20 gmt revision:0 [head]

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.

{1381}
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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)

{1377}
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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.

{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.

{1362}
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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.

{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}

{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)

{1347}
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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 !!

{1346}
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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!

{1328}
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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?

{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.

{875}
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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)

{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.

{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.

{1275}
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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.

{1260}
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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!

{1248}
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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.

{1247}
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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.

{1193}
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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)

{597}
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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____

{823}
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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)

{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)

{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)

{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)

{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)

{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)

{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

{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)

{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)

{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}

{158}
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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)

{164}
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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: 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: Hamani-2004.01 tags: STN subthalamic nucleus movement disorders PD parkinsons basal_ganglia globus_pallidus anatomy DBS date: 02-22-2012 15:03 gmt revision:8 [7] [6] [5] [4] [3] [2] [head]

PMID-14607789[0] The subthalamic nucleus in the context of movement disorders

  • this is a good anatomy article, very descriptive -- almost too much information to grapple with.
  • STN = important structure for the modulation of activity of basal ganglia structures
  • STN is anterior-adjacent to the red nucleus
  • The average number of neurons in each STN nucleus varies from species to species and has been estimated to be ~25 000 in rats, 35 000 in marmosets, 155 000 in macaques, 230 000 in baboons and 560 000 in humans
  • The volume of the STN is ~0.8 mm3 in rats, 2.7 mm3 in marmosets, 34 mm3 in macaques, 50 mm3 in baboons and 240 mm3 in humans.
    • Number of neurons does not scale with volume, uncertain why not.
  • STN is divided into three functional units: motor, associative, and limbic cortical regions innervate, respectively motor, associative, and limbic regions of the striatum, pallidium SNr.
    • they give a complete list of these 3 in 'intrinsic organization of the STN'
    • STN is divided into 2 rostral thirds and one cauldal third.
      • medial rostral = limbic and associative
      • lateral rostral = associative
      • dorsal = motor circuits. (the largest part, see figure 2)
        • hence, the anterodorsal is thought to be the most effective target for DBS.
  • STN is populated primarily by projection neurons
  • the dendritic field of a single STN neurons can cover up to one-half of the nucleus of rodents
  • efferent projections (per neuron, branched axons)
    • GPe, GPi, SNr 21.3%
    • GPe and SNr 2.7%
      • in both segments of the pallidum, projections are uniformly arborized & affect an extensive number of cells.
    • GPe and GPi 48%
    • GPe only 10.7%
    • 17.3% remaining toward the striatum
  • most of the cortical afferents to the STN arise from the primary motor cortex, supplementary motor area, pre-SMA, and PMd and PMv; these target the dorsal aspects of the STN.
    • afferents consist of collaterals from the pyramidal tract (layer 5) & cortical fibers that also innervate the striatum (latter more prevalent). afferents are glutamergic.
  • ventromedial STN recieves afferents from the FEF (area 8) and suppl.FEF (9)
  • GPe projects extensively to STN with GABA. see figure 3 [1]
    • almost every cell in the STN resonds to pallidal GABAergic stimulation.
    • 13.2% of GPe neurons project to GPi, STN, and SNr
    • 18.4% to GPI and STN,
    • 52.6% to only the STN and SNr
    • 15.8% remaining to the striatum.
  • DA afferents from the SNc
  • ACh from the tegmentum
  • Glutamergic afferents from the centromedian thalamus (CM)
  • Serotonin from the raphe nucleus
  • fibers from the tegmentum, SNc, motor cortex, VM.pf of the thalamus, and dorsal raphe synapse on distal dendrites
    • pallidal inhibitory fibers innervate mostly proximal dendrites and soma.
firing properties:
  • about half of STN neurons fire irregularly, 15-25% regularly, 15-50% burst.
    • bursting is related to a hyperpolarization of the cell.
  • movement-related neurons are in the dorsal portion of STN and are activated by either/both active/passive movements of single contralateral joints
  • there is a somatotopic organizaton, but it is loose.
  • many units are responsive to eye fixation, saccadic movements, or visual stim. these are in the ventral portion.
    • activation of the STN drives SNr activity, which inhibits the superior colliculus, allowing maintainance of eye position on an object of interest.
  • ahh fuck: if high currents are delivered to STN or high concentrations of GABAergic antagonists are applied abnormal movements such as dyskinesias can be elicited
    • low concentrationns of GABA antagonists induces postural asymmetry and abnormal movements, but no excessive locomotion.
  • dyskinesias result from high-frequency or high-current stimulation to the STN! low frequency stimulation induces no behavioral effects. [2]
  • small (<4% !!) lesions cause focal dystonias
  • in parkinsonian patients, activity in the STN is characterized by increased synchrony and loss of specificity in receptive fields + mildly increased mean firing rate.
    • 55% of STN units in PD patients respond to passive movements, and 24% to ipsilateral movements (really?) - indicative of the increase in receptive field size caused by the disease.

____References____

[0] Hamani C, Saint-Cyr JA, Fraser J, Kaplitt M, Lozano AM, The subthalamic nucleus in the context of movement disorders.Brain 127:Pt 1, 4-20 (2004 Jan)
[1] Sato F, Lavallée P, Lévesque M, Parent A, Single-axon tracing study of neurons of the external segment of the globus pallidus in primate.J Comp Neurol 417:1, 17-31 (2000 Jan 31)
[2] Beurrier C, Bezard E, Bioulac B, Gross C, Subthalamic stimulation elicits hemiballismus in normal monkey.Neuroreport 8:7, 1625-9 (1997 May 6)

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ref: Fellows-2006.04 tags: parkinsons subthalamic nucleus thalamus DBS STN force velocity overshoot grasp date: 02-22-2012 14:51 gmt revision:9 [8] [7] [6] [5] [4] [3] [head]

PMID-16549385[0] The effect of subthalamic nucleus deep brain stimulation on precision grip abnormalities in Parkinson's disease

  • Deep Brain stimulation improves mobility/dexterity and dyskinesia of patients in general, via an increase in rate and decrease in reaction time, but it does not let the patient match force output to the object being manipulated (that is, the force is too large).
  • The excessive levels of grip force present in the stimulation 'off' state, and present from the early stages of the disease, however, were even more marked with STN stimulation on.
    • STN DBS may worsen the ability to match force characteristics to task requirements. (position control is improved?).
    • quite fascinating.

See also PMID-19266149[1] Distal and proximal prehension is differentially affected by Parkinson‘s disease The effect of conscious and subconscious load cues

  • asked PD and control patients to lift heavy and light objects.
  • While controls were able to normalize lift velocity with the help of both conscious and subconscious load cues, the PD patients could use neither form of cue, and retained a pathological overshoot in lift velocity.
  • Hence force control is remarkably affected in PD, which is consistent with the piper rhythm being absent / usually present for isometric contraction.

____References____

[0] Fellows SJ, Kronenbürger M, Allert N, Coenen VA, Fromm C, Noth J, Weiss PH, The effect of subthalamic nucleus deep brain stimulation on precision grip abnormalities in Parkinson's disease.Parkinsonism Relat Disord 12:3, 149-54 (2006 Apr)
[1] Weiss PH, Dafotakis M, Metten L, Noth J, Distal and proximal prehension is differentially affected by Parkinson's disease. The effect of conscious and subconscious load cues.J Neurol 256:3, 450-6 (2009 Mar)

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ref: Snow-2006.02 tags: electrode insertion sharp recording tissue surrogate date: 02-10-2012 18:56 gmt revision:4 [3] [2] [1] [0] [head]

IEEE-1580838 (pdf) Microfabricated cylindrical multielectrodes for neural stimulation.

  • Used optical fiber as the substrate.
  • sharpened using a Dicing saw.
  • polymide insulatino removed by placing fiber tip next to a white-hot platinum filament.
  • cylindrical lithography system using a He-Cd laser.
  • tissue surrogate: two layers of 20um Saran Wrap over tofu. (!!!) -- see also {212}

____References____

Snow, S. and Jacobsen, S.C. and Wells, D.L. and Horch, K.W. Microfabricated cylindrical multielectrodes for neural stimulation Biomedical Engineering, IEEE Transactions on 53 2 320 -326 (2006)

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ref: Nishioka-2008.12 tags: STN hemiballismus lesion stroke MRI neurosurgery date: 01-26-2012 17:31 gmt revision:3 [2] [1] [0] [head]

PMID-18842415[0] Transient hemiballism caused by a small lesion of the subthalamic nucleus.

  • Hemiballism is most commonly caused by ischemic stroke and most cases have a favorable prognosis.
  • Lesions directly involving the subthalamic nucleus (STN) are the cause of a minority of cases but are usually associated with poor prognosis.
  • We report two patients with a small STN lesion who presented with transient hemiballism.
  • This may be a useful ref in the future.
  • This reports the same result: PMID-17702635

____References____

[0] Nishioka H, Taguchi T, Nanri K, Ikeda Y, Transient hemiballism caused by a small lesion of the subthalamic nucleus.J Clin Neurosci 15:12, 1416-8 (2008 Dec)

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ref: Lee-2005.07 tags: STN subthalamic nucleus hemiballismus DBS date: 01-26-2012 17:24 gmt revision:3 [2] [1] [0] [head]

PMID-16032642[0] Common causes of hemiballism.

  • stroke of the STN results in hemiballismus - wild movements of the limbs. recall the input to the STN is inhibitory from GPe, and the output is exitatory to the GPi. chemical treatment is via dopamine blockade (1976!)
  • hemiballism is rare, but usually associated with lesion to the contralateral STN.
    • however, half the cases of hemiballismus are associated with damage to the afferent or efferent pathways to the STN.
    • diabetes type 2 also commonly causes hemiballismus (hyperglycemia in asian women!)
  • hemiballismus is absent in sleep - the thalamocortical relay must be turned off.
  • hemiballismus is generally associated with high metabolic activity in the basal ganglia.
  • does this mean that stimulation to the STN in healthy monkeys will disinhibit large, possibly conflicting movements?
  • my thought: the subthalamic nucleus must be involved in the selection and regulation of appropriate movements.

____References____

[0] Lee HS, Kim SW, Yoo IS, Chung SP, Common causes of hemiballism.Am J Emerg Med 23:4, 576-8 (2005 Jul)

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ref: Sato-2000.01 tags: globus_pallidus anatomy STN GPi GPe SNr substantia nigra tracing DBS date: 01-26-2012 17:20 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

PMID-10660885[0] Single-axon tracing study of neurons of the external segment of the globus pallidus in primate.

  • wow, check out the computerized tracing! the neurons tend to project to multiple areas, usually. I didn't realize this. I imagine that it is relatively common in the brain.
  • complicated, tree-like axon collateral projection from GPe to GPi.
    • They look like the from through some random-walk process; paths are not at all efficient.
    • I assume these axons are mylenated? unmylenated?
  • dendritic fields in the STN seem very dense.
  • study done in cyno. rhesus

____References____

[0] Sato F, Lavallée P, Lévesque M, Parent A, Single-axon tracing study of neurons of the external segment of the globus pallidus in primate.J Comp Neurol 417:1, 17-31 (2000 Jan 31)

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ref: Bergman-1994.08 tags: subthalamic nucleus STN basal ganglia globus pallidus electrophysiology 1994 MPTP DBS date: 01-26-2012 17:19 gmt revision:3 [2] [1] [0] [head]

PMID-7983515[0] The primate subthalamic nucleus. II. Neuronal activity in the MPTP model of parkinsonism

  • idea: record from STN and GPi before and after MPTP treatment in green monkeys.
  • recorded 4-8hz periodic activity (via autocorrelograms) in significantly more neurons from the MPTP treated animals in both the STN and GPi.
  • mean firing rate was increased in STN,
  • tremor-correlated cells found in both.
  • burst activity higher in both, too.
  • modulations in firing rate due to the application of flexion and extension torque pulses were higher in MPTP animals (duration and amplitude), in both areas.
  • spikes were longer in MPTP
  • no tyrosene hydroxylase activity in the PD mks.
  • PD tremor only frequently occurs in green mks following MPTP

____References____

[0] Bergman H, Wichmann T, Karmon B, DeLong MR, The primate subthalamic nucleus. II. Neuronal activity in the MPTP model of parkinsonism.J Neurophysiol 72:2, 507-20 (1994 Aug)

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ref: Monakow-1978.11 tags: motor_cortex STN subthalamic nucleus anatomy DBS date: 01-26-2012 17:17 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-83239[0] Projections of the precentral motor cortex and other cortical areas of the frontal lobe to the subthalamic nucleus in the monkey.

  • this paper is old and important!
  • The ipsilateral subthalamic nucleus receives a moderately strong and somatotopic organized projection from Woolsey's precentral motor cortex (PMd, M1 i guess)
    • No projections from the postcentral gyrus! (S1) (Is this still thought to be true?)
  • The remaining nucleus is occupied by less intensive projections from premotor and prefrontal areas
  • STN is a convergence site for pallidal and cortical motor/frontal projections.
  • autoradiography slices are damn hard for me to read.

____References____

[0] Monakow KH, Akert K, Künzle H, Projections of the precentral motor cortex and other cortical areas of the frontal lobe to the subthalamic nucleus in the monkey.Exp Brain Res 33:3-4, 395-403 (1978 Nov 15)

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ref: Lehericy-2005.08 tags: fMRI motor_learning basal_ganglia STN subthalamic date: 01-25-2012 00:20 gmt revision:2 [1] [0] [head]

PMID-16107540[0] Distinct basal ganglia territories are engaged in early and advanced motor sequence learning

  • generally a broad, well-referenced study.
  • they used a really high-field magnet (3T) during tapping-learning task over the course of a month.
  • STN was activated early in motor learning, but not afterward, specifically the sequence learning
  • during the course of learning (an as the task became progressively more automatic) associative striatal activation shifted to motor activity.
    • STN could act by inhibiting competing motor outputs, thus building a temporally ordered sequence of movements.
  • SN was active throughout the course of the experiment.
  • during the 'fast learning' stage, there was transient activation of the ACC
  • also during the beginning portion of motor learning lobules V and VI of the cerebellum were activated.
  • rostral premotor and prefrontal cortical areas are connected to the associative territory of the striatum, which projects back to the frontal cortex the VA/VL nuclei of the thalamus.

____References____

[0] Lehéricy S, Benali H, Van de Moortele PF, Pélégrini-Issac M, Waechter T, Ugurbil K, Doyon J, Distinct basal ganglia territories are engaged in early and advanced motor sequence learning.Proc Natl Acad Sci U S A 102:35, 12566-71 (2005 Aug 30)

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ref: Breit-2006.1 tags: parkinsons basal_ganglia palladium substantia_nigra motor_control striate date: 01-24-2012 22:10 gmt revision:1 [0] [head]

I wish i could remember where i got these notes from, so as to verify the somewhat controversial statements. I found them written on the back of a piece of scrap paper.

  • neurophysiological recordings in animals show that over half of basal ganglia neurons fire in response to motor activity but none are triggered by passive limb movement.
  • in parkinson's disease (PD), the substantia nigra actually becomes pale to the eye.
  • stimulation of the striatum does not result in low-threshold movements like stimulation of the cortex does.
  • palladium does not seem linked to motor planning. (just execution?)
  • stimulation of the caudate causes movement, i.e. head turning, while stimulation of the ventromedial caudate produces arrest and crouching movements. (Delgado etc)
  • large bilateral striatal leasions cause inattention.
  • striatal units appear to signal movement, not generate/compute it (really?)
  • in parkinson's disease, motor learning appears normal - it is the initial slowness that is abnormal :: PD relates to the quality of movement, not the quality of the motor commands. Thus, perhaps PD is a disease of gating/attention?
  • in PD, all reflexes except the Hoffman-reflex appear normal.
    • The primary difference between the H-reflex and the spinal stretch reflex is that the H-reflex bypasses the muscle spindle and, therefore, is a valuable tool in assessing modulation of monosynaptic reflex activity in the spinal cord. The H-reflex is an estimate of alpha motoneuron ( alpha MN) excitability when presynaptic inhibition and intrinsic excitability of the alpha MNs remain constant.
  • A lesion of the PPN (pedunculo pontine nucleus) was shown to restore decreased activity levels in the SNr and STN of a rat model of parkinson's (lesion of the SNc) PMID-17042796

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ref: Krack-2001.09 tags: STN subthalamic nucleus stimulation PD parkinsons DBS date: 01-24-2012 05:48 gmt revision:1 [0] [head]

PMID-11746616[0] Mirthful laughter induced by subthalamic nucleus stimulation.

  • high stimulation parameters induces mirthful laughter
  • prescribed parameters induced hypomanic behavior with marked improvement in akinesia.
  • STN must be involved in psychomotor as well as motor regulation.

____References____

[0] Krack P, Kumar R, Ardouin C, Dowsey PL, McVicker JM, Benabid AL, Pollak P, Mirthful laughter induced by subthalamic nucleus stimulation.Mov Disord 16:5, 867-75 (2001 Sep)

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ref: Hilker-2004.01 tags: STN subthalamic DBS stimulation cortex cerebellum PET PD parkinsons date: 01-24-2012 05:38 gmt revision:1 [0] [head]

PMID-14688612[0] Subthalamic Nucleus Stimulation Restores Glucose Metabolism in Associative and Limbic Cortices and in Cerebellum: Evidence from a FDG-PET Study in Advanced Parkinson's Disease

  • cortical depression of glucose metabolism
  • hypermetabolic state in the left rostral cerebellum (?!)
  • DBS generally remedies this imbalance, restoring glucose metabolism to the cortex associative/motor/frontal as well as to the thalamus distant from the stimulation site.

____References____

[0] Hilker R, Voges J, Weisenbach S, Kalbe E, Burghaus L, Ghaemi M, Lehrke R, Koulousakis A, Herholz K, Sturm V, Heiss WD, Subthalamic nucleus stimulation restores glucose metabolism in associative and limbic cortices and in cerebellum: evidence from a FDG-PET study in advanced Parkinson's disease.J Cereb Blood Flow Metab 24:1, 7-16 (2004 Jan)

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ref: Zhang-2009.02 tags: localized surface plasmon resonance nanoparticle neural recording innovative date: 01-15-2012 23:00 gmt revision:4 [3] [2] [1] [0] [head]

PMID-19199762[0] Optical Detection of Brain Cell Activity Using Plasmonic Gold Nanoparticles

  • Used 140 nm diameter, 40 nm thick gold disc nanoparticles set in a 400nm array, illuminated by 850nm diode laser light.
    • From my reading, it seems that the diameter of these nanoparticles is important, but the grid spacing is not.
  • These nanoparticles strongly scatter light, and the degree of scattering is dependent on the local index of refraction + electric field.
  • The change in scattering due to applied electric field is very small, though - ~ 3e-6 1/V in the air-capacitor setup, ~1e-3 in solution when stimluated by cultured hippocampal neurons.
  • Noteably, nanoparticles are not diffraction limited - their measurement resolution is proportional to their size. Compare with voltage-sensitive dyes, which have a similar measurement signal-to-noise ratio, are diffraction limited, may be toxic, and may photobleach.

____References____

[0] Zhang J, Atay T, Nurmikko AV, Optical detection of brain cell activity using plasmonic gold nanoparticles.Nano Lett 9:2, 519-24 (2009 Feb)

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ref: Maschietto-2009.07 tags: recording ASIC surface recording date: 01-15-2012 22:06 gmt revision:1 [0] [head]

IEEE-5230909 (pdf) A High Resolution Bi-Directional Communication through a Brain-Chip Interface

  • 1000 channels, 10um pitch if thin-film transistors.
  • innovative!
  • EOSFET - electrolyte oxide semiconductor field effect transistor.

____References____

Maschietto, M. and Mahmud, M. and Stefano, G. and Vassanelli, S. Advanced Technologies for Enhanced Quality of Life, 2009. AT-EQUAL '09. 32 -35 (2009)

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ref: Schmidt-1980.01 tags: BMI 1980 SUA M1 prosthetics Schmidt MEA date: 01-04-2012 22:59 gmt revision:14 [13] [12] [11] [10] [9] [8] [head]

PMID-6794389[0] Single neuron recording from motor cortex as a possible source of signals for control of external devices

  • also [1]
  • I guess this was the first published article claiming that motorneurons could be used to drive a prosthesis, and first clear attempt at long-term array recording (?)
  • recorded via arrays for up to 37 months!
    • only 2 of the 11 eelctrodes were recording at the time of sacrifice.
  • trained the monkey to perform an 8 target tracking task
    • with cortical neurons: 2.45 bits/second
    • with wrist flexion/extension: 4.48 bits/second
  • electrodes: {946} A new chronic recording intracortical microelectrode (1976!)
    • 25um iridium wires electropolished to a 1um tip; 1.5mm long.
    • electrodes float on the cortex; signals transmitted through 25um gold wire, which is in turn connected to a head-mounted connector.
    • iridium and gold are insulated with vapor-deposited parylene-C
    • electrode tips are exposed with a HV arc. (does this dull them? from the electromicrograph, it seems that it just makes them rougher.)
    • arrays of 12.
    • 1M impedance (average)
  • interesting: neural activity was recorded from at least 8 different neurons with this electrode during the course of the implant, indicating that it was migrating through cortical tissue.
    • the average recording time from the same electrode was 8 days; max 23 days.
  • second implant was more successful: maximium time recording from the same neuron was 108 days.
  • failure is associated with cracks in the parylene insulation (which apparently occurred on the grain boundaries of the iridium). "still only marginally reliable" (and still.. and still..)
  • they have operantly trained cortical units in another, earlier study.
  • have, effectively, 8 levels of activity, with feedback monkey has to match the proscribed firing rate.
  • > 50% rewarded trials = success for them; 26/28 of the neurons tested were eventually conditioned successfully.
  • looks like the monkey can track the target firing rate rather accurately. "the output of cortical cells can provide information output rates moderately less precise than the intact motor system. "
  • Monkey can also activated sequences of neurons: A, then AB, then B.
  • people have also tried conditioning individual EMG units; it is sometimes possible to control 2 different motor units in the same muscle independently, but in general only a single channel of information can be obtained from one muscle, and gross EMGs are fine for this.
    • Thus surface EMG is preferred.
    • you can get ~ 2.73 bits/sec with gross EMG on a human; 2.99 bits/sec (max) with a monkey.
  • they remind us, of course, that an enormous amount of work remains to be done.

____References____

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ref: Penfield-1937 tags: Penfield 1937 motor cortex stimulation ICMS human neurosurgery electrodes date: 01-03-2012 22:08 gmt revision:3 [2] [1] [0] [head]

No PMID / bibtex penfield-1937. Somatic motor and sensory representation in the cerebral cortex of man as studied by electrical stimulation

  • Fritsch and Hitzig (1870) [0] cited as the first paper in electrical excitation of the CNS.
  • Good review of the scientific experiments thereafter, including stimulation to S1 by Ferrier, work with apes etc.
  • Central sulcus called the 'Rolandic fissure'.
  • Interesting! quote:

The account of Bartholow (1874) is interesting to say the least and may be cited. His patient was a 30-year old-domestic. As an infant this unfortunate had chanced to fall into the fire, burning her scalp so badly that " hair was never reproduced." A piece of whale bone in the wig she was forced to wear irritated the scarred scalp and, by her statement, three months before she was admitted, an ulcer appeared. When she presented herself for relief, this had eroded the skull over a space 2 in. in diameter " where the pulsations of the brain are plainly seen." Although " rather feeble-minded " Bartholow observed that Mary returned replies to all questions and no sensory or motor loss could be made out in spite of the fact that brain substance apparently had been injured in the process of evacuation of pus from the infected area. The doctor believed, therefore, that fine insulated needles could be introduced without further damage.

While the electrodes were in the right side Bartholow decided to try the effect of more current. ' Her countenance exhibited great distress and she began to cry. Very soon the left hand was extended as if in the act of taking hold of some object in front of her; the arm presently was agitated with clonic spasms ; her eyes became fixed with pupils widely dilated ; the lips were blue and she frothed at the mouth ; her breathing became stertorous, she lost conscious-ness and was violently convulsed on the left side. This convulsion lasted for five minutes and was succeeded by coma. She returned to consciousness in twenty minutes from the beginning of the attack and complained of some weakness and vertigo." Three days after this stimulation, following a series of right-sided seizures, the patient died.

  • Relatively modern neurosurgical procedures.
  • They observe changes to blood circulation prior epileptic procedures. wow!
  • Very careful hand-drawn maps of what they have observed. Important, as you'll probably never get this trough an IRB. It pays to be meticulous.

____References____

[0] Fritsch G, Hitzig E, Electric excitability of the cerebrum (Uber die elektrische Erregbarkeit des Grosshirns).Epilepsy Behav 15:2, 123-30 (2009 Jun)

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ref: Delgado-1964 tags: Delgado wireless stimulation record stimoceiver rhesus monkey date: 01-03-2012 07:07 gmt revision:5 [4] [3] [2] [1] [0] [head]

bibtex: delgado-1964 Personality, education, and electrical stimulation of the brain

  • images/977_1.pdf
  • "Is it conceivable that behavior or the psyche can be related to electronics? Before answering these questions, we should ask one more: what is the main difference between primitive tribesmen still living in the jungle and the civilized human beings so well represented by this audience?" Education.
  • Kinda a ramble saying how education and understanding the brain is essential to our future.
  • Against atomic deterrence, unsurprisingly.
    • We are in the precarious race between the acquisition of many megatons of destructive power and the development of intelligent human beings who will make wise use of the forces at our disposal"
  • Radio receiver on a belt.
  • Elicited very complex movements from stimulating the thalamus, including walking from one side of the cage to the other, including avoiding the boss monkey!
    • He calls this 'electrical stimulation of the will'.
  • stimulate nucleus postero-ventralis induces targeted, well-directed attacks against other males of the group.
  • Stimulation of the caudate-septal lobes, just behind the frontal lobes, causes the boss monkey to become tame / tolerant / less aggressive.
  • When this function was enabled by pressing a button in the monkeys cage, the monkey most harrassed learned to press the button to halt the boss's aggressive behavior.
  • Regarding patients: "some of these patients have undergone testing for weeks or months, and lead a nearly normal life wthile 10, 20 or even more fine wires were present, in different cerebral areas and ready for stimulation from outside the scalp."
    • For example, in one patient, who spike a mean of 8.5 words per minute, by means of stimulation to the second temporal column increased his conversation to 44 words per minute." Menwhile, the number of friendly remarks increased by a factor of 9.
  • "Knowledge of the human mind may be decisive for our pursuit of happiness and for the very existence of mankind"

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ref: Aflalo-2007.03 tags: Graziano motor cortex M1 SUA macaque monkey electrophysiology tuning date: 01-03-2012 03:37 gmt revision:1 [0] [head]

PMID-17360898[] Relationship between Unconstrained Arm Movements and Single-Neuron Firing in the Macaque Motor Cortex

  • the best explanation of neuronal firing was the final mulijoint configuration of the arm - it accounted for 36% of the SUA variance.
  • the search for the 'correct' motor parameter (that neurons are tuned to) is an ill-posed experimental question because motor parameters are very intercorrelated.
  • they knock experiments in which the animals are overtrained & the movements limited - and they are right!
  • single electrode recording with cronically implanted steel chamber - e.g. it took a damn long time!
    • imaged the central sulcus through the dura.
    • verified location with single unit responses to palpation of the contralateral hand/arm (in S1) & microstimulation-evoked movements in M1.
  • used optotrak to measure the position of the monkey.
  • occasionally, the monkey attemptted to scratch the experimenter with fast semi-ballistic arm movement. heh. :)
  • movements were seprarated based on speed analysis - that is, all the data were analyzed as discrete segments.
  • neurons were inactive during periods of hand stasis between movements.
  • tested the diversity of their training set in a clever way: they simulated neurons tuned to various parameters of the motion, and tested to see if their analysis could recover the tuning. it could.
    • however, they still used unvalidated regression analysis to test their hypothesis. regression analysis estimates how much variance is estimated by the cosine-tuning model - it returns an R^2.
  • either averaged the neuronal tuning over an entire movement or smoothed the firing rate using a 10hz upper cutoff.
  • Moran & Schwartz' old result seems to be as much a consequence of averaging across trials as it is a consequence of actual tuning...
    • whithout the averaging, only 3% of the variance could be attributed to speed tuning.
  • i think that they have a good point in all of this: when you eliminate sources of variance (e.g. starting position) from the behavior, either by mechanical restraint or simple omission of segments or even better averaging over trials, you will get a higher R^2. but it may be false, a compression of the space along an axis where they are not well correlated!
  • a model in which the final position matters little, but the velocity used to get there does, has been found to account for little of the neuronal variance.
    • instead, neurons are tuned to any of a number of movements that terminate near a preferred direction.
  • observational studies of of the normal psontaneous behavior of monkeys indicate that a high proportion of time is spent using the arm as a postural device.
    • therefore, they expect that neurons are tuned to endpoint posture.
    • modeled the neuronal firing as a gaussian surface in the 8-dimensional space of the arm posture.
  • in comparison to other studies, the offset between neural activity and behavior was not significantly different, over the entire population of recorded neurons, from zero. This may be due to the nature of the task, which was spontaneous and ongoing, not cue and reaction based, as in many other studies.
    • quote: This result suggests that the neuronal tuning to posture reflects reatively more and anticipation of the future state of the limb rather than a feedback signal about a recent state of the limb.

____References____

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ref: Donoghue-1990.01 tags: Donoghue Suner Sanes rat motor cortex reorganization M1 tuning surprising date: 01-03-2012 03:30 gmt revision:4 [3] [2] [1] [0] [head]

PMID-2340869[0] Dynamic organization of primary motor cortex output to target muscles in adult rats. II. Rapid reorganization following motor nerve lesions.

  1. Map out the motor cortex into vibrissa and forelimb areas using ICMS.
  2. Implant a simulating electrode in the vibrissa motor cortex.
  3. Implant EMG electrodes in the forearm.
  4. Sever the buccal and mandibular branches of the facial nerve.
  5. stimulate, and wait for forearm EMG to be elicited by ICMS. Usually occurs! Why? Large horizontal axons in motor cortex? Uncovering of silent synapses, and homeostatic modulation of firing rates?

____References____

[0] Donoghue JP, Suner S, Sanes JN, Dynamic organization of primary motor cortex output to target muscles in adult rats. II. Rapid reorganization following motor nerve lesions.Exp Brain Res 79:3, 492-503 (1990)

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ref: Shuler-2006.03 tags: reward V1 visual cortex timing reinforcement surprising date: 01-03-2012 02:33 gmt revision:4 [3] [2] [1] [0] [head]

PMID-16543459[0] Reward Timing in the Primary Visual Cortex

  • the responses of a substantial fraction of neurons in the primary visual cortex evolve from those that relate solely to the physical attributes of the stimuli to those that accurately predict the timing of reward.. wow!
  • rats. they put goggles on the rats to deliver full-fields retinal illumination for 400ms (isn't this cheating? full field?)
  • recorded from deep layers of V1
  • sensory processing does not seem to be reliable, stable, and reproducible...
  • rewarded only half of the trials, to see if the plasticity was a result of reward delivery or association of stimuli and reward.
  • after 5-7 sessions of training, neurons began to respond to the poststimulus reward time.
  • this was actually independent of reward delivery - only dependent on the time.
  • reward-related activity was only driven by the dominant eye.
  • individual neurons predict reward time quite accurately. (wha?)
  • responses continued even if the animal was no longer doing the task.
  • is this an artifact? of something else? what's going on? the suggest that it could be caused by subthreshold activity due to recurrent connections amplified by dopamine.

____References____

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ref: Merletti-2009.02 tags: surface EMG multielectrode recording technology italy date: 01-03-2012 01:07 gmt revision:2 [1] [0] [head]

PMID-19042063[0] Technology and instrumentation for detection and conditioning of the surface electromyographic signal: state of the art

  • good background & review of surface EMG (sEMG) - noise levels, electrodes, electronics. eg. Instrumentation amplifiers with an input resistance < 100MOhm are not recommended, and the lower the input capacitance, the better: the impedance of a 10pf capacitor at 100hz is 160MOhm.
  • Low and balanced input impedances are required to reduce asymmetric filtering of common-mode power-line noise.

____References____

[0] Merletti R, Botter A, Troiano A, Merlo E, Minetto MA, Technology and instrumentation for detection and conditioning of the surface electromyographic signal: state of the art.Clin Biomech (Bristol, Avon) 24:2, 122-34 (2009 Feb)

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ref: Ming-2009.09 tags: wireless neural recording Ghovanloo NCSU PWM date: 01-03-2012 00:55 gmt revision:3 [2] [1] [0] [head]

IEEE-5333227 (pdf) In vivo testing of a low noise 32-channel wireless neural recording system

  • 32 channels.
  • Unique feature: analog-to-time PWM; digitization ciruitry is hence on the receiver.
  • Even with this, 4.9 uV rms input-referred noise 1Hz-10kHz. Good!
  • Another ASIC.
  • 5.6mW at +- 1.5V, 3.3 x 3.0 mm^2.
  • 1 bit adjustable gain; total gain 67 or 77dB.
  • analog-to-time PWM just uses rail-to-rail comparators, activated by a circulating register.
    • During each comparison, there is no digital transition anywhere on the chip, reducing substrate noise.
  • this 640kHz TDM signal feeds a VCO -> FSK or OOK modulation.
  • Custom receiver. USB.
  • Need to measure THD & input referred noise on mine.
  • -33dB crosstalk.
  • Ghovanloo seems pretty good at citing himself.

____References____

Ming Yin and Seung Bae Lee and Ghovanloo, M. Engineering in Medicine and Biology Society, 2009. EMBC 2009. Annual International Conference of the IEEE 1608 -1611 (2009)

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ref: Atallah-2007.01 tags: striatum skill motor learning VTA substantia nigra basal ganglia reinforcement learning date: 12-31-2011 18:59 gmt revision:3 [2] [1] [0] [head]

PMID-17187065[0] Separate neural substrates for skill learning and performance in the ventral and dorsal striatum.

  • good paper. via SCLin's blog. slightly confusing anatomical terminology.
  • tested in rats, which has a anatomically different basal ganglia system than primates.
  • Rats had to choose which driection in a Y maze based on olfactory cues. Normal rats figure it out in 60 trials.
  • ventral striatum (nucleus accumbens here in rats) connects to the ventral prefrontal cortices (for example, the orbitofrontal cortex)
    • in primates, includes the medial caudate, which has been shown in fMRI to respond to reward prediction error. Neural activity in the caudate is attenuated when a monkey reaches optimal performance.
  • dorsal parts of the striatum (according to web: caudate, putamen, globus pallidus in primates) connect to the dorsal prefrontal and motor cortices
    • (according to them:) this corresponds to the putamen in primates. Activity in the putamen reflects performance but not learning.
    • activity in the putamen is highest after successful learning & accurate performance.
  • used muscimol (GABAa agonist, silences neural activity) and AP-5 (blocks NMDA based plasticity), in each of the target areas.
  • dorsal striatum is involved in performance but not learning
    • Injection of muscimol during acquisition did not impair test performance
    • Injection of muscimol during test phase did impair performance
    • Injection of AP-5 during acquisition had no effect.
    • in acquisition sessions, muscimol blocked instrumental response (performance); but muscimol only has a small effect when it was injected after rats perfected the task.
      • Idea: consistent behavior creates a stimulus-response association in extrastriatal brain areas, e.g. cerebral cortex. That is, the basal ganglia is the reinforcement signal, the cortex learns the association due to feedback-driven behavior? Not part of the habit system, but make and important contribution to goal-directed behavior.
      • This is consistent with the observation that behavior is initially goal driven but is later habitual.
    • Actually, other studies show that plasticity in the dorsal striatum may be detrimental to instrumental learning.
    • The number of neurons that fire just before the execution of a response is larger in the putamen than the caudate.
  • ventral striatum is involved in learning and performance.
    • Injection of AP-5 or muscimol during acquisition (learning behavior) impairs test performance.
    • Injection of AP-5 during test performance has no effect , but muscimol impairs performance.
  • Their data support an actor-director-critic architecture of the striatum:
    • Actor = dorsal striatum; involved in performance, but not in learning them.
    • Director = ventral striatum; quote "it somehow learns the relevant task demands and directs the dorsal striatum to perform the appropriate action plans, but, crucially, it does not train the dorsal striatum"
      • ventrai striatum acts through the orbitofrontal cortex that mantains representations of task-reward contingencies.
      • ventral striatum might also select action selection through it's projections to the substantia nigra.
    • Critic = dopaminergic inputs from the ventral tegmental area and substantia nigra.

____References____

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ref: Shinkman-1974.06 tags: Shinkman Bruce Pfingst operant conditioning visual cortex cat ICMS 1974 stimulation date: 12-29-2011 05:13 gmt revision:4 [3] [2] [1] [0] [head]

PMID-4598035[0] Operant conditioning of single-unit response patterns in visual cortex.

  • In cat V1 -- suprising, this is usually considered to be sensory.
  • implanted bilater tripolar stimulating electrodes aimed at the lateral hypothalamus. These were tested for self-stimulation, and preferred locations/currents were selected for optimal ICS reinforcement.
    • 200 bar presses in 8 minute test.
  • Anesthetized, immobilized, head-restrained, contact-lens focused cats.
  • Back projected stimuli onto a screen 50 cm from eye ; dot, bar, or small spot was effective in triggering patterned response, as with many of these studies.
  • For conditioning: set a threshold at the third quartile (1/4 of trials exceeded threshold); comparator circuit counted the number of spikes during stimulus presentation, and if threshold was exceeded, reinforcing ICS was delivered.
    • Reinforcing ICS started 300ms after visual stimulus and lasted 500ms.
  • Conditioning was deemed successful if the mean trial firing rate for the last 50 conditioned trials had a mean firing rate > 30% larger than the first 50 control trials.
    • While recording some cells, ICS reinforcement was delivered at random as control.
  • Conditioning produced changes within stimulus presentation but not outside.
  • They consider the use of an immobilized subject is a pro -- better control, rules out alternative explanations based on motor feedback.

____References____

[0] Shinkman PG, Bruce CJ, Pfingst BE, Operant conditioning of single-unit response patterns in visual cortex.Science 184:4142, 1194-6 (1974 Jun 14)

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ref: Douglas-1991.01 tags: functional microcircuit cat visual cortex microstimulation date: 12-29-2011 05:12 gmt revision:3 [2] [1] [0] [head]

PMID-1666655[0] A functional microcircuit for cat visual cortex

  • Using in vivo stim and record, They describe what may be a 'cannonical' circuit for the cortex.
  • Not dominated by excitation / inhibition, but rather cell dynamics.
  • Thalamus weaker than poysynaptic inupt from the cortex for excitation.
  • Focuses on Hubel and Wiesel style stuffs. Cats, SUA.
  • Stimulated the geniculate body & observed the response using intracellular electrodes from 102 neurons.
  • Their traces show lots of long-duration inhibition.
  • Probably not relevant to my purposes.

____References____

[0] Douglas RJ, Martin KA, A functional microcircuit for cat visual cortex.J Physiol 440no Issue 735-69 (1991)

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ref: Brown-2008.03 tags: microstimulation recording artifact supression MEA ICMS date: 12-28-2011 20:43 gmt revision:3 [2] [1] [0] [head]

IEEE-4464125 (pdf) Stimulus-Artifact Elimination in a Multi-Electrode System

  • Stimulate and record on the same electrode within 3ms; record on adjacent electrodes within 500us.
  • Target at MEAs, again.
  • Notes that very small charge mismatches of 1% or less, which is common and acceptable in traditional analog circuit designs, generates an artifact that saturates the neural amp signal chain.
  • for stimulating & recording on the same electrode, the the residual charge must be brought down to 1/1e5 the stimulating charge (or less).
  • paper follows upon {833} -- shared author, Blum -- especially in the idea of using active feedback to cancel artifact charge & associated voltage.
  • target the active feedback for keeping all amplifier out of saturation.
  • vary highpass filter poles during artifact supression (!)
  • bias currents of 1fA on the feedback highpass stage. yikes.

Brown EA, Ross JD, Blum RA, Yoonkey N, Wheeler BC, and DeWeerth SP (2008) Stimulus-Artifact Elimination in a Multi-Electrode System. IEEE TRans. Biomed. Circuit Sys. 2. 10-21

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ref: Dagnelie-2008.01 tags: visual BMI prosthesis review Dagnelie date: 12-17-2011 02:25 gmt revision:0 [head]

PMID-18429703 Psychophysical evaluation for visual prosthesis.

  • Visual prostheses are clinical and preclinical trials!
  • cochlear implants function with 16-20 electrodes; retina is 120e6 photoreceptors and 1.2 optic nerve fibers.
  • Argus 2 retinal implant has 60 electrodes. visual information impoverished.
  • In the heyday of prewar German scientific discovery, Foerster (3) established that electrical stimulation of the visual cortex in an awake patient during a neurosurgical intervention produced the percept of dots of light, called phosphenes, and that the location of a phosphene changed with that of the electrical stimulus.
  • people originally thought that loss of the photoreceptors would lead to degradation of the RGCs; this appears not to be true.
  • There is broad consensus that functional vision restoration is predicated on prior visual experience; this is different than cochlera prostheses, which work on congenitally deaf people.
    • Visual development depends on nearly a decade of high-resolution perception, and cannot be emulated later in life through a low-bw prosthesis.
  • There are at the present time at least 20 distinct research groups in at least 8 countries actively engaged in visual prosthesis development.
  • discuss a lot of pre-clinical testing & all the nitty-grity details, e.g. how to make a low res prosthesis work for reading.

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ref: Jimbo-2003.02 tags: MEA microstimulation artifact supression date: 12-17-2011 01:41 gmt revision:2 [1] [0] [head]

PMID-12665038[0] A system for MEA-based multisite stimulation.

  • stimulate and record the same MEA channel.
  • used voltage-control stimulation.
  • very low leakage current switches, DG202CSE, 100Gohm, Maxim, above. non-mechanical = low vibration.
  • switches switch between stimulator and preamp. obvious.
  • uses active shorting post-stimulation to remove residual charge,
  • uses active sample/hold of the preamplifier while the stimulator is connected to the electrodes.
  • adds stimulation pulse to the initial electrode offset (interesting!)

____References____

[0] Jimbo Y, Kasai N, Torimitsu K, Tateno T, Robinson HP, A system for MEA-based multisite stimulation.IEEE Trans Biomed Eng 50:2, 241-8 (2003 Feb)

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ref: Hallworth-2005.07 tags: globus pallidus subthalamic nucelus parkinsons date: 12-07-2011 04:04 gmt revision:1 [0] [head]

PMID-16000620[0] Globus Pallidus Neurons Dynamically Regulate the Activity Pattern of Subthalamic Nucleus Neurons through the Frequency-Dependent Activation of Postsynaptic GABAA and GABAB Receptors

  • in normal animals, STN neurons are spontaneously active, with a resting rate between 10hz and 30hz.
  • during movement, STN neurons display somatotopic, spatiotemporally related changes in activity.
  • in parkinsonian animals, precise sonatotopy is lost, and there is an emergence of correlated, rhythmic activity. STN activity phase-related to tremor has been found in PD patients.
    • this study wants to try to explain why the rhythmic burst activity occurs.
  • one idea: synchronous barages of inhibitory activity results in hyperpolarization-induced high-frequency firing.
  • alternate: GABA_a receptors an mediate a tonic current that profoundly influences postsynaptic excitability. problem: GABA_a receptor antagonists have no effect on STN activity.
  • tonic GABA current was not observed, while there was plenty of GABA mediated IPSPs.
  • strong tetanic simulation of the internal capsule results in STN hyperpolarization followed by bursts of APs. (well then, why do we target the STN in DBS if the oscillations are not it's fault?)

____References____

[0] Hallworth NE, Bevan MD, Globus pallidus neurons dynamically regulate the activity pattern of subthalamic nucleus neurons through the frequency-dependent activation of postsynaptic GABAA and GABAB receptors.J Neurosci 25:27, 6304-15 (2005 Jul 6)

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ref: Carlton-1981.1 tags: visual feedback 1981 error correction movement motor control reaction time date: 12-06-2011 06:35 gmt revision:1 [0] [head]

PMID-6457106 Processing visual feedback information for movement control.

  • Vusual feedback can correct movement within 135ms.
  • Measured this by simply timing the latency from presentation of visual error to initiation of corrective movement.

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ref: Shinkman-1974.06 tags: operant conditioning visual cortex Shinkman date: 11-26-2011 00:40 gmt revision:0 [head]

PMID-4598035 Operant conditioning of single-unit response patterns in visual cortex

  • They successfully conditioned cells in the visual cortex to increase firing response to visual patterns (sensory stimulus).
    • This is conditional response, not conditioning behavior directly.
  • Reinforced using electrical stimulation of the lateral hypothalamus.
    • Optimal reinforcement electrodes were determined via self-stimulation.
  • Immobilized V1 recording appears hardcore. Cats were immobilized but not anesthetized for recording / reinforcement.
  • Delivered fixed ICMS pulse train when threshold number of spikes was exceeded.
  • Data analysis without matlab must have been hard. Actually, the data doesn't look that good, but this may be an artifact of presentation.
  • Controlled for eye movements using a paralytic.

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ref: work-0 tags: machine learning manifold detection subspace segregation linearization spectral clustering date: 10-29-2009 05:16 gmt revision:5 [4] [3] [2] [1] [0] [head]

An interesting field in ML is nonlinear dimensionality reduction - data may appear to be in a high-dimensional space, but mostly lies along a nonlinear lower-dimensional subspace or manifold. (Linear subspaces are easily discovered with PCA or SVD(*)). Dimensionality reduction projects high-dimensional data into a low-dimensional space with minimum information loss -> maximal reconstruction accuracy; nonlinear dim reduction does this (surprise!) using nonlinear mappings. These techniques set out to find the manifold(s):

  • Spectral Clustering
  • Locally Linear Embedding
    • related: The manifold ways of perception
      • Would be interesting to run nonlinear dimensionality reduction algorithms on our data! What sort of space does the motor system inhabit? Would it help with prediction? Am quite sure people have looked at Kohonen maps for this purpose.
    • Random irrelevant thought: I haven't been watching TV lately, but when I do, I find it difficult to recognize otherwise recognizable actors. In real life, I find no difficulty recognizing people, even some whom I don't know personally - is this a data thing (little training data), or mapping thing (not enough time training my TV-not-eyes facial recognition).
  • A Global Geometric Framework for Nonlinear Dimensionality Reduction method:
    • map the points into a graph by connecting each point with a certain number of its neighbors or all neighbors within a certain radius.
    • estimate geodesic distances between all points in the graph by finding the shortest graph connection distance
    • use MDS (multidimensional scaling) to embed the original data into a smaller-dimensional euclidean space while preserving as much of the original geometry.
      • Doesn't look like a terribly fast algorithm!

(*) SVD maps into 'concept space', an interesting interpretation as per Leskovec's lecture presentation.

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ref: Chapin-1999.07 tags: chapin Nicolelis BMI neural net original SUNY rat date: 09-02-2009 23:11 gmt revision:2 [1] [0] [head]

PMID-10404201 Real-time control of a robot arm using simultaneously recorded neurons in the motor cortex.

  • Abstract: To determine whether simultaneously recorded motor cortex neurons can be used for real-time device control, rats were trained to position a robot arm to obtain water by pressing a lever. Mathematical transformations, including neural networks, converted multineuron signals into 'neuronal population functions' that accurately predicted lever trajectory. Next, these functions were electronically converted into real-time signals for robot arm control. After switching to this 'neurorobotic' mode, 4 of 6 animals (those with > 25 task-related neurons) routinely used these brain-derived signals to position the robot arm and obtain water. With continued training in neurorobotic mode, the animals' lever movement diminished or stopped. These results suggest a possible means for movement restoration in paralysis patients.
The basic idea of the experiment. Rat controlled the water lever with a forelimb lever, then later learned to control the water lever directly. They used an artificial neural network to decode the intended movement.

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ref: notes-0 tags: EWH electrosurgery comments date: 03-26-2009 17:18 gmt revision:2 [1] [0] [head]

For the Instructions for use:

  • Section 1.0 -- "... instructions for use of the Electro Surgery ..."
    • Why do we need the decimal point? "Section 1"
  • Section 2.0 -- the figures are labeled 1.1, 1.2, 1.3. Should be 2.1, 2.2, 2.3? Good figures though.
    • Is there some way of cleaning up the figure labeling & numbering in section 5 (and indeed the assembly instructions). It's not bad, but...
  • Section 3.0 -- Maybe make "3.x.x" into bullet points. Numbers are a bit much.
  • Section 4.0 -- The 4.1 is extraneous...
  • Section 5.4 -- Why is the second paragraph text gray?
  • Section 5.5 -- "Wait two minutes for the power resistor to cool before repeating step 5.4". (Might as well tell them why they are waiting, gives them more reason to do so).
  • Section 5.7 -- Remind the user to wait some time for the power resistors to cool before trying different power settings. At lower powers, they will not have to wait too long; higher power will require longer wait time. In the future might want to put a thermsistor/resettable poly fuse or the like in there to thermally protect the device. Or one of the bimetal heat switches that they use in hair dryers; I'd imagine that they are cheap.
  • I'm not very familiar with ESU devices, but is there a possibility to see varying power levels within the 4-second evaluation period? Would this be important to note?

For the assembly instructions:

  • Section 2.0 -- You can probably get some images of the resistors off digikey :-)
    • Also, don't need to number "2.x" all of the components. One number in that table should be enough.
    • Separate column for device quantity would aid clarity.
  • Section 3.0 -- Are numbers needed for this short list?
  • Section 4.0 -- Ditto. Maybe bullets would be clearer. As for the grounded bench, perhaps should explain that static electricity can damage the diodes.
  • Section 5.0 --
    • Why make the user refer to the appendix for the resistor color codes? Just take a picture of the finished board, with all but the resistors masked out or lightened in photoshop, so the assembler can see what goes where. Or some other clear figure.
    • Tools and materials should not get its own column; put that in a row or bullet before the table. Maybe have a bullet point: "Components needed: R8, R7, R6..." This lets you make the pictures larger.
  • Section 5.2 -- Figure 3 - exactly! good figure.
    • Might as well put the diode numbers and values in the table. There is enough space below the first instruction bullet point.
  • Section 5.3 - 5.6 -- looks good.
  • Section 5.7 -- I would have to try this; it seems that most of the creases are intuitively obvious. Again, don't see the need for the gray text, though. The figures are good & illustrative.
  • Section 5.9 -- Would it be easier to apply the labels before folding, that way it is easy to apply even and firm pressure? I'm extrapolating here, don't know.
  • Appendix A -- You can hold LEDs or other components flush by bending the leads out after insertion. Re-melting & pushing the leads in sometimes results in bad solder joints. Otherwise good.

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ref: Mehta-2007.01 tags: hippocampus visual cortex wilson replay sleep learning states date: 03-09-2009 18:53 gmt revision:1 [0] [head]

PMID-17189946[0] Cortico-hippocampal interaction during up-down states and memory consolidation.

  • (from the associated review) Good pictorial description of how the hippocampus may impinge order upon the cortex:
    • During sleep the cortex is spontaneously and randomly active. Hippocampal activity is similarly disorganized.
    • During waking, the mouse/rat moves about in the environment, activating a sequence of place cells. The weights of the associated place cells are modified to reflect this sequence.
    • When the rat falls back to sleep, the hippocampus is still not random, and replays a compressed copy of the day's events to the cortex, which can then (and with other help, eg. ACh), learn/consolidate it.
  • see [1].

____References____

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ref: Ji-2007.01 tags: hippocampus visual cortex wilson replay sleep date: 03-09-2009 18:48 gmt revision:3 [2] [1] [0] [head]

PMID-17173043[0] Coordinated memory replay in the visual cortex and hippocampus during sleep.

  • EEG from Layer 5 of the visual cortex.
  • used tetrodes.
  • rats were trained to alternate loops in a figure-8 maze to get at food.
  • the walls of the maze were lined with high-contrast cues.
  • data for correlated activity between ctx and hippocampus weak - they just show that the frame ('up' period in cellular activity) start & end between the two regions are correlated. No surprise - they are in the same brain after all!
  • Found that cells in the deep visual cortex (V1 & V2) had localized firing fields. Rat vision is geared for navigation? (mostly?)
  • From this, they could show offline replay of the same sequence; these offline sequences were compressed by about 5-10.
    • shuffle tests on the replayed frames look pretty good - respectable degree of significance here.
    • Aside: possibly some of the noise of the recordings is reflective not of the noise of the system, but the noise / high dimensionality of the sensory input driving the visual ctx.
  • Also found some visual and some hippocampal cells that replayed sequences simultaneously; shuffle test here looks ok too.
  • picture from associated review, {692}

____References____

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ref: bookmark-0 tags: blog resume inspire layout design date: 03-02-2009 16:42 gmt revision:1 [0] [head]

http://10ch.wordpress.com/2009/02/07/sometimes-i-go-big/

  • great examples of resumes, and the right attitude to go with them.
  • inforgraphic resume - cool!

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ref: Recanzone-1993.01 tags: plasticity cortex learning auditory owl monkeys SUA date: 10-06-2008 22:46 gmt revision:1 [0] [head]

PMID-8423485[0] Plasticity in the frequency representation of primary auditory cortex following discrimination training in adult owl monkeys

  • Measured tonotopic organization (hence plasticity) in the owl monkey auditory cortex following training on a frequency discrimination task.
  • improvement in performance correlates with an improvement in neuronal tuning.
  • two controls:
    • monkeys that were engaged in a tactile discrimination task
    • monkeys that received the same auditory stimuli but had no reason to attend to it
  • lots of delicious behavior graphs

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ref: Isoda-2007.02 tags: SMA saccade basal_forebrain executive function 2007 microstimulation SUA cortex sclin date: 10-03-2008 17:12 gmt revision:2 [1] [0] [head]

PMID-17237780[0] Switching from automatic to controlled action by monkey medial frontal cortex.

  • SCLIN's blog entry
  • task: two monkeys were trained to saccade to one of two targets, left/right pink/yellow. the choice was cued by the color of the central fixation target; when it changed, they should saccade to the same-colored target.
    • usually, the saccade direction remained the same; sometimes, it switched.
    • the switch could either occur to the same side as the SUA recording (ipsilateral) or to the opposite (contralateral).
  • found cells in the pre-SMA that would fire when the monkey had to change his adapted behavior
    • both cells that increased firing upon an ipsi-switch and contra-switch
  • microstimulated in SMA, and increased the number of correct trials!
    • 60ua, 0.2ms, cathodal only,
    • design: stimulation simulated adaptive-response related activity in a slightly advanced manner
    • don't actually have that many trials of this. humm?
  • they also did some go-nogo (no saccade) work, in which there were neurons responsive to inhibiting as well as facilitating saccades on both sides.
    • not a hell of a lot of neurons here nor trials, either - but i guess proper statistical design obviates the need for this.
  • I think if you recast this in tems of reward expectation it will make more sense and be less magical.
  • would like to do shadlen-similar type stuff in the STN
questions
  1. how long did it take to train the monkeys to do this?
  2. what part of the nervous system looked at the planned action with visual context, and realized that the normal habitual basal-ganglia output would be wrong?
    1. probably the whole brain is involved in this.
    2. hypothetical path of error trials: visual system -> cortico-cortico projections + context activation -> preparatory motor activity -> basal ganglia + visual context (is there anatomical basis for this?) -> activation of some region that detects the motor plan is unlikely to result in reward -> SMA?

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ref: Corlett-2007.09 tags: delusions pFC substantia nigra date: 09-23-2008 06:15 gmt revision:0 [head]

PMID-17690132 Disrupted prediction-error signal in psychosis: evidence for an associative account of delusions.

  • Hypothesis: the creation and maintenance of psychotic or delusional beliefs is caused by (or causally related to) malfunction in the predictive error circuitry in the brain. (namely, the prefrontal cortex, substantia nigra, and striatum).
  • Previous studies have shown that administering Ketamine, a dissociative drug that can cause delusions, effects this same pathway.
  • The authors tested the hypothesis by training control and psychotic subjects in an associative task: subjects had to determine if a fictitious patient would be allergic to a meal given example meals and resulting allergic reaction.
  • Both sets had about the same behavioral performance; however, activation of the prefrontal cortex, substantia nigra, and left striatum was less in the psychotic (some drug treated) subjects. This comparison of activation was measured between control trials (no prediction error) and violation trials (prediction violated) as well as unovershadowing (a and b causes allergy, but a or b separately do not)

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ref: bookmark-0 tags: murder cerebrum PET scan Adrian Raine violence prefrontal corpus callosum amygdala activation brain scan date: 08-29-2008 14:32 gmt revision:0 [head]

http://www.dana.org/news/cerebrum/detail.aspx?id=3066 -- great article, with a well thought out, delicate treatment of the ethical/moral/ legal issues created by the interaction between the biological roots of violence (or knowlege thereof) and legal / social systems. He posits that there must be a continuum between ratinoal free will and irrational, impulsive violent behavior, with people biased to both by genetics, development, traumatic head injury, and substance abuse (among others).

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ref: bookmark-0 tags: memory supermemo leraning psychology Hermann Ebbinghaus date: 05-08-2008 15:25 gmt revision:0 [head]

http://www.wired.com/medtech/health/magazine/16-05/ff_wozniak -- wonderful article, well written. Leaves you with a sense of Piotr Wozniak (SuperMemo's inventor) crazy, slightly surreal, impassioned, purposeful, but self-regressive (and hence fundamentally stationary) life.

  • Quote: SuperMemo was like a genie that granted Wozniak a wish: unprecedented power to remember. But the value of what he remembered depended crucially on what he studied, and what he studied depended on his goals, and the selection of his goals rested upon the efficient acquisition of knowledge, in a regressive function that propelled him relentlessly along the path he had chosen.
  • http://www.wired.com/images/article/magazine/1605/ff_wozniak_graph_f.jpg
  • Quote: This should lead to radically improved intelligence and creativity. The only cost: turning your back on every convention of social life.

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ref: notes-0 tags: DNA transfection yasuda experiment8 date: 03-17-2008 20:11 gmt revision:2 [1] [0] [head]

"

dishdnanameconc ug/ululug
1HM8-46His-mGFP-stop-C1-20.140.70.1
2HM8-46His-mGFP-stop-C1-20.143.60.5
5HM8-46His-mGFP-stop-C1-20.140.70.1
"HM8-47His-mCherry-stop-C10.120.830.1
6HM8-46His-mGFP-stop-C1-20.143.60.5
"HM8-47His-mCherry-stop-C10.120.830.1
7HM8-46His-mGFP-stop-C1-20.140.70.1
"HM8-47His-mCherry-stop-C10.124.20.5
8HM8-46His-mGFP-stop-C1-20.143.60.5
"HM8-47His-mCherry-stop-C10.124.20.5

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ref: bookmark-0 tags: software visualization C++ sgv date: 03-17-2008 19:44 gmt revision:9 [8] [7] [6] [5] [4] [3] [head]

http://www.sgvsarc.com/demo.htm

  • looks like a good way to understand a large amount of code quickly. I've been waiting for a product like this for some time now!
    • I secretly hoped, given the name, that it would produce SVG files. It turns out otherwise: I'm just dyslexic :)

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ref: bookmark-0 tags: RF penetration tissue 1978 date: 07-24-2007 04:15 gmt revision:2 [1] [0] [head]

http://hardm.ath.cx:88/pdf/RFpenetrationInTissue.pdf

  • from the perspective of NMR imaging.
  • gives the penetration depths & phase-shifts for RF waves from 1 - 100Mhz. I can obly assume that it is much worse for 400Mhz and 2.4Ghz.
    • that said, Zarlink's MICS transceiver works from the GI tract at 400mhz with low power, suggesting that the attenuation can't be too too great.
  • includes equations used to derive these figures.
  • document describing how various antenna types are effected by biological tissue, e.g. a human head.

even more interesting: wireless brain machine interface

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ref: Sabelli-1976.08 tags: anatomy of the spinal cord interneurons pyramidal tract commissure reflexes date: 04-23-2007 05:12 gmt revision:1 [0] [head]

Anatomy of the spinal cord

  • wow! detailed!!
  • the spinal cord is remarkably complex (of course, considering how old it is and how important it is for structuring movement and locomotion..well..most animals)
  • there is a lot of well-organized circuitry in the spinal cord mediating adaptive phenomena and reflexes like the clasp knife reflex (upper motoneuron disease where the resistance to flexion abruptly melts away when the joint is fully flexed)

____References____

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ref: Ashe-1994.12 tags: Georgoplous motor control M1 S1 SUA electrophysiology 2D date: 04-09-2007 20:27 gmt revision:2 [1] [0] [head]

PMID-7703686[0] Movement parameters and neural activity in motor cortex and area 5

  • 290 cells in the motor cortex and 207 cells in area 5 (S1)
  • median R^2 = 0.581 & 0.530 in motor cortex
  • most prominent representation of target direction; least prominent representation of acceleration. (though statistically significant correlations were observed for all behavioral parameters)

Duke does not have online access to the article :(

____References____

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ref: Sergio-2003.01 tags: M1 isometric force posture direction SUA Kalaska date: 04-09-2007 15:22 gmt revision:1 [0] [head]

PMID-12522173[0] Systematic changes in motor cortex cell activity with arm posture during directional isometric force generation.

  • isometric joystick was positioned at 5-9 different locations in a plane in the monkey's workspace.
  • discharge of all cells varied with position and force.
    • Cell directional tuning tended to shift systematically with hand location even though the direction of static force output at the hand remained constant
      • would this be true if the forces were directed in muscle coordinates?
  • "provides further evidence that MI contributes to the transformation between extrinsic and intrinsic representations of motor output during isometric force production."

____References____

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ref: Taira-1996.06 tags: 3D Georgopoulos SUA M1 force motor control direction tuning date: 04-09-2007 15:16 gmt revision:1 [0] [head]

PMID-8817266[0] On the relations between single cell activity in the motor cortex and the direction and magnitude of three-dimensional static isometric force.

  • 3D isometric joystick.
  • stepwise multiple linear regression.
  • direction of force is a signal especially prominent in the motor cortex.
    • the pure directional effect was 1.8 times more prevalent in the cells than in the muscles studied (!)

____References____

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ref: Wahnoun-2004.01 tags: BMI population_vector neural selection Brown 3D arizona ASU date: 04-06-2007 23:28 gmt revision:3 [2] [1] [0] [head]

PMID-17271333[0] Neuron selection and visual training for population vector based cortical control.

  • M1 and Pmd (not visual areas), bilateral.
  • a series of experiments designed to parameterize a cortical control algorithm without an animal having to move its arm.
  • a highly motivated animal observes as the computer drives a cursor move towards a set of targets once each in a center-out task.
    • how motivated? how did they do this? (primate working for its daily water rations)
  • I do not think this is the way to go. it is better to stimulate in the proper afferents and let the brain learn the control algorithm, the same as when a baby learns to crawl.
    • however, the method described here may be a good way to bootstrap., definitely.
  • want to generate an algorithm that 'tunes-up' control with a few tens of neurons, not hundreds as Miguel estimates.
  • estimate the tuning from 12 seconds of visual following (1.5 seconds per each of the 8 corners of a cube)
  • optimize over the subset of neurons (by dropping them) & computing the individual residual error.
  • their paper seems to be more of an analysis of this neuron-removal method.
  • neurons seem to maintain their tuning between visual following and brain-control.
  • they never actually did brain control

PMID-16705272[1] Selection and parameterization of cortical neurons for neuroprosthetic control

  • here they actually did neuroprosthetic control.
  • most units add noise to the control signal, a few actually improve it -> they emphasize cautious unit selection leaning to simpler computational/electrical systems.
  • point out that the idea of using chronically recorded neural signals has a very long history.. [2,3,4,5] [6] etc.
  • look like it took the monkeys about 1.6-1.8 seconds to reach the target.
    • minimum summed path length / distance to target = 3.5. is that good?

____References____

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ref: Fu-1993.11 tags: premotor M1 PMd PMv SUA date: 04-05-2007 17:12 gmt revision:0 [head]

PMID-8294972[0] Neuronal specification of direction and distance during reaching movements in the superior precentral premotor area and primary motor cortex of monkeys.

  • key thing: distance to target is represented in the motor & premotor corticies.

____References____

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ref: Amirikian-2000.01 tags: Georgopulos directional tuning motor cortex SUA electrophysiology date: 04-05-2007 16:34 gmt revision:2 [1] [0] [head]

PMID-10678534[0] Directional tuning profiles of motor cortical cells

  • trained the monkeys to move to 20 targets in a horizontal plane
    • the larger number of targets allowed a more accurate estimation of the tuning properties of the cells
    • measured tuning based on the spike count during movement.
  • typical r^2 = 0.7 for a modified cosine fit

____References____

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ref: work notes-0 tags: web stimulator SUNY ICMS python webinterface project date: 03-26-2007 04:26 gmt revision:1 [0] [head]

we are proud of this :)

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ref: Pollak-1993.01 tags: DBS STN subthalamic nucleus original 1993 Benabid date: 03-12-2007 04:58 gmt revision:2 [1] [0] [head]

PMID-8235208[] Effects of the stimulation of the subthalamic nucleus in Parkinson disease

  • the original study! (in french:)
  • even back then, they used a quadripolar medtronic stimulating electrode w/ stimulation frequency of 130Hz.
  • how far have we come? not too far.

____References____

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ref: engineering notes-0 tags: homopolar generator motor superconducting magnet date: 03-09-2007 14:39 gmt revision:0 [head]

http://hardm.ath.cx:88/pdf/homopolar.pdf

  • the magnets are energized in 'opposite directions - forcing the field lines to go normal to the rotar.
  • still need brushes - perhaps there is no way to avoid them in a homopolar generator.

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ref: neuro notes-0 tags: SNr SNc substantia nigra anatomy tracing date: 02-06-2007 05:40 gmt revision:0 [head]

Patterns of axonal branching of neurons of the substantia nigra pars reticulata and pars lateralis in the rat.

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ref: Teich-1997.03 tags: fractal LGN RGC electrophysiology SUA fano_factor date: 02-05-2007 19:00 gmt revision:0 [head]

PMID-9058948[0] Fractal character of the neural spike train in the visual system of the cat

  • excellent description of several analyses of point-process spike trains (here RGC and LGN cells): interevent-interval histogram, rescaled range analysis, the event-number histogram, the Fano factor, the Allan factor, and the periodogram.

http://hardcarve.com/wikipic/Teich1997_fanofactor.gif

____References____

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ref: Vyssotski-2006.02 tags: neurologger neural_recording recording_technology EEG SUA LFP electrical engineering date: 02-05-2007 06:21 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

PMID-16236777[0] Miniature neurologgers for flying pigeons: multichannel EEG and action and field potentials in combination with GPS recording.

Recording neuronal activity of animals moving through their natural habitat is difficult to achieve by means of conventional radiotelemetry. This illustration shows a new approach, exemplified by a homing pigeon carrying both a small GPS path recorder and a miniaturized action and field potential logger (“neurologger”), the entire assembly weighing maximally 35 g, a load carried easily by a pigeon over a distance of up to 50 km. Before release at a distant location, the devices are activated and store both positional and neuronal activity data during the entire flight. On return to the loft, all data are downloaded and can be analyzed using software for path analysis and electrical brain activity. Thus single unit activity or EEG patterns can be matched to the flight path superimposed on topographical maps. Such neurologgers may also be useful for a variety of studies using unrestrained laboratory animals in different environments or test apparatuses. The prototype on the hand-held pigeon records and stores EEG simultaneously from eight channels up to 47 h, or single unit activity from two channels during 9 h, but the number of channels can be increased without much gain in weight by sandwiching several of these devices. Further miniaturization can be expected. For details, see Vyssotski AL, Serkov AN, Itskov PM, Dell Omo G, Latanov AV, Wolfer DP, and Lipp H-P. Miniature neurologgers for flying pigeons: multichannel EEG and action and field potentials in combination with GPS recording. [1]

____References____

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ref: Wichmann-1999.04 tags: parkinsons basal ganglia substantia nigra date: 0-0-2007 0:0 revision:0 [head]

PMID-10323285 Comparison of MPTP-induced changes in spontaneous neuronal discharge in the internal pallidal segment and in the substania nigra pars reticulata

  • putamen = motor portion of the striatum.
  • basal ganglia output is directed toward the ventral anterior, ventrolateral, and centromedial nuclei of the thalamus, which, in turn, project back to the cortex. Plus, the output of the basal ganglia project to the cortex.
  • MPTP induces excessive 3-8 Hz bursts in the GPi (e.g. correlated with tremor).

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ref: bookmark-0 tags: neuroanatomy pulvinar thalamus superior colliculus image gray brainstem date: 0-0-2007 0:0 revision:0 [head]

http://en.wikipedia.org/wiki/Image:Gray719.png --great, very useful!

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ref: notes-0 tags: insular cortex anterior cingulate spindle neurons date: 0-0-2007 0:0 revision:0 [head]

spindle neurons are found in the insular cortex as well as the anterior cingulate cortex, but only, apparently, in great apes. Activity in the insular cortex has been found to be correlated to feeling empathy.

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ref: notes-0 tags: LSD rhesus monkeys date: 0-0-2007 0:0 revision:0 [head]

http://hardm.ath.cx:88/pdf/LSDRhesusMonkeys.pdf

  • monkeys had a sucking behavior after large doses
  • human babies have synestesia
  • perhaps LSD has some endogenous equivalent found in babies?

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ref: bookmark-0 tags: debian linux sarge apache2 subversion install ssl date: 0-0-2006 0:0 revision:0 [head]

http://mattl.co.uk/apache2subversiondebianhowto.html pretty good. SSL and subversion seems to cause problems with apache2 on this 'unstable' Debian build - it complains of a BAD MAC header after a deterministic number of bytes are transmitted. Therefore I moved to port 80 from 443.

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ref: bookmark-0 tags: neural_networks machine_learning matlab toolbox supervised_learning PCA perceptron SOM EM date: 0-0-2006 0:0 revision:0 [head]

http://www.ncrg.aston.ac.uk/netlab/index.php n.b. kinda old. (or does that just mean well established?)

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ref: bookmark-0 tags: brazilian consulate miami visa date: 0-0-2006 0:0 revision:0 [head]

http://www.brazilmiami.org/consulado/English/visas/TOURIST%20VISA.htm

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ref: bookmark-0 tags: microdrilling surgery craniotomy impedance date: 0-0-2006 0:0 revision:0 [head]

http://www.pathscientific.com/products.html

Pathformer is an electrosurgical hand-held meidcal device that cuts holes in nails and skin. It operates on mesoscissioning technology, cutting the nail/skin with a microcutting tool, using skin impedance as a feedback for stopping the cutting intervention. Pathformer is approved by FDA for creating holes in nails for treating subungual hematoma (black toe).

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ref: notes, bookmark-0 tags: spikes action_potentials neurons subthreshold depolarization c.elegans date: 0-0-2006 0:0 revision:0 [head]

"Millisecond-timescale, genetically targeted optical control of neural activity" http://www.nature.com/neuro/journal/v8/n9/full/nn1525.html

what they did:

  • expressed ChR2 receptor in cultured hippocampal neurons.
  • ChR2 is a rapidly-gated light-sensitive cation channel recently isolated from unicellular green alga
  • cells were transfected via lentivirus
  • caused spiking in cells by exposing them to 5-15ms flashes of blue light.
  • stimulation was reliable to 30hz
  • stimulated spikes had low jitter - 2ms or so.
  • light stimulation protocol was robust across different neurons.
  • expression of the light-gated channel did not alter the properties of the neurons or their health etc.
  • they think it might be applicable to in-vivo mamalian studies!
  • Subthreshold!
    • for many cellular and systems neuroscience processes subthreshold depolarizations convey physiologically significant information.
    • the neurons in c.elegans do not spike!
    • subthreshold depolarizations are potent for activating synapes-to-nucleus signaling
    • the relative timing of subthreshold and suprathreshold depolarizations can determine the direction of synaptic plasticity.
    • subthreshold depolarizations operate in the more linear regime of membrane voltage