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

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

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

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

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

[0] Shink E, Bevan MD, Bolam JP, Smith Y, The subthalamic nucleus and the external pallidum: two tightly interconnected structures that control the output of the basal ganglia in the monkey.Neuroscience 73:2, 335-57 (1996 Jul)

[0] Isoda M, Hikosaka O, Role for subthalamic nucleus neurons in switching from automatic to controlled eye movement.J Neurosci 28:28, 7209-18 (2008 Jul 9)

[0] Elble RJ, Central mechanisms of tremor.J Clin Neurophysiol 13:2, 133-44 (1996 Mar)

[0] Bar-Gad I, Morris G, Bergman H, Information processing, dimensionality reduction and reinforcement learning in the basal ganglia.Prog Neurobiol 71:6, 439-73 (2003 Dec)

[0] Evarts EV, Relation of pyramidal tract activity to force exerted during voluntary movement.J Neurophysiol 31:1, 14-27 (1968 Jan)

[0] Mohseni P, Najafi K, Eliades SJ, Wang X, Wireless multichannel biopotential recording using an integrated FM telemetry circuit.IEEE Trans Neural Syst Rehabil Eng 13:3, 263-71 (2005 Sep)

[0] Mojarradi M, Binkley D, Blalock B, Andersen R, Ulshoefer N, Johnson T, Del Castillo L, A miniaturized neuroprosthesis suitable for implantation into the brain.IEEE Trans Neural Syst Rehabil Eng 11:1, 38-42 (2003 Mar)

[0] Santhanam G, Linderman MD, Gilja V, Afshar A, Ryu SI, Meng TH, Shenoy KV, HermesB: a continuous neural recording system for freely behaving primates.IEEE Trans Biomed Eng 54:11, 2037-50 (2007 Nov)

[0] Carmena JM, Lebedev MA, Crist RE, O'Doherty JE, Santucci DM, Dimitrov DF, Patil PG, Henriquez CS, Nicolelis MA, Learning to control a brain-machine interface for reaching and grasping by primates.PLoS Biol 1:2, E42 (2003 Nov)

[0] Kipke DR, Vetter RJ, Williams JC, Hetke JF, Silicon-substrate intracortical microelectrode arrays for long-term recording of neuronal spike activity in cerebral cortex.IEEE Trans Neural Syst Rehabil Eng 11:2, 151-5 (2003 Jun)

[0] Fetz EE, Baker MA, Operantly conditioned patterns on precentral unit activity and correlated responses in adjacent cells and contralateral muscles.J Neurophysiol 36:2, 179-204 (1973 Mar)

[0] Fetz EE, Operant conditioning of cortical unit activity.Science 163:870, 955-8 (1969 Feb 28)[1] Fetz EE, Finocchio DV, Operant conditioning of specific patterns of neural and muscular activity.Science 174:7, 431-5 (1971 Oct 22)[2] Fetz EE, Finocchio DV, Operant conditioning of isolated activity in specific muscles and precentral cells.Brain Res 40:1, 19-23 (1972 May 12)

[0] Porada I, Bondar I, Spatz WB, Kruger J, Rabbit and monkey visual cortex: more than a year of recording with up to 64 microelectrodes.J Neurosci Methods 95:1, 13-28 (2000 Jan 31)

[0] BASMAJIAN JV, Control and training of individual motor units.Science 141no Issue 440-1 (1963 Aug 2)

[0] Nicolelis MA, Dimitrov D, Carmena JM, Crist R, Lehew G, Kralik JD, Wise SP, Chronic, multisite, multielectrode recordings in macaque monkeys.Proc Natl Acad Sci U S A 100:19, 11041-6 (2003 Sep 16)

[0] Evarts EV, Activity of pyramidal tract neurons during postural fixation.J Neurophysiol 32:3, 375-85 (1969 May)[1] Evarts EV, Relation of pyramidal tract activity to force exerted during voluntary movement.J Neurophysiol 31:1, 14-27 (1968 Jan)

[0] Fetz EE, Perlmutter SI, Prut Y, Functions of mammalian spinal interneurons during movement.Curr Opin Neurobiol 10:6, 699-707 (2000 Dec)

[0] Sodagar AM, Wise KD, Najafi K, A fully integrated mixed-signal neural processor for implantable multichannel cortical recording.IEEE Trans Biomed Eng 54:6 Pt 1, 1075-88 (2007 Jun)

[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] Moran DW, Schwartz AB, Motor cortical representation of speed and direction during reaching.J Neurophysiol 82:5, 2676-92 (1999 Nov)

[0] Csicsvari J, Henze DA, Jamieson B, Harris KD, Sirota A, Bartho P, Wise KD, Buzsaki G, Massively parallel recording of unit and local field potentials with silicon-based electrodes.J Neurophysiol 90:2, 1314-23 (2003 Aug)

[0] Williams JC, Rennaker RL, Kipke DR, Long-term neural recording characteristics of wire microelectrode arrays implanted in cerebral cortex.Brain Res Brain Res Protoc 4:3, 303-13 (1999 Dec)

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

[0] Sergio LE, Kalaska JF, Systematic changes in directional tuning of motor cortex cell activity with hand location in the workspace during generation of static isometric forces in constant spatial directions.J Neurophysiol 78:2, 1170-4 (1997 Aug)

[0] Cheney PD, Fetz EE, Functional classes of primate corticomotoneuronal cells and their relation to active force.J Neurophysiol 44:4, 773-91 (1980 Oct)

[0] Fu QG, Flament D, Coltz JD, Ebner TJ, Temporal encoding of movement kinematics in the discharge of primate primary motor and premotor neurons.J Neurophysiol 73:2, 836-54 (1995 Feb)

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ref: -2019 tags: neuromorphic optical computing date: 06-19-2019 14:47 gmt revision:1 [0] [head]

Large-Scale Optical Neural Networks based on Photoelectric Multiplication

  • Critical idea: use coherent homodyne detection, and quantum photoelectric multiplication for the MACs.
    • That is, E-fields from coherent light multiplies rather than adds within a (logarithmic) photodiode detector.
    • Other lit suggests rather limited SNR for this effect -- 11db.
  • Hence need EO modulators and OE detectors followed by nonlinearity etc.
  • Pure theory, suggests that you can compute with as few as 10's of photons per MAC -- or less! Near Landauer's limit.

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ref: -2016 tags: fluorescent proteins photobleaching quantum yield piston GFP date: 06-19-2019 14:33 gmt revision:0 [head]

PMID-27240257 Quantitative assessment of fluorescent proteins.

  • Cranfill PJ1,2, Sell BR1, Baird MA1, Allen JR1, Lavagnino Z2,3, de Gruiter HM4, Kremers GJ4, Davidson MW1, Ustione A2,3, Piston DW
  • Model bleaching as log(F)=αlog(P)+clog(F) = -\alpha log(P) + c or k bleach=bI αk_{bleach} = b I^{\alpha} where F is the fluorescence intensity, P is the illumination power, and b and c are constants.
    • Most fluorescent proteins have α\alpha > 1, which means superlinear photobleaching -- more power, bleaches faster.
  • Catalog the degree to which each protein tends to form aggregates by tagging to the ER and measuring ER morphology. Fairly thorough -- 10k cells each FP.

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ref: -2017 tags: neuromorphic optical computing nanophotonics date: 06-17-2019 14:46 gmt revision:5 [4] [3] [2] [1] [0] [head]

Progress in neuromorphic photonics

  • Similar idea as what I had -- use lasers as the optical nonlinearity.
    • They add to this the idea of WDM and 'MRR' (micro-ring resonator) weight bank -- they don't talk about the ability to change the weihts, just specify them with some precision.
  • Definitely makes the case that III-V semiconductor integrated photonic systems have the capability, in MMACs/mm^2/pj, to exceed silicon.

See also :

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ref: -2013 tags: microscopy space bandwidth product imaging resolution UCSF date: 06-17-2019 14:45 gmt revision:0 [head]

How much information does your microscope transmit?

  • Typical objectives 1x - 5x, about 200 Mpix!

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ref: -2012 tags: phase change materials neuromorphic computing synapses STDP date: 06-13-2019 21:19 gmt revision:3 [2] [1] [0] [head]

Nanoelectronic Programmable Synapses Based on Phase Change Materials for Brain-Inspired Computing

  • Here, we report a new nanoscale electronic synapse based on technologically mature phase change materials employed in optical data storage and nonvolatile memory applications.
  • We utilize continuous resistance transitions in phase change materials to mimic the analog nature of biological synapses, enabling the implementation of a synaptic learning rule.
  • We demonstrate different forms of spike-timing-dependent plasticity using the same nanoscale synapse with picojoule level energy consumption.
  • Again uses GST germanium-antimony-tellurium alloy.
  • 50pJ to reset (depress) the synapse, 0.675pJ to potentiate.
    • Reducing the size will linearly decrease this current.
  • Synapse resistance changes from 200k to 2M approx.

See also: Experimental Demonstration and Tolerancing of a Large-Scale Neural Network (165 000 Synapses) Using Phase-Change Memory as the Synaptic Weight Element

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ref: -2019 tags: optical neural networks spiking phase change material learning date: 06-01-2019 19:00 gmt revision:4 [3] [2] [1] [0] [head]

All-optical spiking neurosynaptic networks with self-learning capabilities

  • J. Feldmann, N. Youngblood, C. D. Wright, H. Bhaskaran & W. H. P. Pernice
  • Idea: use phase-change material to either block or pass the light in waveguides.
    • In this case, they used GST -- germanium-antimony-tellurium. This material is less reflective in the amorphous phase, which can be reached by heating to ~150C and rapidly quenching. It is more reflective in the crystalline phase, which occurs on annealing.
  • This is used for both plastic synapses (phase change driven by the intensity of the light) and the nonlinear output of optical neurons (via a ring resonator).
  • Uses optical resonators with very high Q factors to couple different wavelengths of light into the 'dendrite'.
  • Ring resonator on the output: to match the polarity of the phase-change material. Is this for reset? Storing light until trigger?
  • Were able to get correlative-like or hebbian learning (which I suppose is not dissimilar from really slow photographic film, just re-branded, and most importantly with nonlinear feedback.)
  • Issue: every weight needs a different source wavelength! Hence they have not demonstrated a multi-layer network.
  • Previous paper: All-optical nonlinear activation function for photonic neural networks
    • Only 3db and 7db extinction ratios for induced transparency and inverse saturation

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ref: -0 tags: synaptic plasticity 2-photon imaging inhibition excitation spines dendrites synapses 2p date: 05-31-2019 23:02 gmt revision:2 [1] [0] [head]

PMID-22542188 Clustered dynamics of inhibitory synapses and dendritic spines in the adult neocortex.

  • Cre-recombinase-dependent labeling of postsynapitc scaffolding via Gephryn-Teal fluorophore fusion.
  • Also added Cre-eYFP to lavel the neurons
  • Electroporated in utero e16 mice.
    • Low concentration of Cre, high concentrations of Gephryn-Teal and Cre-eYFP constructs to attain sparse labeling.
  • Located the same dendrite imaged in-vivo in fixed tissue - !! - using serial-section electron microscopy.
  • 2230 dendritic spines and 1211 inhibitory synapses from 83 dendritic segments in 14 cells of 6 animals.
  • Some spines had inhibitory synapses on them -- 0.7 / 10um, vs 4.4 / 10um dendrite for excitatory spines. ~ 1.7 inhibitory
  • Suggest that the data support the idea that inhibitory inputs maybe gating excitation.
  • Furthermore, co-inervated spines are stable, both during mormal experience and during monocular deprivation.
  • Monocular deprivation induces a pronounced loss of inhibitory synapses in binocular cortex.

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ref: -0 tags: Na Ji 2p two photon fluorescent imaging pulse splitting damage bleaching date: 05-31-2019 19:55 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-18204458 High-speed, low-photodamage nonlinear imaging using passive pulse splitters

  • Core idea: take a single pulse and spread it out to N=2 kN= 2^k pulses using reflections and delay lines.
  • Assume two optical processes, signal SI αS \propto I^{\alpha} and photobleaching/damage DI βD \propto I^{\beta} , β>α>1\beta \gt \alpha \gt 1
  • Then an NN pulse splitter requires N 11/αN^{1-1/\alpha} greater average power but reduces the damage by N 1β/α.N^{1-\beta/\alpha}.
  • At constant signal, the same NN pulse splitter requires N\sqrt{N} more power, consistent with two photon excitation (proportional to the square of the intensity: N pulses of N/N\sqrt{N}/N intensity, 1/N per pulse fluorescence, Σ1\Sigma \rightarrow 1 overall fluorescence.)
  • This allows for shorter dwell times, higher power at the sample, lower damage, slower photobleaching, and better SNR for fluorescently labeled slices.
  • Examine the list of references too, e.g. "Multiphoton multifocal microscopy exploiting a diffractive optical element" (2003)

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ref: -0 tags: phosphorescence fluorescence magnetic imaging slicing adam cohen date: 05-29-2019 19:41 gmt revision:8 [7] [6] [5] [4] [3] [2] [head]

A friend postulated using the triplet state phosphorescence as a magnetically-modulatable dye. E.g. magnetically slice a scattering biological sample, rather than slicing optically (light sheet, 2p) or mechanically. After a little digging:

I'd imagine that it should be possible to design a molecule -- a protein cage, perhaps a (fully unsaturated) terpine -- which isolates the excited state from oxygen quenching.

Adam Cohen at Harvard has been working a bit on this very idea, albeit with fluorescence not phosphorescence --

  • Optical imaging through scattering media via magnetically modulated fluorescence (2010)
    • The two species, pyrene and dimethylaniline are in solution.
    • Dimethylaniline absorbs photons and transfers an electron to pyrene to produce a singlet radical pair.
    • The magnetic field represses conversion of this singlet into a triplet; when two singlet electrons combine, they produce exciplex fluorescence.
  • Addition of an aliphatic-ether 12-O-2 linker improves things significantly --
  • Mapping Nanomagnetic Fields Using a Radical Pair Reaction (2011)
  • Which can be used with a 2p microscope:
  • Two-photon imaging of a magneto-fluorescent indicator for 3D optical magnetometry (2015)
    • Notably, use decay kinetics of the excited state to yield measurements that are insensitive to photobleaching, indicator concentration, or local variations in optical excitation or collection efficiency. (As opposed to ΔF/F\Delta F / F )
    • Used phenanthrene (3 aromatic rings, not 4 in pyrene) as the excited electron acceptor, dimethylaniline again as the photo-electron generator.
    • Clear description:
      • A molecule with a singlet ground state absorbs a photon.
      • The photon drives electron transfer from a donor moiety to an acceptor moiety (either inter or intra molecular).
      • The electrons [ground state and excited state, donor] become sufficiently separated so that their spins do not interact, yet initially they preserve the spin coherence arising from their starting singlet state.
      • Each electron experiences a distinct set of hyperfine couplings to it's surrounding protons (?) leading to a gradual loss of coherence and intersystem crossing (ISC) into a triplet state.
      • An external magnetic field can lock the precession of both electrons to the field axis, partially preserving coherence and supressing ISC.
      • In some chemical systems, the triplet state is non-fluorescence, whereas the singlet pair can recombine and emit a photon.
      • Magnetochemical effects are remarkable because they arise at a magnetic field strengths comparable to hyperfine energy (typically 1-10mT).
        • Compare this to the Zeeman effect, where overt splitting is at 0.1T.
    • phenylanthrene-dimethylaniline was dissolved in dimethylformamide (DMF). The solution was carefully degassed in nitrogen to prevent molecular oxygen quenching.

Yet! Magnetic field effects do exist in solution:

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ref: -2018 tags: Michael Levin youtube talk NIPS 2018 regeneration bioelectricity organism patterning flatworm date: 04-09-2019 18:50 gmt revision:1 [0] [head]

What Bodies Think About: Bioelectric Computation Outside the Nervous System - NeurIPS 2018

  • Short notes from watching the video, mostly interesting factoids: (This is a somewhat more coordinated narrative in the video. Am resisting ending each of these statements with and exclamation point).
  • Human children up to 7-11 years old can regenerate their fingertips.
  • Human embryos, when split in half early, develop into two normal humans; mouse embryos, when squished together, make one normal mouse.
  • Butterflies retain memories from their caterpillar stage, despite their brains liquefying during metamorphosis.
  • Flatworms are immortal, and can both grow and contract, as the environment requires.
    • They can also regenerate a whole body from segments, and know to make one head, tail, gut etc.
  • Single cell organisms, e.g. Lacrymaria, can have complex (and fast!) foraging / hunting plans -- without a brain or anything like it.
  • Axolotl can regenerate many parts of their body (appendages etc), including parts of the nervous system.
  • Frog embryos can self-organize an experimenter jumbled body plan, despite the initial organization having never been experienced in evolution.
  • Salamanders, when their tail is grafted into a foot/leg position, remodel the transplant into a leg and foot.
  • Neurotransmitters are ancient; fungi, who diverged from other forms of life about 1.5 billion years ago, still use the same set of inter-cell transmitters e.g. serotonin, which is why modulatory substances from them have high affinity & a strong effect on humans.
  • Levin, collaborators and other developmental biologists have been using voltage indicators in embryos ... this is not just for neurons.
  • Can make different species head shapes in flatworms by exposing them to ion-channel modulating drugs. This despite the fact that the respective head shapes are from species that have been evolving separately for 150 million years.
  • Indeed, you can reprogram (with light gated ion channels, drugs, etc) to body shapes not seen in nature or not explored by evolution.
    • That said, this was experimental, not by design; Levin himself remarks that the biology that generates these body plans is not known.
  • Flatworms can sore memory in bioelectric networks.
  • Frogs don't normally regenerate their limbs. But, with a drug cocktail targeting bioelectric signaling, they can regenerate semi-functional legs, complete with nerves, muscle, bones, and cartilage. The legs are functional (enough).
  • Manipulations of bioelectric signaling can reverse very serious genetic problems, e.g. deletion of Notch, to the point that tadpoles regain some ability for memory creation & recall.

  • I wonder how so much information can go through a the apparently scalar channel of membrane voltage. It seems you'd get symbol interference, and that many more signals would be required to pattern organs.
  • That said, calcium is used a great many places in the cell for all sorts of signaling tasks, over many different timescales as well, and it doesn't seem to be plagued by interference.
    • First question from the audience was how cells differentiate organismal patterning signals and behavioral signals, e.g. muscle contraction.

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ref: -2017 tags: V1 V4 visual cortex granger causality date: 03-20-2019 06:00 gmt revision:0 [head]

PMID-28739915 Interactions between feedback and lateral connections in the primary visual cortex

  • Liang H1, Gong X1, Chen M2,3, Yan Y2,3, Li W4,3, Gilbert CD5.
  • Extracellular ephys on V1 and V4 neurons in macaque monkeys trained on a fixation and saccade task.
  • Contour task: monkeys had to select the patch of lines, chosen to stimulate the recorded receptive fields, which had a continuous contour in it (again chosen to elicit a response in the recorded V1 / V4 neurons).
    • Variable length of the contour: 1, 3, 5, 7 bars. First part of analysis: only 7-bar trials.
  • Granger causality (GC) in V1 horizontal connectivity decreased significantly in the 0-30Hz band after taking into account V4 activity. Hence, V4 explains some of the causal activity in V1.
    • This result holds both with contour-contour (e.g. cells both tuned to the contours in V1), contour-background, and background-background.
    • Yet there was a greater change in the contour-BG and BG-contour cells when V4 was taken into account (Granger causality is directional, like KL divergence).
      • This result passes the shuffle test, where tria identities were shuffled.
      • True also when LFP is measured.
      • That said .. even though GC is sensitive to temporal features, might be nice to control with a distant area.
      • See supplementary figures (of which there are a lot) for the controls.
  • Summarily: Feedback from V4 strengthens V1 lateral connections.
  • Then they looked at trials with a variable number of contour bars.
  • V4 seems to have a greater GC influence on background cells relative to contour cells.
  • Using conditional GC, lateral interactions in V1 contribute more to contour integration than V4.
  • Greater GC in correct trials than incorrect trials.

  • Note: differences in firing rate can affect estimation of GC. Hence, some advise using thinning of the spike trains to yield parity.
  • Note: refs for horizontal connections in V1 [7-10, 37]

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ref: -2014 tags: gold nanowires intracellular recording korea date: 03-18-2019 23:02 gmt revision:1 [0] [head]

PMID-25112683 Subcellular Neural Probes from Single-Crystal Gold Nanowires

  • Korean authors... Mijeong Kang,† Seungmoon Jung,‡ Huanan Zhang,⊥ Taejoon Kang,∥ Hosuk Kang,† Youngdong Yoo,† Jin-Pyo Hong,# Jae-Pyoung Ahn,⊗ Juhyoun Kwak,† Daejong Jeon,‡* Nicholas A. Kotov,⊥* and Bongsoo Kim†*
  • 100nm single-crystal Au.
  • Able to get SUA despite size.
  • Springy, despite properties of bulk Au.
  • Nanowires fabricated on a sapphire substrae and picked up by a fine shapr W probe, then varnished with nail polish.

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ref: -2011 tags: ttianium micromachining chlorine argon plasma etch oxide nitride penetrating probes Kevin Otto date: 03-18-2019 22:57 gmt revision:1 [0] [head]

PMID-21360044 Robust penetrating microelectrodes for neural interfaces realized by titanium micromachining

  • Patrick T. McCarthyKevin J. OttoMasaru P. Rao
  • Used Cl / Ar plasma to deep etch titanium film, 0.001 / 25um thick. Fine Metals Corp Ashland VA.
  • Discuss various insulation (oxide /nitride) failure modes, lithography issues.

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ref: -2011 tags: Andrew Ng high level unsupervised autoencoders date: 03-15-2019 06:09 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

Building High-level Features Using Large Scale Unsupervised Learning

  • Quoc V. Le, Marc'Aurelio Ranzato, Rajat Monga, Matthieu Devin, Kai Chen, Greg S. Corrado, Jeff Dean, Andrew Y. Ng
  • Input data 10M random 200x200 frames from youtube. Each video contributes only one frame.
  • Used local receptive fields, to reduce the communication requirements. 1000 computers, 16 cores each, 3 days.
  • "Strongly influenced by" Olshausen & Field {1448} -- but this is limited to a shallow architecture.
  • Lee et al 2008 show that stacked RBMs can model simple functions of the cortex.
  • Lee et al 2009 show that convolutonal DBN trained on faces can learn a face detector.
  • Their architecture: sparse deep autoencoder with
    • Local receptive fields: each feature of the autoencoder can connect to only a small region of the lower layer (e.g. non-convolutional)
      • Purely linear layer.
      • More biologically plausible & allows the learning of more invariances other than translational invariances (Le et al 2010).
      • No weight sharing means the network is extra large == 1 billion weights.
        • Still, the human visual cortex is about a million times larger in neurons and synapses.
    • L2 pooling (Hyvarinen et al 2009) which allows the learning of invariant features.
      • E.g. this is the square root of the sum of the squares of its inputs. Square root nonlinearity.
    • Local contrast normalization -- subtractive and divisive (Jarrett et al 2009)
  • Encoding weights W 1W_1 and deconding weights W 2W_2 are adjusted to minimize the reconstruction error, penalized by 0.1 * the sparse pooling layer activation. Latter term encourages the network to find invariances.
  • minimize(W 1,W 2) minimize(W_1, W_2) i=1 m(||W 2W 1 Tx (i)x (i)|| 2 2+λ j=1 kε+H j(W 1 Tx (i)) 2) \sum_{i=1}^m {({ ||W_2 W_1^T x^{(i)} - x^{(i)} ||^2_2 + \lambda \sum_{j=1}^k{ \sqrt{\epsilon + H_j(W_1^T x^{(i)})^2}} })}
    • H jH_j are the weights to the j-th pooling element, λ=0.1\lambda = 0.1 ; m examples; k pooling units.
    • This is also known as reconstruction Topographic Independent Component Analysis.
    • Weights are updated through asynchronous SGD.
    • Minibatch size 100.
    • Note deeper autoencoders don't fare consistently better.

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ref: -2018 tags: biologically inspired deep learning feedback alignment direct difference target propagation date: 03-15-2019 05:51 gmt revision:5 [4] [3] [2] [1] [0] [head]

Assessing the Scalability of Biologically-Motivated Deep Learning Algorithms and Architectures

  • Sergey Bartunov, Adam Santoro, Blake A. Richards, Luke Marris, Geoffrey E. Hinton, Timothy Lillicrap
  • As is known, many algorithms work well on MNIST, but fail on more complicated tasks, like CIFAR and ImageNet.
  • In their experiments, backprop still fares better than any of the biologically inspired / biologically plausible learning rules. This includes:
    • Feedback alignment {1432} {1423}
    • Vanilla target propagation
      • Problem: with convergent networks, layer inverses (top-down) will map all items of the same class to one target vector in each layer, which is very limiting.
      • Hence this algorithm was not directly investigated.
    • Difference target propagation (2015)
      • Uses the per-layer target as h^ l=g(h^ l+1;λ l+1)+[h lg(h l+1;λ l+1)]\hat{h}_l = g(\hat{h}_{l+1}; \lambda_{l+1}) + [h_l - g(h_{l+1};\lambda_{l+1})]
      • Or: h^ l=h l+g(h^ l+1;λ l+1)g(h l+1;λ l+1)\hat{h}_l = h_l + g(\hat{h}_{l+1}; \lambda_{l+1}) - g(h_{l+1};\lambda_{l+1}) where λ l\lambda_{l} are the parameters for the inverse model; g()g() is the sum and nonlinearity.
      • That is, the target is modified ala delta rule by the difference between inverse-propagated higher layer target and inverse-propagated higher level activity.
        • Why? h lh_{l} should approach h^ l\hat{h}_{l} as h l+1h_{l+1} approaches h^ l+1\hat{h}_{l+1} .
        • Otherwise, the parameters in lower layers continue to be updated even when low loss is reached in the upper layers. (from original paper).
      • The last to penultimate layer weights is trained via backprop to prevent template impoverishment as noted above.
    • Simplified difference target propagation
      • The substitute a biologically plausible learning rule for the penultimate layer,
      • h^ L1=h L1+g(h^ L;λ L)g(h L;λ L)\hat{h}_{L-1} = h_{L-1} + g(\hat{h}_L;\lambda_L) - g(h_L;\lambda_L) where there are LL layers.
      • It's the same rule as the other layers.
      • Hence subject to impoverishment problem with low-entropy labels.
    • Auxiliary output simplified difference target propagation
      • Add a vector zz to the last layer activation, which carries information about the input vector.
      • zz is just a set of random features from the activation h L1h_{L-1} .
  • Used both fully connected and locally-connected (e.g. convolution without weight sharing) MLP.
  • It's not so great:
  • Target propagation seems like a weak learner, worse than feedback alignment; not only is the feedback limited, but it does not take advantage of the statistics of the input.
    • Hence, some of these schemes may work better when combined with unsupervised learning rules.
    • Still, in the original paper they use difference-target propagation with autoencoders, and get reasonable stroke features..
  • Their general result that networks and learning rules need to be tested on more difficult tasks rings true, and might well be the main point of this otherwise meh paper.

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ref: Schmidt-1978.09 tags: Schmidt BMI original operant conditioning cortex HOT pyramidal information antidromic date: 03-12-2019 23:35 gmt revision:11 [10] [9] [8] [7] [6] [5] [head]

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

  • Hand-arm area of M1, 11 or 12 chronic recording electrodes, 3 monkeys.
    • But, they only used one unit at a time in the conditioning task.
  • Observed conditioning in 77% of single units and 65% of combined units (multiunits?).
  • Trained to move a handle to a position indicated by 8 annular cursor lights.
    • Cursor was updated at 50hz -- this was just a series of lights! talk about simple feedback...
    • Investigated different smoothing: too fast, FR does not stay in target; too slow, cursor acquires target too slowly.
      • My gamma function is very similar to their lowpass filter used for smoothing the firing rates.
    • 4 or 8 target random tracking task
    • Time-out of 8 seconds
    • Run of 40 trials
      • The conditioning reached a significant level of performance after 2.2 runs of 40 trials (in well-trained monkeys); typically, they did 18 runs/day (720 trials)
  • Recordings:
    • Scalar mapping of unit firing rate to cursor position.
    • Filtered 600-6kHz
    • Each accepted spike triggered a generator that produced a pulse of of constant amplitude and width -> this was fed into a lowpass filter (1.5 to 2.5 & 3.5Hz cutoff), and a gain stage, then a ADC, then (presumably) the PDP.
      • can determine if these units were in the pyramidal tract by measuring antidromic delay.
    • recorded one neuron for 108 days!!
      • Neuronal activity is still being recorded from one monkey 24 months after chronic implantation of the microelectrodes.
    • Average period in which conditioning was attempted was 3.12 days.
  • Successful conditioning was always associated with specific repeatable limb movements
    • "However, what appears to be conditioned in these experiments is a movement, and the neuron under study is correlated with that movement." YES.
    • The monkeys clearly learned to make (increasingly refined) movement to modulate the firing activity of the recorded units.
    • The monkey learned to turn off certain units with specific limb positions; the monkey used exaggerated movements for these purposes.
      • e.g. finger and shoulder movements, isometric contraction in one case.
  • Trained some monkeys or > 15 months; animals got better at the task over time.
  • PDP-12 computer.
  • Information measure: 0 bits for missed targets, 2 for a 4 target task, 3 for 8 target task; information rate = total number of bits / time to acquire targets.
    • 3.85 bits/sec peak with 4 targets, 500ms hold time
    • With this, monkeys were able to exert fine control of firing rate.
    • Damn! compare to Paninski! [1]
  • 4.29 bits/sec when the same task was performed with a manipulandum & wrist movement
  • they were able to condition 77% of individual neurons and 65% of combined units.
  • Implanted a pyramidal tract electrode in one monkey; both cells recorded at that time were pyramidal tract neurons, antidromic latencies of 1.2 - 1.3ms.
    • Failures had no relation to over movements of the monkey.
  • Fetz and Baker [2,3,4,5] found that 65% of precentral neurons could be conditioned for increased or decreased firing rates.
    • and it only took 6.5 minutes, on average, for the units to change firing rates!
  • Summarized in [1].

____References____

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ref: -0 tags: sparse coding reference list olshausen field date: 03-11-2019 21:59 gmt revision:3 [2] [1] [0] [head]

This was compiled from searching papers which referenced Olhausen and Field 1996 PMID-8637596 Emergence of simple-cell receptive field properties by learning a sparse code for natural images.

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ref: -2015 tags: conjugate light electron tomography mouse visual cortex fluorescent label UNC cryoembedding date: 03-11-2019 19:37 gmt revision:1 [0] [head]

PMID-25855189 Mapping Synapses by Conjugate Light-Electron Array Tomography

  • Use aligned interleaved immunofluorescence imaging follwed by array EM (FESEM). 70nm thick sections.
  • Of IHC, tissue must be dehydrated & embedded in a resin.
  • However, the dehydration disrupts cell membranes and ultrastructural details viewed via EM ...
  • Hence, EM microscopy uses osmium tetroxide to cross-link the lipids.
  • ... Yet that also disrupt / refolds the poteins, making IHC fail.
  • Solution is to dehydrate & embed at cryo temp, -70C, where the lipids do not dissolve. They used Lowicryl HM-20.
  • We show that cryoembedding provides markedly improved ultrastructure while still permitting multiplexed immunohistochemistry.

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ref: -2004 tags: Olshausen sparse coding review date: 03-08-2019 07:02 gmt revision:0 [head]

PMID-15321069 Sparse coding of sensory inputs

  • Classic review, Olshausen and Field. 15 years old now!
  • Note the sparsity here is in neuronal activation, not synaptic activity (though one should follow the other).
  • References Lewicki's auditory studies, Efficient coding of natural sounds 2002; properties of early auditory neurons are well suited for producing a sparse independent code.
    • Studies have found near binary encoding of stimuli in rat auditory cortex -- e.g. one spike per noise.
  • Suggests that overcomplete representations (e.g. where there are more 'second layer' neurons than inputs or pixels) are useful for flattening manifolds in the input space, making feature extraction easier.
    • But then you have an under-determined problem, where presumably sparsity metrics step in to restrict the actual coding space. Authors mention that this could lead to degeneracy.
    • Example is the early visual cortex, where axons to higher layers exceed those from the LGN by a factor of 25. Which, they say, may be a compromise between over-representation and degeneracy.
  • Sparse coding is a necessity from an energy standpoint -- only one in 50 neurons can be active at any given time.
  • Sparsity increases when classical receptive field stimuli in V1 is expanded with a real-world-statistics surround. (Gallant 2002).

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ref: -2017 tags: vicarious dileep george captcha message passing inference heuristic network date: 03-06-2019 04:31 gmt revision:2 [1] [0] [head]

PMID-29074582 A generative vision model that trains with high data efficiency and breaks text-based CAPTCHAs

  • Vicarious supplementary materials on their RCN (recursive cortical network).
  • Factor scene into shape and appearance, which CNN or DCNN do not do -- they conflate (ish? what about the style networks?)
    • They call this the coloring book approach -- extract shape then attach appearance.
  • Hierarchy of feature layers F frcF_{f r c} (binary) and pooling layer H frcH_{f r c} (multinomial), where f is feature, r is row, c is column (e.g. over image space).
  • Each layer is exclusively conditional on the layer above it, and all features in a layer are conditionally independent given the layer above.
  • Pool variables H frcH_{f r c} is multinomial, and each value associated with a feature, plus one off feature.
    • These features form a ‘pool’, which can/does have translation invariance.
  • If any of the pool variables are set to enable FF , then that feature is set (or-operation). Many pools can contain a given feature.
  • One can think of members of a pool as different alternatives of similar features.
  • Pools can be connected laterally, so each is dependent on the activity of its neighbors. This can be used to enforce edge continuity.
  • Each bottom-level feature corresponds to an edge, which defines ‘in’ and ‘out’ to define shape, YY .
  • These variables YY are also interconnected, and form a conditional random field, a ‘Potts model’. YY is generated by gibbs sampling given the F-H hierarchy above it.
  • Below Y, the per-pixel model X specifies texture with some conditional radial dependence.
  • The model amounts to a probabalistic model for which exact inference is impossible -- hence you must do approximate, where a bottom up pass estimates the category (with lateral connections turned off), and a top down estimates the object mask. Multiple passes can be done for multiple objects.
  • Model has a hard time moving from rgb pixels to edge ‘in’ and ‘out’; they use edge detection pre-processing stage, e.g. Gabor filter.
  • Training follows a very intuitive, hierarchical feature building heuristic, where if some object or collection of lower level features is not present, it’s added to the feature-pool tree.
    • This includes some winner-take-all heuristic for sparsification.
    • Also greedily learn some sort of feature ‘’dictionary’’ from individual unlabeled images.
  • Lateral connections are learned similarly, with a quasi-hebbian heuristic.
  • Neuroscience inspiration: see refs 9, 98 for message-passing based Bayesian inference.

  • Overall, a very heuristic, detail-centric, iteratively generated model and set of algorithms. You get the sense that this was really the work of Dileep George or only a few people; that it was generated by successively patching and improving the model/algo to make up for observed failures and problems.
    • As such, it offers little long-term vision for what is possible, or how perception and cognition occurs.
    • Instead, proof is shown that, well, engineering works, and the space of possible solutions -- including relatively simple elements like dictionaries and WTA -- is large and fecund.
      • Unclear how this will scale to even more complex real-world problems, where one would desire a solution that does not have to have each level carefully engineered.
      • Modern DCNN, at least, do not seem to have this property -- the structure is learned from the (alas, labeled) data.
  • This extends to the fact that yes, their purpose-built system achieves state of the art performance on the designated CAPATCHA tasks.
  • Check: B. M. Lake, R. Salakhutdinov, J. B. Tenenbaum, Human-level concept learning through probabilistic program induction. Science 350, 1332–1338 (2015). doi:10.1126/science.aab3050 Medline

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ref: -2019 tags: three photon imaging visual cortex THG chirp NOPA mice GCaMP6 MIT date: 03-01-2019 18:46 gmt revision:2 [1] [0] [head]

PMID-30635577 Functional imaging of visual cortical layers and subplate in awake mice with optimized three photon microscopy

  • Murat Yildirim, Hiroki Sugihara, Peter T.C. So & Mriganka Sur'
  • Used a fs Ti:Saphirre 16W pump into a non-colinear optical parametric amplifier (both from Spectra-Physics) to generate the 1300nm light.
  • Used pulse compensation to get the pulse width at the output of the objective to 40 fS.
    • Three-photon cross section is inverse quadratic in pulse width:
    • NP 3δ(τR) 2(NA 22hcλ) 3 N \sim \frac{P^3 \delta}{(\tau R)^2} (\frac{NA^2}{2hc\lambda})^3
    • P is power, δ\delta is 3p cross-section, τ\tau is pulse width, R repetition rate, NA is the numerical aperture (sixth power of NA!!!), h c and λ\lambda Planks constant, speed of light, and wavelength respectively.
  • Optimized excitation per depth by monitoring damage levels. varied from 0.5nJ to 5 nJ.
  • Imaged up to 1.5mm deep! All the way to the white matter / subplate.
  • Allegedly used a custom scan and tube lens to minimize aberrations in the excitation path (hence improve 3p excitation)
  • Layer 5 neurons are more broadly tuned for orientation than other layers. But the data is not dramatic.
  • Used straightforward metrics for tuning, using a positive and negative bump gaussian fit, then vector averaging to get global orientation selectivity.
  • Interesting that the variance between layers seems higher than between mice.

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ref: -2017 tags: attention transformer language model youtube google tech talk date: 02-26-2019 20:28 gmt revision:3 [2] [1] [0] [head]

Attention is all you need

  • Ashish Vaswani, Noam Shazeer, Niki Parmar, Jakob Uszkoreit, Llion Jones, Aidan N. Gomez, Lukasz Kaiser, Illia Polosukhin
  • Attention is all you need neural network models
  • Good summary, along with: The Illustrated Transformer (please refer to this!)
  • Łukasz Kaiser mentions a few times how fragile the network is -- how easy it is to make something that doesn't train at all, or how many tricks by google experts were needed to make things work properly. it might be bravado or bluffing, but this is arguably not the way that biology fails.
  • Encoding:
  • Input is words encoded as 512-length vectors.
  • Vectors are transformed into length 64 vectors: query, key and value via differentiable weight matrices.
  • Attention is computed as the dot-product of the query (current input word) with the keys (values of the other words).
    • This value is scaled and passed through a softmax function to result in one attentional signal scaling the value.
  • Multiple heads' output are concatenated together, and this output is passed through a final weight matrix to produce a final value for the next layer.
    • So, attention in this respect looks like a conditional gain field.
  • 'Final value' above is then passed through a single layer feedforward net, with resnet style jump.
  • Decoding:
  • Use the attentional key value from the encoder to determine the first word through the output encoding (?) Not clear.
  • Subsequent causal decodes depend on the already 'spoken' words, plus the key-values from the encoder.
  • Output is a one-hot softmax layer from a feedforward layer; the sum total is differentiable from input to output using cross-entropy loss or KL divergence.

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ref: -2015 tags: CWEETS amplified Fourier imaging raman amplification date: 02-19-2019 06:46 gmt revision:1 [0] [head]

Amplified dispersive Fourier-Transform Imaging for Ultrafast Displacement sensing and Barcode Reading

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ref: -2011 tags: HiLo speckle imaging confocal boston university optical sectioning date: 02-19-2019 06:18 gmt revision:2 [1] [0] [head]

PMID-21280920 Optically sectioned in vivo imaging with speckle illumination HiLo microscopy

  • Ah, brilliant! Illuminate a sample with a speckle pattern from a laser, and use this to optically section the data -- the contrast of the speckle pattern shows how in focus the sample is.
    • Hanece, the contrast indicates the in-focus vs out-of-focus ratio in a region.
  • The speckle statistics are invariant even in a scattering media, as scattering only further randomizes an already random laser phase front. (Within some limits.)
  • HiLo microscopy involves illuminating with a speckle pattern, then illuminating with standard uniform illumination, resulting in a diffraction-limited optically sectioned image. PMID-18709098
  • Algorithm is :
    • Take the speckle image and subtract the uniform image δI\delta I
    • Bandpass δI\delta I
    • Measure the standard deviation of the δI\delta I to get a weighting function C δs 2C^2_{\delta s}
    • Debias this estimate based on sensor..
    • Generate low-passed image from the weighted uniform image, LP[C δsI u] LP[C_{\delta s} I_u] , and high-pass from the difference HP=1LPHP = 1 - LP
    • Resultand image is a weighted sum of highpassed and lowpassed images.
  • Looks about as good as confocal.
  • Cited by...

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ref: -0 tags: Airy light sheet microscopy attenuation compensation LSM imaging date: 02-19-2019 04:51 gmt revision:1 [0] [head]

Light-sheet microscopy with attenuation-compensated propagation-invariant beams

  • Ah ... beautiful illustration of the airy light sheet concept.
  • In practice, used a LCOS SLM to generate the beam (as .. phase matters!) plus an AOM to scan the beam.
    • Microscope can operate either in SPIM (single plane imaging microscope) or DSLM (digital scanning light sheet microscope),
  • Improves signal-to-background ratio (SBR) and contrast-to-noise ratio (CNR) (not sure why they don't use SNR..?)

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ref: -0 tags: variational free energy inference learning bayes curiosity insight Karl Friston date: 02-15-2019 02:09 gmt revision:1 [0] [head]

PMID-28777724 Active inference, curiosity and insight. Karl J. Friston, Marco Lin, Christopher D. Frith, Giovanni Pezzulo,

  • This has been my intuition for a while; you can learn abstract rules via active probing of the environment. This paper supports such intuitions with extensive scholarship.
  • “The basic theme of this article is that one can cast learning, inference, and decision making as processes that resolve uncertanty about the world.
    • References Schmidhuber 1991
  • “A learner should choose a policy that also maximizes the learner’s predictive power. This makes the world both interesting and exploitable.” (Still and Precup 2012)
  • “Our approach rests on the free energy principle, which asserts that any sentient creature must minimize the entropy of its sensory exchanges with the world.” Ok, that might be generalizing things too far..
  • Levels of uncertainty:
    • Perceptual inference, the causes of sensory outcomes under a particular policy
    • Uncertainty about policies or about future states of the world, outcomes, and the probabilistic contingencies that bind them.
  • For the last element (probabilistic contingencies between the world and outcomes), they employ Bayesian model selection / Bayesian model reduction
    • Can occur not only on the data, but exclusively on the initial model itself.
    • “We use simulations of abstract rule learning to show that context-sensitive contingiencies, which are manifest in a high-dimensional space of latent or hidden states, can be learned with straightforward variational principles (ie. minimization of free energy).
  • Assume that initial states and state transitions are known.
  • Perception or inference about hidden states (i.e. state estimation) corresponds to inverting a generative model gievn a sequence of outcomes, while learning involves updating the parameters of the model.
  • The actual task is quite simple: central fixation leads to a color cue. The cue + peripheral color determines either which way to saccade.
  • Gestalt: Good intuitions, but I’m left with the impression that the authors overexplain and / or make the description more complicated that it need be.
    • The actual number of parameters to to be inferred is rather small -- 3 states in 4 (?) dimensions, and these parameters are not hard to learn by minimizing the variational free energy:
    • F=D[Q(x)||P(x)]E q[ln(P(o t|x)]F = D[Q(x)||P(x)] - E_q[ln(P(o_t|x)] where D is the Kullback-Leibler divergence.
      • Mean field approximation: Q(x)Q(x) is fully factored (not here). many more notes

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ref: -2014 tags: Lillicrap Random feedback alignment weights synaptic learning backprop MNIST date: 02-14-2019 01:02 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-27824044 Random synaptic feedback weights support error backpropagation for deep learning.

  • "Here we present a surprisingly simple algorithm for deep learning, which assigns blame by multiplying error signals by a random synaptic weights.
  • Backprop multiplies error signals e by the weight matrix W T W^T , the transpose of the forward synaptic weights.
  • But the feedback weights do not need to be exactly W T W^T ; any matrix B will suffice, so long as on average:
  • e TWBe>0 e^T W B e > 0
    • Meaning that the teaching signal Be B e lies within 90deg of the signal used by backprop, W Te W^T e
  • Feedback alignment actually seems to work better than backprop in some cases. This relies on starting the weights very small (can't be zero -- no output)

Our proof says that weights W0 and W
evolve to equilibrium manifolds, but simulations (Fig. 4) and analytic results (Supple-
mentary Proof 2) hint at something more specific: that when the weights begin near
0, feedback alignment encourages W to act like a local pseudoinverse of B around
the error manifold. This fact is important because if B were exactly W + (the Moore-
Penrose pseudoinverse of W ), then the network would be performing Gauss-Newton
optimization (Supplementary Proof 3). We call this update rule for the hidden units
pseudobackprop and denote it by ∆hPBP = W + e. Experiments with the linear net-
work show that the angle, ∆hFA ]∆hPBP quickly becomes smaller than ∆hFA ]∆hBP
(Fig. 4b, c; see Methods). In other words feedback alignment, despite its simplicity,
displays elements of second-order learning.

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ref: -0 tags: diffraction terahertz 3d print ucla deep learning optical neural networks date: 02-13-2019 23:16 gmt revision:1 [0] [head]

All-optical machine learning using diffractive deep neural networks

  • Pretty clever: use 3D printed plastic as diffractive media in a 0.4 THz all-optical all-interference (some attenuation) linear convolutional multi-layer 'neural network'.
  • In the arxive publication there are few details on how they calculated or optimized given diffractive layers.
  • Absence of nonlinearity will limit things greatly.
  • Actual observed performance (where thy had to print out the handwritten digits) rather poor, ~ 60%.

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ref: -2017 tags: calcium imaging seeded iterative demixing light field microscopy mouse cortex hippocampus date: 02-13-2019 22:44 gmt revision:1 [0] [head]

PMID-28650477 Video rate volumetric Ca2+ imaging across cortex using seeded iterative demixing (SID) microscopy

  • Tobias Nöbauer, Oliver Skocek, Alejandro J Pernía-Andrade, Lukas Weilguny, Francisca Martínez Traub, Maxim I Molodtsov & Alipasha Vaziri
  • Cell-scale imaging at video rates of hundreds of GCaMP6 labeled neurons with light-field imaging followed by computationally-efficient deconvolution and iterative demixing based on non-negative factorization in space and time.
  • Utilized a hybrid light-field and 2p microscope, but didn't use the latter to inform the SID algorithm.
  • Algorithm:
    • Remove motion artifacts
    • Time iteration:
      • Compute the standard deviation versus time (subtract mean over time, measure standard deviance)
      • Deconvolve standard deviation image using Richardson-Lucy algo, with non-negativity, sparsity constraints, and a simulated PSF.
      • Yields hotspots of activity, putative neurons.
      • These neuron lcoations are convolved with the PSF, thereby estimating its ballistic image on the LFM.
      • This is converted to a binary mask of pixels which contribute information to the activity of a given neuron, a 'footprint'
        • Form a matrix of these footprints, p * n, S 0S_0 (p pixels, n neurons)
      • Also get the corresponding image data YY , p * t, (t time)
      • Solve: minimize over T ||YST|| 2|| Y - ST||_2 subject to T0T \geq 0
        • That is, find a non-negative matrix of temporal components TT which predicts data YY from masks SS .
    • Space iteration:
      • Start with the masks again, SS , find all sets O kO^k of spatially overlapping components s is_i (e.g. where footprints overlap)
      • Extract the corresponding data columns t it_i of T (from temporal step above) from O kO^k to yield T kT^k . Each column corresponds to temporal data corresponding to the spatial overlap sets. (additively?)
      • Also get the data matrix Y kY^k that is image data in the overlapping regions in the same way.
      • Minimize over S kS^k ||Y kS kT k|| 2|| Y^k - S^k T^k||_2
      • Subject to S k>=0S^k >= 0
        • That is, solve over the footprints S kS^k to best predict the data from the corresponding temporal components T kT^k .
        • They also impose spatial constraints on this non-negative least squares problem (not explained).
    • This process repeats.
    • allegedly 1000x better than existing deconvolution / blind source segmentation algorithms, such as those used in CaImAn

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ref: -0 tags: superresolution imaging scanning lens nanoscale date: 02-04-2019 20:34 gmt revision:1 [0] [head]

PMID-27934860 Scanning superlens microscopy for non-invasive large field-of-view visible light nanoscale imaging

  • Recently, the diffraction barrier has been surpassed by simply introducing dielectrics with a micro-scale spherical configuration when using conventional optical microscopes by transforming evanescent waves into propagating waves. 18,19,20,21,22,23,24,25,26,27,28,29,30
  • The resolution of this superlens-based microscopy has been decreased to ∼50 nm (ref. 26) from an initial resolution of ∼200 nm (ref. 21).
  • This method can be further enhanced to ∼25 nm when coupled with a scanning laser confocal microscope 31.
  • It has achieved fast development in biological applications, as the sub-diffraction-limited resolution of high-index liquid-immersed microspheres has now been demonstrated23,32, enabling its application in the aqueous environment required to maintain biological activity.
  • Microlens is a 57 um diameter BaTiO3 microsphere, resolution of lambda / 6.3 under partial and inclined illumination
  • Microshpere is in contact with the surface during imaging, by gluing it to the cantilever tip of an AFM.
  • Get an image with the microsphere-lens, which improves imaging performance by ~ 200x. (with a loss in quality, naturally).

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ref: -0 tags: Kato fear conditioning GABA auditory cortex mice optogenetics SOM PV date: 02-04-2019 19:09 gmt revision:0 [head]

PMID-29375323 Fear learning regulates cortical sensory representation by suppressing habituation

  • Trained mice on CS+ and CS --> lick task.
    • CS+ = auditory tone followed by tailshock
    • CS- = auditory tone (both FM modulated, separated by 0.5 - 1.0 octave).
    • US = licking.
  • VGAT2-ChR2 or PV-ChR2
  • GABA-ergic silencing of auditory cortex through blue light illumination abolished behavior difference following CS+ and CS-.
  • Used intrinsic imaging to locate A1 cortex, then AAV - GCaMP6 imaging to lcoated pyramidal cells.
  • In contrast to reports of enhanced tone responses following simple fear conditioning (Quirk et al., 1997; Weinberger, 2004, 2015), discriminative learning under our conditions caused no change in the average fraction of pyramidal cells responsive to the CS+ tone.
    • Seemed to be an increase in suppression, and reduced cortical responses, which is consistent with habituation.
  • Whereas -- and this is by no means surprising -- cortical responses to CS+ were sustained at end of tone following fear conditioning.
  • ----
  • Then examined this effect relative to the two populations of interneurons, using PV-cre and SOM-cre mice.
    • In PV cells, fear conditioning resulted in a decreased fraction of cells responsive, and a decreased magnitude of responses.
    • In SOM cells, CS- responses were enhanced, while CS+ were less enhanced (the main text seems like an exaggeration c.f. figure 6E)
  • This is possibly the more interesting result of the paper, but even then the result is not super strong.

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ref: -0 tags: lillicrap segregated dendrites deep learning backprop date: 01-31-2019 19:24 gmt revision:2 [1] [0] [head]

PMID-29205151 Towards deep learning with segregated dendrites https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5716677/

  • Much emphasis on the problem of credit assignment in biological neural networks.
    • That is: given complex behavior, how do upstream neurons change to improve the task of downstream neurons?
    • Or: given downstream neurons, how do upstream neurons receive ‘credit’ for informing behavior?
      • I find this a very limiting framework, and is one of my chief beefs with the work.
      • Spatiotemporal Bayesian structure seems like a much better axis (axes) to cast function against.
      • Or, it could be segregation into ‘signal’ and ‘error’ or ‘figure/ground’ based on hierarchical spatio-temporal statistical properties that matters ...
      • ... with proper integration of non-stochastic spike timing + neoSTDP.
        • This still requires some solution of the credit-assignment problem, i know i know.
  • Outline a spiking neuron model with zero one or two hidden layers, and a segregated apical (feedback) and basal (feedforward) dendrites, as per a layer 5 pyramidal neuron.
  • The apical dendrites have plateau potentials, which are stimulated through (random) feedback weights from the output neurons.
  • Output neurons are forced to one-hot activation at maximum firing rate during training.
    • In order to assign credit, feedforward information must be integrated separately from any feedback signals used to calculate error for synaptic updates (the error is indicated here with δ). (B) Illustration of the segregated dendrites proposal. Rather than using a separate pathway to calculate error based on feedback, segregated dendritic compartments could receive feedback and calculate the error signals locally.
  • Uses the MNIST database, naturally.
  • Poisson spiking input neurons, 784, again natch.
  • Derive local loss function learning rules to make the plateau potential (from the feedback weights) match the feedforward potential
    • This encourages the hidden layer -> output layer to approximate the inverse of the random feedback weight network -- which it does! (At least, the jacobians are inverses of each other).
    • The matching is performed in two phases -- feedforward and feedback. This itself is not biologically implausible, just unlikely.
  • Achieved moderate performance on MNIST, ~ 4%, which improved with 2 hidden layers.
  • Very good, interesting scholarship on the relevant latest findings ‘’in vivo’’.
  • While the model seems workable though ad-hoc or just-so, the scholarship points to something better: use of multiple neuron subtypes to accomplish different elements (variables) in the random-feedback credit assignment algorithm.
    • These small models can be tuned to do this somewhat simple task through enough fiddling & manual (e.g. in the algorithmic space, not weight space) backpropagation of errors.
  • They suggest that the early phases of learning may entail learning the feedback weights -- fascinating.
  • ‘’Things are definitely moving forward’’.

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ref: -0 tags: cutting plane manifold learning classification date: 10-31-2018 23:49 gmt revision:0 [head]

Learning data manifolds with a Cutting Plane method

  • Looks approximately like SVM: perform binary classification on a high-dimensional manifold (or sets of manifolds in this case).
  • The general idea behind Mcp_simple is to start with a finite number of training examples, find the maximum margin solution for that training set, augment the draining set by finiding a poing on the manifolds that violates the constraints, iterating the process until a tolerance criteria is met.
  • The more complicated cutting plane SVM uses slack variables to allow solution where classification is not linearly separable.
    • Propose using one slack variable per manifold, plus a manifold center, which strictly obeys the margin (classification) constraint.
  • Much effort put to proving the convergence properties of these algorithms; admittedly I couldn't be bothered to read...

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ref: -0 tags: hahnloser zebrafinch LMAN HVC song learning internal model date: 10-12-2018 00:33 gmt revision:1 [0] [head]

PMID-24711417 Evidence for a causal inverse model in an avian cortico-basal ganglia circuit

  • Recorded an stimulated the LMAN (upstream, modulatory) region of the zebrafinch song-production & learning pathway.
  • Found evidence, albeit weak, for a mirror arrangement or 'causal inverse' there: neurons fire bursts prior syllable production with some motor delay, ~30ms, and also fire single spikes with a delay ~10 ms to the same syllables.
    • This leads to an overall 'mirroring offset' of about 40 ms, which is sufficiently supported by the data.
    • The mirroring offset is quantified by looking at the cross-covariance of audio-synchronized motor and sensory firing rates.
  • Causal inverse: a sensory target input generates a motor activity pattern required to cause, or generate that same sensory target.
    • Similar to the idea of temporal inversion via memory.
  • Data is interesting, but not super strong; per the discussion, the authors were going for a much broader theory:
    • Normal Hebbian learning says that if a presynaptic neuron fires before a postsynaptic neuron, then the synapse is potentiated.
    • However, there is another side of the coin: if the presynaptic neuron fires after the postsynaptic neuron, the synapse can be similarly strengthened, permitting the learning of inverse models.
      • "This order allows sensory feedback arriving at motor neurons to be associated with past postsynaptic patterns of motor activity that could have caused this sensory feedback. " So: stimulate the sensory neuron (here hypothetically in LMAN) to get motor output; motor output is indexed in the sensory space.
      • In mammals, a similar rule has been found to describe synaptic connections from the cortex to the basal ganglia [37].
      • ... or, based on anatomy, a causal inverse could be connected to a dopaminergic VTA, thereby linking with reinforcement learning theories.
      • Simple reinforcement learning strategies can be enhanced with inverse models as a means to solve the structural credit assignment problem [49].
  • Need to review literature here, see how well these theories of cortical-> BG synapse match the data.

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ref: -0 tags: deeplabcut markerless tracking DCN transfer learning date: 10-03-2018 23:56 gmt revision:0 [head]

Markerless tracking of user-defined features with deep learning

  • Human - level tracking with as few as 200 labeled frames.
  • No dynamics - could be even better with a Kalman filter.
  • Uses a Google-trained DCN, 50 or 101 layers deep.
    • Network has a distinct read-out layer per feature to localize the probability of a body part to a pixel location.
  • Uses the DeeperCut network architecture / algorithm for pose estimation.
  • These deep features were trained on ImageNet
  • Trained on examples with both only the readout layers (rest fixed per ResNet), as well as end-to-end; latter performs better, unsurprising.

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ref: -0 tags: NMDA spike hebbian learning states pyramidal cell dendrites date: 10-03-2018 01:15 gmt revision:0 [head]

PMID-20544831 The decade of the dendritic NMDA spike.

  • NMDA spikes occur in the finer basal, oblique, and tuft dendrites.
  • Typically 40-50 mV, up to 100's of ms in duration.
  • Look similar to cortical up-down states.
  • Permit / form the substrate for spatially and temporally local computation on the dendrites that can enhance the representational or computational repertoire of individual neurons.

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ref: -0 tags: kernel regression structure discovery fitting gaussian process date: 09-24-2018 22:09 gmt revision:1 [0] [head]

Structure discovery in Nonparametric Regression through Compositional Kernel Search

  • Use Gaussian process kernels (squared exponential, periodic, linear, and ratio-quadratic)
  • to model a kernel function, k(x,x)k(x,x') which specifies how similar or correlated outputs yy and yy' are expected to be at two points $$x$ and xx' .
    • By defining the measure of similarity between inputs, the kernel determines the pattern of inductive generalization.
    • This is different than modeling the mapping y=f(x)y = f(x) .
    • It's something more like y=N(m(x)+k(x,x))y' = N(m(x') + k(x,x')) -- check the appendix.
    • See also: http://rsta.royalsocietypublishing.org/content/371/1984/20110550
  • Gaussian process models use a kernel to define the covariance between any two function values: Cov(y,y)=k(x,x)Cov(y,y') = k(x,x') .
  • This kernel family is closed under addition and multiplication, and provides an interpretable structure.
  • Search for kernel structure greedily & compositionally,
    • then optimize parameters with conjugate gradients with restarts.
    • This seems straightforwardly intuitive...
  • Kernels are scored with the BIC.
  • C.f. {842} -- "Because we learn expressions describing the covariance structure rather than the functions themselves, we are able to capture structure which does not have a simple parametric form."
  • All their figure examples are 1-D time-series, which is kinda boring, but makes sense for creating figures.
    • Tested on multidimensional (d=4) synthetic data too.
    • Not sure how they back out modeling the covariance into actual predictions -- just draw (integrate) from the distribution?

{842}
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ref: work-0 tags: distilling free-form natural laws from experimental data Schmidt Cornell automatic programming genetic algorithms date: 09-14-2018 01:34 gmt revision:5 [4] [3] [2] [1] [0] [head]

Distilling free-form natural laws from experimental data

  • There critical step was to use partial derivatives to evaluate the search for invariants. Even yet, with a 4D data set the search for natural laws took ~ 30 hours.
    • Then again, how long did it take humans to figure out these invariants? (Went about it in a decidedly different way..)
    • Further, how long did it take for biology to discover similar invariants?
      • They claim elsewhere that the same algorithm has been applied to biological data - a metabolic pathway - with some success.
      • Of course evolution had to explore a much larger space - proteins and reculatory pathways, not simpler mathematical expressions / linkages.

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ref: -2018 tags: machine learning manifold deep neural net geometry regularization date: 08-29-2018 14:30 gmt revision:0 [head]

LDMNet: Low dimensional manifold regularized neural nets.

  • Synopsis of the math:
    • Fit a manifold formed from the concatenated input ‘’and’’ output variables, and use this set the loss of (hence, train) a deep convolutional neural network.
      • Manifold is fit via point integral method.
      • This requires both SGD and variational steps -- alternate between fitting the parameters, and fitting the manifold.
      • Uses a standard deep neural network.
    • Measure the dimensionality of this manifold to regularize the network. Using a 'elegant trick', whatever that means.
  • Still yet he results, in terms of error, seem not very significantly better than previous work (compared to weight decay, which is weak sauce, and dropout)
    • That said, the results in terms of feature projection, figures 1 and 2, ‘’do’’ look clearly better.
    • Of course, they apply the regularizer to same image recognition / classification problems (MNIST), and this might well be better adapted to something else.
  • Not completely thorough analysis, perhaps due to space and deadlines.

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

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

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

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

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

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

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

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

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

____References____

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

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

PMID-23451719 Synthetic Nanoelectronic Probes for Biological Cells and Tissue

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

{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.

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

Method of electropolishing tungsten wire US 3287238 A

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

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

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

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

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

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

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

____References____

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

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

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

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

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

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

{1382}
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ref: -0 tags: iridium oxide nanotube intracellular recording electroplate MEA date: 02-22-2017 22:41 gmt revision:0 [head]

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

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

{1380}
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ref: -0 tags: myoelectric EMG recording TMR prosthetics date: 02-13-2017 20:43 gmt revision:0 [head]

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

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

{1378}
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ref: -0 tags: carbon fiber thread spinning Pasquali Kemere nanotube stimulation date: 02-09-2017 01:09 gmt revision:0 [head]

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

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

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

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

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

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

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

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

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

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

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

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

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

Tensile and Flextural Prperties of single carbon fibers

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

____References____

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

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

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

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

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

China 'social credit': Beijing sets up huge system

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

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

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


Other comments:

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

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

Physical Metallurgy of Refactory Metals and Alloys

Properties of tungsten-rhenium alloys

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

PMID-23071004 Gold nanograin microelectrodes for neuroelectronic interfaces.

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

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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).

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

PMID-23900251 Parallel super-resolution imaging

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

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

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

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

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

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

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

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

p h(u,v)=sin((a hu/1000+b hv/1000+c h)v+d hu+e hv+f h)+0.97 p_h(u,v) = sin((a_h u/1000 + b_h v/1000 + c_h)v + d_h u + e_h v + f_h) + 0.97 (1)

p v(u,v)=sin((a vu/1000+b vv/1000+c v)u+d vu+e vv+f v)+0.97 p_v(u,v) = sin((a_v u/1000 + b_v v/1000 + c_v)u + d_v u + e_v v + f_v) + 0.97 (2)

I(u,v)=16p hp v/(2+16p h 2+16p v 2) I(u,v) = 16 p_h p_v / ( \sqrt{ 2 + 16 p_h^2 + 16 p_v^2}) (3)

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

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

(a h,b h,d h,e h,f h|a v,b v,d v,e v,f v)=Argmin u v(I(u,v)Img(u,v)) 2 (a_h,b_h,d_h,e_h,f_h | a_v,b_v,d_v,e_v,f_v) = Argmin \sum_u \sum_v (I(u,v) - Img(u,v))^2 (4)

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

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

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

3π2+2πn h=a huv/1000+b hv 2/1000+(c h+e h)v+d hu+f h \frac{3 \pi}{ 2} + 2 \pi n_h = a_h u v/1000 + b_h v^2/1000 + (c_h + e_h)v + d_h u + f_h (5)

3π2+2πn h=a vu 2/1000+b vuv/1000+(c v+d v)u+e vv+f v \frac{3 \pi}{ 2} + 2 \pi n_h = a_v u^2/1000 + b_v u v/1000 + (c_v + d_v)u + e_v v + f_v (6)

Or ..

n h=round((a huv/1000+b hv 2/1000+(c h+e h)v+d hu+f h3π2)/(2π) n_h = round( (a_h u v/1000 + b_h v^2/1000 + (c_h + e_h)v + d_h u + f_h - \frac{3 \pi}{ 2} ) / (2 \pi ) (7)

n v=round((a vu 2/1000+b vuv/1000+(c v+d v)u+e vv+f v3π2)/(2π) n_v = round( (a_v u^2/1000 + b_v u v/1000 + (c_v + d_v)u + e_v v + f_v - \frac{3 \pi}{ 2} ) / (2 \pi) (8)

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

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

u 0=640,v 0=360 u_0 = 640, v_0 = 360

n h=n h,origin| z+[30..30],n v=n v,origin| z+[20..20] n_h = n_{h,origin}|_{z} + [-30 .. 30] , n_v = n_{v,origin}|_{z} + [-20 .. 20] (9)

B i=[3π2+2πn ha hu iv i/1000b hv i 2f h 3π2+2πn va vu i 2/1000b vu iv if v] B_i = {\left[ \begin{matrix} \frac{3 \pi}{ 2} + 2 \pi n_h - a_h u_i v_i / 1000 - b_h v_i^2 - f_h \\ \frac{3 \pi}{ 2} + 2 \pi n_v - a_v u_i^2 / 1000 - b_v u_i v_i - f_v \end{matrix} \right]} (10)

A i=[d h c h+e h c v+d v e v] A_i = {\left[ \begin{matrix} d_h && c_h + e_h \\ c_v + d_v && e_v \end{matrix} \right]} and

[u i+1 v i+1]=mldivide(A i,B i) {\left[ \begin{matrix} u_{i+1} \\ v_{i+1} \end{matrix} \right]} = mldivide(A_i,B_i) (11) where mldivide is the Matlab operator.

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

J i=[a hv i/1000+d h a hu i/1000+2b hv i/1000+c h+e h 2a vu i/1000+b vv i/1000+c v+d v b vu i/1000+e v] J_i = {\left[ \begin{matrix} a_h v_i / 1000 + d_h && a_h u_i / 1000 + 2 b_h v_i / 1000 + c_h + e_h \\ 2 a_v u_i / 1000 + b_v v_i / 1000 + c_v + d_v && b_v u_i / 1000 + e_v \end{matrix} \right]} (12)

K i=[a hu iv i/1000+b hv i 2/1000+(c h+e h)v i+d hu i+f h3π22πn h a vu i 2/1000+b vu iv i/1000+(c v+d v)u i+e vv+f v3π22πn v] K_i = {\left[ \begin{matrix} a_h u_i v_i/1000 + b_h v_i^2/1000 + (c_h+e_h) v_i + d_h u_i + f_h - \frac{3 \pi}{ 2} - 2 \pi n_h \\ a_v u_i^2/1000 + b_v u_i v_i/1000 + (c_v+d_v) u_i + e_v v + f_v - \frac{3 \pi}{ 2} - 2 \pi n_v \end{matrix} \right]} (13)

[u i+1 v i+1]=[u i v i]J i 1K i {\left[ \begin{matrix} u_{i+1} \\ v_{i+1} \end{matrix} \right]} = {\left[ \begin{matrix} u_i \\ v_i \end{matrix} \right]} - J^{-1}_i K_i (14)

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

(u origin| z+0.1u origin| z+0.1) 2+(v origin| z+0.1+v origin| z) 2 (u_{origin}|_{z' + 0.1} - u_{origin}|_{z' + 0.1})^2 + (v_{origin}|_{z' + 0.1} + v_{origin}|_{z'})^2 (15)

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

To this dataset, a model was fit:

[u v]=A[1 x y z x 2 y 2 z 2 w 2 xy xz yz xw yw zw] {\left[ \begin{matrix} u \\ v \end{matrix} \right]} = A {\left[ \begin{matrix} 1 && x && y && z && x'^2 && y'^2 && \prime z'^2 && w^2 && x' y' && x' z' && y' z' && x' w && y' w && z' w \end{matrix} \right]} (16)

Where x=x10x' = \frac{x}{ 10} , y=y10y' = \frac{y}{ 10} , z=z10z' = \frac{z}{ 10} , and w=2020zw = \frac{ 20}{20 - z} . ww was introduced as an axillary variable to assist in perspective mapping, ala computer graphics. Likewise, x,y,zx,y,z were scaled so the quadratic nonlinearity better matched the data.

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

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

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

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

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

A contact lens with embedded sensor for monitoring tear glucose level

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

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

Prioritized experience replay

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Why palladium?


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

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


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

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

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

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

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

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

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


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

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

PMID-24187539 Physical principles for scalable neural recording.

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

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

Weldability of Tungsten and Its Alloys

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

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

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

  • There are problems with parylene multielectrode arrays:
    • water and salts will rapidly diffuse into the various interfacial boundaries
    • Interfacial delamination due to poor wet adhesion of parylene on metal
      • This possibly due to mechanical stress
      • causes excessive cross-talk or noise.
    • Parylene-C devices are prone to poor adhesion at either the dielectric to dielectric interface or at the dielectric to metal interface *** (Sharma and Yasuda 1982; Yasuda et al 2001)
  • solution: PPXCH 2NH 2PPX-CH_2NH_2 and PPXCHOPPX-CHO -- reactive parylene (amine bonds?!)
  • PEDOT is absolutely essential for attaining reasonable performance / impedance from the 85um^2 gold electrodes.
    • Thermal noise on 280um^2 and 170um^2 Au electrodes was too high to record neurons.
    • AU thickness 0.5um.
  • Performed soak tests on their electrodes; the reactive parylene is good, but not sure if it's a worthy improvement.

____References____

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

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

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

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

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

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

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

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

Inductive Rule Learning on the Knowledge Level.

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

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ref: -0 tags: automatic programming date: 05-18-2014 07:02 gmt revision:1 [0] [head]

various:

  • http://www.lighttable.com/2014/05/16/pain-we-forgot/ -- approaching the problem by making better tools / interfaces.
  • http://pchiusano.blogspot.com/2013/05/the-future-of-software-end-of-apps-and.html -- approaching the problem by making the web one giant functional & typed language, distributed over all clients.
    • Strongly advocates the utility and need for typed languages to provide contexts for actions.
    • Interesting, but altogether dreamy and unlikely.
  • Bloom language
    • "the standard data structures in Bloom are disorderly collections, rather than scalar variables and structures. These data structures reflect the realities of non-deterministic ordering inherent in distributed systems. Bloom provides simple, familiar syntax for manipulating these structures. In the Bud prototype, much of this syntax comes straight from Ruby, with a taste of MapReduce and SQL." perfect.
    • From Berkeley.
    • Based on Daedalus data language, which specifies temporal ordering?
      • "The basic idea is that Time (meaning both the sequentiality of program steps in a single “thread”, and coordination of steps across threads/machines) is needed for only one purpose: to prevent multiple possible states from co-occurring. I.e. the purpose of time is to seal fate at each instantaneous moment." src

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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.

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

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

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

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

A damage-tolerant glass

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

{1258}
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ref: -0 tags: polyimide platinum electrodes Spain longitudinal intrafasicular adhesion delamination date: 10-05-2013 22:24 gmt revision:4 [3] [2] [1] [0] [head]

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

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

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

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

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

{1226}
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ref: -0 tags: Kozai carbon nanotube electrode rcording histology date: 08-02-2013 05:42 gmt revision:1 [0] [head]

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

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

{1249}
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ref: -0 tags: retinal ganglion cells neural encoding Farrow date: 07-31-2013 16:21 gmt revision:0 [head]

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

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

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

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

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

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

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

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


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

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


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

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

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

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

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


Update 7/10:

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

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

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

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

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

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

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

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

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

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

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

Environmental Aging and Deadhesion of Polyimide Dielectric films

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

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

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

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

{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)

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

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

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

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

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

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


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

{1232}
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ref: -0 tags: brain mapping recording Yuste date: 04-10-2013 19:31 gmt revision:1 [0] [head]

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

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

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

PMID-23514423 Nanotools for Neuroscience and Brain Activity Mapping

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

{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____

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

IEEE-4065599 (pdf) Comments on Microelectrodes

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

____References____

' ''' ()

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

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

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

____References____

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

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

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

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

____References____

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

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

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

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

____References____

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

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

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

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

____References____

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

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

Things to read!

decoding:

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

electrodes:

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

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

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

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

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

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

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

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

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

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

____References____

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

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

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

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

____References____

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

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

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

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

____References____

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

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

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

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

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

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

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

____References____

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

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

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

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

____References____

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

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

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

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

____References____

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

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

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

____References____

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

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

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

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

____References____

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

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

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

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

____References____

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

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

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

  • Fibers smaller than 6μm6 \mu m show reduced immune response.
    • Fibers implanted in the subcutaneous dorsum (below the skin in the back of rats).
    • Polypropylene. (like rope).
    • Wish the result extended to small beads & small electrodes. 7μm7 \mu m is tiny, but possible with insulated Au wires.
      • Beads: try PMID-1913150 -- shows that the 600um - 50um beads ('microspheres') are well tolerated.
      • Also {750}.
  • Macrophage density in tissue with fiber diameters 2.1-5.9um comparable to that of unoperated contralateral control.

"

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

____References____

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

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

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

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

____References____

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

{897}
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ref: Harris-2011.08 tags: microelectrodes nanocomposite immune response glia recording MEA date: 01-27-2013 22:19 gmt revision:5 [4] [3] [2] [1] [0] [head]

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

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

____References____

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

{1027}
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ref: Suner-2005.12 tags: MEA Utah reliability longevity SNR date: 01-25-2013 02:03 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

PMID-16425835[0] Reliability of signals from a chronically implanted, silicon-based electrode array

  • see {597}
  • Percutaneous connector used pressure-fitted pogo pins, as Gary was thinking of.
  • Utah array coated in parylene for this exp.
    • After implantation, array and cortex was covered in gore-tex (to prevent dura adhesion) -- they do not highlight this fact.
  • polyester insulated 25um gold wires as leads.
  • Reasonable SNR over 82, 172, 154 days.
  • One monkey had an array to 569 days -- 76 electrodes still provided good or fair waveforms.
  • ancilary (?) measure of tuning of the neurons. most neurons were not tuned.
  • SNR calculated as peak-peak of waveform divided by 2x standard deviation of signal.
  • A total of 36 implants in 16 other monkeys, which were not systematically evaluated for reliability here, provided successful recordings for up to 1264 days. Most of these studies ended because of headcap failure.
    • They no longer use dental acrylic -- only titanium bone screws.
  • 50-800K impedance
  • Improvement of the signal quality and increased yield, for which there was no clear trend in the three animals, may result from recovery produced by variations in the initial insertion injury.
  • The cortical capillary bed is densely packed, with spacing on the order of 40um in primate cortical tissue [27] ( vasculature ) -- they suppose that variance may be due to this.

____References____

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

{1198}
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ref: Harris-2011.12 tags: mechanically adaptive electrodes implants case western dissolving flexible histology Harris date: 01-25-2013 01:39 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-22049097[0] Mechanically adaptive intracortical implants improve the proximity of neuronal cell bodies.

  • See also [1]
  • Initial tensile modulus of 5GPa dropped to 12MPa. (almost 500-fold!)
    • Their polymer nanocomposite (NC) still swells 65-70% (with water?)
    • Implant size 100 x 200um.
  • Controlled with tungsten of identical size and coating.
  • Tethered to skull.
  • Interesting:
    • The neuronal nuclei density within 100 µm of the device at four weeks post-implantation was greater for the compliant nanocomposite compared to the stiff wire.
    • At eight weeks post-implantation, the neuronal nuclei density around the nanocomposite was maintained, but the density around the wire recovered to match that of the nanocomposite.
    • Hypothesis, in discussion: softer implants are affecting the time-course of the response rather that final results
  • The glial scar response to the compliant nanocomposite was less vigorous than it was to the stiffer wire
  • Cultured astrocytes have been shown to respond to mechanical stimuli via calcium signaling (Ostrow and Sachs, 2005).
  • Substrate stiffness is also known to shift cell differentiation in mesenchymal stem cells to be neurogenic, myogenic, or osteogenic (Engler et al., 2006).
  • In vivo studies which focus on the effects of electrode tethering have shown that untethered implants reduce the extent of the glial scar (Biran et al., 2007; Kim et al., 2004; Subbaroyan, 2007)
  • Parylene, polymide, and PDMS still each have moduli 6 orders of mangitude larger than that of the brain.
  • In some of their plots, immune response is higher around the nanocomposites!
    • Could be that their implant is still too large / stiff?
  • Note that recent research shows that vitemin may have neuroprotective effects --
    • Research has linked vimentin expression to rapid neurite extension in response to damage (Levin et al., 2009)
    • NG2+ cells that express vimentin have been proposed to support repair of central nervous system (CNS) damage, and stabilize axons in response to dieback from ED1+ cells (Alonso, 2005; Nishiyama, 2007; Busch et al., 2010)
  • Prior work (Frampton et al., 2010 PMID-20336824[2]) hypothesizes that a more compact GFAP response increases the impedance of an electrode which may decrease the quality of electrode recordings.

____References____

[0] Harris JP, Capadona JR, Miller RH, Healy BC, Shanmuganathan K, Rowan SJ, Weder C, Tyler DJ, Mechanically adaptive intracortical implants improve the proximity of neuronal cell bodies.J Neural Eng 8:6, 066011 (2011 Dec)
[1] Harris JP, Hess AE, Rowan SJ, Weder C, Zorman CA, Tyler DJ, Capadona JR, In vivo deployment of mechanically adaptive nanocomposites for intracortical microelectrodes.J Neural Eng 8:4, 046010 (2011 Aug)
[2] Frampton JP, Hynd MR, Shuler ML, Shain W, Effects of glial cells on electrode impedance recorded from neuralprosthetic devices in vitro.Ann Biomed Eng 38:3, 1031-47 (2010 Mar)

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ref: Lewitus-2011.08 tags: dissolving polymer electrodes histology degrading date: 01-25-2013 01:31 gmt revision:2 [1] [0] [head]

PMID-21609850[0] The fate of ultrafast degrading polymeric implants in the brain.

  • Tyrosene-derived terpolymer (protein?) dissolves within hours & was re-absorbed.
  • Second terpolymer degrades quickly but is not resorbed.
    • This type resulted in continuous glial activation and loss of neural tissue compared to first.
  • Makes sense, not unexpected.

____References____

[0] Lewitus DY, Smith KL, Shain W, Bolikal D, Kohn J, The fate of ultrafast degrading polymeric implants in the brain.Biomaterials 32:24, 5543-50 (2011 Aug)

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ref: Rennaker-2005.03 tags: electrode recording longevity mechanical insertion Oklahoma MEA date: 01-25-2013 01:21 gmt revision:3 [2] [1] [0] [head]

PMID-15698656[0] A comparison of chronic multi-channel cortical implantation techniques: manual versus mechanical insertion.

  • Over 60% of the animals implanted with the mechanical insertion device had driven activity at week 6
    • whereas none of the animals with manually inserted arrays exhibited functional responses after 3 weeks.
      • Roughly identical responses immediately following surgery.
      • Could be that the manual inserter had horizontal movement / shear. (This is solveable with a stereotax).
      • Other research showed little difference in tissue response at 10um/s or 100um/s PMID-21896383[1]
  • Multi-wire electrodes.
  • Mechanical insertion device was capable of rapidly inserting the electrode without visible compression of the brain.
  • Response measured relative to auditory stimulus.
  • Their insertion device looks like a pen.

____References____

[0] Rennaker RL, Street S, Ruyle AM, Sloan AM, A comparison of chronic multi-channel cortical implantation techniques: manual versus mechanical insertion.J Neurosci Methods 142:2, 169-76 (2005 Mar 30)
[1] Welkenhuysen M, Andrei A, Ameye L, Eberle W, Nuttin B, Effect of insertion speed on tissue response and insertion mechanics of a chronically implanted silicon-based neural probe.IEEE Trans Biomed Eng 58:11, 3250-9 (2011 Nov)

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ref: -0 tags: Shenoy eye position BMI performance monitoring date: 01-25-2013 00:41 gmt revision:1 [0] [head]

PMID-18303802 Cortical neural prosthesis performance improves when eye position is monitored.

  • This proposal stems from recent discoveries that the direction of gaze influences neural activity in several areas that are commonly targeted for electrode implantation in neural prosthetics.
  • Can estimate eye position directly from neural activity & subtract it when performing BMI predictions.

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ref: -0 tags: flexible polymer electrode recording polypyrrole Bizzi date: 01-25-2013 00:39 gmt revision:0 [head]

PMID-19164034 Cortical recording with polypyrrole microwire electrodes.

  • http://web.mit.edu/bcs/bizzilab/publications/bae2008.pdf
  • Electropolymerization of PPy on a glassy carbon electrode in solution.
  • Polypyrrole microwires were prepared by mounting a PPy film perpendicular to the stage of a cryo-microtome and slicing it in 20um sections.
  • Electrode mounted inside a glass capillary tube.
  • Impedance: 1e5 @ 1kHz.

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ref: Stice-2007.06 tags: electrodes recording small rats S1 PGA histology GFAP date: 01-24-2013 21:07 gmt revision:9 [8] [7] [6] [5] [4] [3] [head]

PMID-17409479[0] Thin microelectrodes reduce GFAP expression in the implant site in rodent somatosensory cortex.

  • Implanted 12 um and 25 um polymide coated stainless steel
    • Wires coated with poly-glycolic acid (PGA) to facilitate implantation.
  • Only looked to 4 weeks.
  • 12 um implants significantly less GFAP (astrocyte) reactivity at 4 weeks, no difference at 2 weeks (figure 9 & 10).
    • B = bare, P = PGA coated.
  • Can use to bolster the idea that smaller implants are less irritating.

____References____

[0] Stice P, Gilletti A, Panitch A, Muthuswamy J, Thin microelectrodes reduce GFAP expression in the implant site in rodent somatosensory cortex.J Neural Eng 4:2, 42-53 (2007 Jun)

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ref: Biran-2007.07 tags: tresco biocompatibility tether skull electrodes Michigan probe recording Tresco date: 01-24-2013 20:11 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

PMID-17266019[0] The brain tissue response to implanted silicon microelectrode arrays is increased when the device is tethered to the skull.

  • Good, convincing, figures.

____References____

[0] Biran R, Martin DC, Tresco PA, The brain tissue response to implanted silicon microelectrode arrays is increased when the device is tethered to the skull.J Biomed Mater Res A 82:1, 169-78 (2007 Jul)

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ref: Ganguly-2011.05 tags: Carmena 2011 reversible cortical networks learning indirect BMI date: 01-23-2013 18:54 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

PMID-21499255[0] Reversible large-scale modification of cortical networks during neuroprosthetic control.

  • Split the group of recorded motor neurons into direct (decoded and controls the BMI) and indirect (passive) neurons.
  • Both groups showed changes in neuronal tuning / PD.
    • More PD. Is there no better metric?
  • Monkeys performed manual control before (MC1) and after (MC2) BMI training.
    • The majority of neurons reverted back to original tuning after BC; c.f. [1]
  • Monkeys were trained to rapidly switch between manual and brain control; still showed substantial changes in PD.
  • 'Near' (on same electrode as direct neurons) and 'far' neurons (different electrode) showed similar changes in PD.
    • Modulation Depth in indirect neurons was less in BC than manual control.
  • Prove (pretty well) that motor cortex neuronal spiking can be dissociated from movement.
  • Indirect neurons showed decreased modulation depth (MD) -> perhaps this is to decrease interference with direct neurons.
  • Quote "Studies of operant conditioning of single neurons found that conconditioned adjacent neurons were largely correlated with the conditioned neurons".
    • Well, also: Fetz and Baker showed that you can condition neurons recorded on the same electrode to covary or inversely vary.
  • Contrast with studies of motor learning in different force fields, where there is a dramatic memory trace.
    • Possibly this is from proprioception activating the cerebellum?

Other notes:

  • Scale bars on the waveforms are incorrect for figure 1.
  • Same monkeys as [2]

____References____

[0] Ganguly K, Dimitrov DF, Wallis JD, Carmena JM, Reversible large-scale modification of cortical networks during neuroprosthetic control.Nat Neurosci 14:5, 662-7 (2011 May)
[1] Gandolfo F, Li C, Benda BJ, Schioppa CP, Bizzi E, Cortical correlates of learning in monkeys adapting to a new dynamical environment.Proc Natl Acad Sci U S A 97:5, 2259-63 (2000 Feb 29)
[2] Ganguly K, Carmena JM, Emergence of a stable cortical map for neuroprosthetic control.PLoS Biol 7:7, e1000153 (2009 Jul)

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ref: Chestek-2009.09 tags: BMI problems address critique spike sorting Shenoy date: 01-23-2013 02:23 gmt revision:3 [2] [1] [0] [head]

IEEE-5332822 (pdf) Neural prosthetic systems: Current problems and future directions

  • Where there is unlikely to be improvements: spike sorting and spiking models.
  • Where there are likely to be dramatic improvements: non-stationarity of recorded waveforms, limitations of a linear mappings between neural activity and movement kinematics, and the low signal to noise ratio of the neural data.
  • Compare different sorting methods: threshold, single unit, multiunit, relative to decoding.
  • Plot waveform changes over an hour -- this contrasts with earlier work (?) {1032}
  • Figure 5: there is no obvious linear transform between neural activity and the kinematic parameters.
  • Suggest that linear models need to be replaced by the literature of how primates actually make reaches.
  • Discuss that offline performance is not at all the same as online; in the latter the user can learn and adapt on the fly!

____References____

Chestek, C.A. and Cunningham, J.P. and Gilja, V. and Nuyujukian, P. and Ryu, S.I. and Shenoy, K.V. Engineering in Medicine and Biology Society, 2009. EMBC 2009. Annual International Conference of the IEEE 3369 -3375 (2009)

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ref: -2002 tags: sea slugs flexible electrodes polymide Washington date: 01-04-2013 18:46 gmt revision:0 [head]

IEEE-1002325 (pdf) Silicon micro-needles with flexible interconnections

  • Implanted their isolated needles (see also {219}) in sea slugs Tritonia diomedea
    • Sea slug neurons are large -- up to 400um -- makes recording easier.
  • Silicon needles fabricated via reactive ion etching and SF6 sharpening.
  • 'intracellular recording!
  • Pretty advanced fabrication, I guess.

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ref: Du-2011.01 tags: Harrison recording electrode MEA Blanche date: 01-04-2013 02:43 gmt revision:3 [2] [1] [0] [head]

PMID-22022568[0] Multiplexed, High Density Electrophysiology with Nanofabricated Neural Probes

  • The number of single-units possible to record doubles every 7 years [5].
  • Electrodes must be within 100um of soma to relaibly detect extracellular action potentials.
  • Existing Michigan arrays have trace features around >=1 um; here they use E-beam lithography to decrease the probe width dramatically.
    • Their wire widths are 290 nm. Still bigger than 40nm process (?)
  • Seem to use Reid Harrison's ASIC RHA22132 design.
  • noise of electrodes progressively decreased with consecutive gold electroplating cycles. Plating makes the electrodes rough, and decreases their impedance to around 1 M.
    • Electrode contacts are around 10 x 10 um square, 108 um^2 area.
  • Intrinsic noise of the amplifier 1.7 uV RMS.
  • 290 nm wire had an impedance of 9.2 k -- corresponding to 1.0 uV rms noise.
  • able to record from the same neuron from several adjacent electrodes. Spacing ~ 28 um.
  • Detail their process extensively -- 40% of probes survived the process with <= 5 defective channels. THey propose further optimization to the e-beam lithography. Probes took 7 hours to pattern on the lithography machine (!).

____References____

[0] Du J, Blanche TJ, Harrison RR, Lester HA, Masmanidis SC, Multiplexed, high density electrophysiology with nanofabricated neural probes.PLoS One 6:10, e26204 (2011)

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ref: -0 tags: flexible micxrowire arrays electrode recording Georgia polymide date: 01-04-2013 00:13 gmt revision:1 [0] [head]

IEEE-906517 (pdf) Flexible microelectrode arrays with integrated insertion devices

  • 2001 MEMS Conference.
  • FMA = flexible microelectrode arrays.
  • Both for nerves (pass-through needle) and cortex (removeable needle).
    • Primarily tested in tissue proxies.
  • Anticipated the utility of photolithography for patterning the electrodes + rigid insertion devices.
  • The elastic modulus of polymers like polymide are two orders of magnitude less than metals, but still six orders of magnitude higher than brain tissue (46kPa).
  • Pass-through needle very similar to the threaded wire idea.
  • removable needle simply stops the thread & drives the needle a bit further to break the attachment site.
    • Did not test removable needle technique (?)
  • Defined electroplating with a thick photoresist mask, as Michel says.
  • Tested FMAs with movement and acceleration vs. rigid arrays. FMAs faired much better, of course!

____References____

' ''' ()

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ref: -0 tags: parylene flexible neural recording drug delivery microfluidics 2012 inserter needle release date: 01-02-2013 22:41 gmt revision:1 [0] [head]

PMID-23160191 Novel flexible Parylene neural probe with 3D sheath structure for enhancing tissue integration

  • They seem to think that drugs are critical for success: "These features will enhance tissue integration and improve recording quality towards realizing reliable chronic neural interfaces."
  • Similar to Kennedy: "The sheath structure allows for ingrowth of neural processes leading to improved tissue/probe integration post implantation." 8 electrodes, 4 on the cone interior, 4 on the exterior.
    • opening is 50um at tip, 300 um at base.
  • Used a PEEK-stiffened parylene ZIF connection.
  • Only tested in agarose, but it did properly release from the inserter needle.
  • I wonder if we could use a similar technique..
  • "Lab on a chip" journal (Royal society of Chemistry). nice.

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ref: -0 tags: neural recording topologies circuits operational transconductance amplifiers date: 01-02-2013 20:00 gmt revision:0 [head]

PMID-22163863 Recent advances in neural recording microsystems.

  • Decent review. Has some depth on the critical first step of amplification.

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ref: -0 tags: optical neural recording photon induced electron transfer date: 01-02-2013 04:25 gmt revision:2 [1] [0] [head]

PMID-22308458 Optically monitoring voltage in neurons by photo-induced electron transfer through molecular wires.

  • Photoinduced electron transfer.
    • About what you would think -- a photon bumps an electron into a higher orbital, and this electron can be donated to another group or drop back down & fluoresce a photon.
  • Good sensitivity: ΔF/F\Delta F/F of 20-27% per 100mV, fast kinetics.
  • Not presently genetically targetable.
  • Makes sense in terms of energy: "A 100-mV depolarization changes the PeT driving force by 0.05 eV (one electron × half of 100-mV potential, or 0.05 V). Because PeT is a thermally controlled process, the value of 0.05 eV is large relative to the value of kT at 300 K (0.026 eV), yielding a large dynamic range between the rates of PeT at resting and depolarized potentials.
  • Why electrochromic dyes have plateaued:
    • "In contrast, electrochromic dyes have smaller delta G values, 0.003 (46) to 0.02 (47) eV, and larger comparison energies. Because the interaction is a photochemically controlled process, the energy of the exciting photon is the comparison energy, which is 1.5–2 eV for dyes in the blue-to-green region of the spectrum. Therefore, PeT and FRET dyes have large changes in energy versus their comparison energy (0.05 eV vs. 0.026 eV), giving high sensitivities; electrochromic dyes have small changes compared with the excitation photon (0.003–0.02 eV vs. 2 eV), producing low voltage sensitivity."

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ref: -0 tags: optical imaging neural recording diamond magnetic date: 01-02-2013 03:44 gmt revision:0 [head]

PMID-22574249 High spatial and temporal resolution wide-field imaging of neuron activity using quantum NV-diamond.

  • yikes: In this work we consider a fundamentally new form of wide-field imaging for neuronal networks based on the nanoscale magnetic field sensing properties of optically active spins in a diamond substrate.
  • Cultured neurons.
  • NV = nitrogen-vacancy defect centers.
    • "The NV centre is a remarkable optical defect in diamond which allows discrimination of its magnetic sublevels through its fluorescence under illumination. "
    • We show that the NV detection system is able to non-invasively capture the transmembrane potential activity in a series of near real-time images, with spatial resolution at the level of the individual neural compartments.
  • Did not actually perform neural measurements -- used a 10um microwire with mA of current running through it.
    • I would imagine that actual neurons have far less current!

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ref: -0 tags: optical recording voltage sensitive dyes redshirt date: 01-02-2013 03:17 gmt revision:3 [2] [1] [0] [head]

PMID-16050036 Imaging brain activity with voltage- and calcium-sensitive dyes.

  • Voltage-sensitive dyes are well suited for measuring synaptic integration, as:
    • Electrodes are too blunt to effectively record these fine, < 1um diameter structures.
    • The surface area to volume ratio is highest in the dendrites
    • Voltage-sensitive dyes also permeate internal membranes not subject to voltage gradients, hence this does not contribute to the signal, leading to a decreased ΔF/F\Delta F / F .
  • Dominant experimental noise is shot noise, statistical -- see {1181}.
  • modern dyes and imagers can reliably record single action potentials; spatial averaging yields similar resolution as electrical recording.
  • They performed optical recording of Aplysia sensory ganglia, and discovered following light tail touch: "It is almost as if the Aplysia nervous system is designed such that every cell in the abdominal ganglion cares about this (and perhaps every) sensory stimulus. In addition, more than 1000 neurons in other ganglia are activated by this touch..."
      • These results force a more pessimistic view of the present understanding of the neuronal basis of apparently simple behaviors in relatively simple nervous systems.
  • Used calcium imaging on olfactory glomeruli of mice and turtles; measurements were limited by either shot-noise or heart/breathing artifacts.
  • Confocal and two-photon microscopes, due to their exchange of spatial resolution for sensitivity, are not useful with voltage-sensitive dyes.
    • The generation of fluorescent photons in the 2-photon confocal microscope is not efficient. We compared the signals from Calcium Green-1 in the mouse olfactory bulb using 2-photon and ordinary microscopy. In this comparison the number of photons contributing to the intensity measurement in the 2-photon confocal microscope was about 1000 times smaller than the number measured with the conventional microscope and a CCD camera.
  • By the numbers, quote: Because only a small fraction of the 10e16 photons/ms emitted by a tungsten filament source will be measured, a signal-to-noise ratio of 10e8 (see above) cannot be achieved. A partial listing of the light losses follows. A 0.9-NA lamp collector lens would collect 0.1 of the light emitted by the source. Only 0.2 of that light is in the visible wavelength range; the remainder is infrared (heat). Limiting the incident wavelengths to those, which have the signal means, that only 0.1 of the visible light is used. Thus, the light reaching the
preparation might typically be reduced to 1013 photons/ms. If the light-collecting system that forms the image has high efficiency e.g., in an absorption measurement, about 1013 photons/ms will reach the image plane. (In a fluorescence measurement there will be much less light measured because 1. only a fraction of the incident photons are absorbed by the fluorophores, 2. only a fraction of the absorbed photons appear as emitted photons, and 3. only a fraction of the emitted photons are collected by the objective.) If the camera has a quantum efficiency of 1.0, then, in absorption, a total of 10e13 photoelectrons/ms will be measured. With a camera of 1000 pixels, there will be 10e10 photoelectrons/ms/pixel. The shot noise will be 10e5 photoelectrons/ms/pixel; thus the very best that can be expected is a noise that is 10e−5 of the resting light (a signal-to-noise ratio of 100 db). The extra light losses in a fluorescence measurement will further reduce the maximum obtainable signal-to-noise ratio.

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ref: -0 tags: neural imaging recording shot noise redshirt date: 01-02-2013 02:20 gmt revision:0 [head]

http://www.redshirtimaging.com/redshirt_neuro/neuro_lib_2.htm

  • Shot Noise: The limit of accuracy with which light can be measured is set by the shot noise arising from the statistical nature of photon emission and detection.
    • If an ideal light source emits an average of N photons/ms, the RMS deviation in the number emitted is N\sqrt N .
    • At high intensities this ratio NN\frac{N}{\sqrt N} is large and thus small changes in intensity can be detected. For example, at 10^10 photons/ms a fractional intensity change of 0.1% can be measured with a signal-to-noise ratio of 100.
    • On the other hand, at low intensities this ratio of intensity divided by noise is small and only large signals can be detected. For example, at 10^4 photons/msec the same fractional change of 0.1% can be measured with a signal-to-noise ratio of 1 only after averaging 100 trials.

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ref: -0 tags: optical coherence tomography neural recording squid voltage sensitive dyes review date: 12-23-2012 21:00 gmt revision:4 [3] [2] [1] [0] [head]

PMID-20844600 Detection of Neural Action Potentials Using Optical Coherence Tomography: Intensity and Phase Measurements with and without Dyes.

  • Optical methods of recording have been investigated since the 1940's:
    • During action potential (AP) propagation in neural tissue light scattering, absorption, birefringence, fluorescence, and volume changes have been reported (Cohen, 1973).
  • OCT is reflection-based, not transmission: illuminate and measure from the same side.
    • Here they use spectral domain OCT, where the mirror is not scanned; rather SD-OCT uses a spectrometer to record interference of back-scattered light from all depth points simultaneously (Fercher et al., 1995).
    • Use of a spectrometer allows imaging of an axial line within 10-50us, sufficient for imaging action potentials.
    • SD-OCT, due to some underlying mathematics which I can't quite grok atm, can resolve/annul common-mode phase noise for high temporal and Δphase\Delta phase measurement (high sensitivity).
      • This equates to "microsecond temporal resolution and sub-nanometer optical path length resolution".
  • OCT is generally (intially?) used for in-vivo imaging of retinas, in humans and other animals.
  • They present new data for depth-localization of neural activity in squid giant axons (SGA) stained with a voltage-sensitive near-infrared dye.
    • Note: averaged over 250 sweeps.
  • ΔPhase>>ΔIntensity\Delta Phase &gt;&gt; \Delta Intensity -- figure 4 in the paper.
  • Use of voltage-sensitive dyes improves the resolution of ΔI\Delta I , but not dramatically --
    • And Δphase\Delta phase is still a bit delayed.
    • Electrical recording is the control.
      • It will take significant technology development before optical methods exceed electrical methods...
  • Looks pretty preliminary. However, OCT can image 1-2mm deep in transparent tissue, which is exceptional.
  • Will have to read their explanation of OCT.
  • Used in a squid giant axon prep. 2010, wonder if anything new has been done (in vivo?).
  • Claim that progress is hampered by limited understanding of how these Δphase\Delta phase signals arise.

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ref: -0 tags: optical coherence tomography neural recording aplysia date: 12-23-2012 09:12 gmt revision:2 [1] [0] [head]

PMID-19654752 Detecting intrinsic scattering changes correlated to neuron action potentials using optical coherence imaging.

  • Aplysia, intrinsic imaging of scattering change following electrical stimulation.
    • Why did it take so long for them to get this paper out.. ?
  • Nicolelis first cited author.
  • Quality of recording not necessarily high.
  • quote: "Typical transverse resolutions in OCT (10-20um) are likely insufficient to identify smaller mamallian neurons that are often studied in neuroscience."
    • Solution: optical coherence microscopy (OCM), where a higher NA lens focuses the light to a smaller spot.
    • Expense: shorter depth-of-field.
  • Why does this work? "One mechanism of these optical signals is believed to be a realignment of charged membrane proteins in response to voltage change [6].
  • A delay of roughly 70ms was observed between the change in membrane voltage and the change in scattering intensity.
    • That's slow! Might be due to conduction velocity in Aplysia.
  • SNR of scattering measurement not too high -- the neurons are alive, afterall, and their normal biological processes cause scattering changes.
    • Killing the neurons with KCl dramatically decreased the variance of scattering, consistent with this hpothesis.
  • Birefringence: "Changes in the birefringence of nerves due to electrical activity have been shown to be an order of magnitude larger than scattering intensity changes" PMID-5649693

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ref: -0 tags: Moshe looks automatic programming google tech talk links date: 11-07-2012 07:38 gmt revision:3 [2] [1] [0] [head]

List of links from Moshe Looks google tech talk:

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ref: -0 tags: matlab STL boost programming C++ date: 11-06-2012 21:58 gmt revision:2 [1] [0] [head]

Recently decided to move myopen's sorting program from sqlite-based persistent state to matlab persistent state, for better interoperability with lab rigs & easier introspection. For this I wrote a class for serializing STL / boost based one, two, and three dimensional resizeable containers to and from matlab files.

The code has been tested (albeit not extensively), and therefore may be of use to someone else, even if as an example. See: http://code.google.com/p/myopen/source/browse/trunk/common_host/matStor.cpp

As you can see from the header (below), the interface is nice and concise!

#ifndef __MATSTOR_H__
#define __MATSTOR_H__

class MatStor{
        typedef boost::multi_array<float, 3> array3; 
        typedef boost::multi_array<float, 2> array2; 
        
        std::string m_name; //name of the file.
        std::map<std::string, std::vector<float> > m_dat1; //one dimensional
        std::map<std::string, array2> m_dat2; //two dimensions
        std::map<std::string, array3> m_dat3; //three!
public:
        MatStor(const char* fname); 
        ~MatStor(); 
        void save(); 
        void setValue(int ch, const char* name, float val);
        void setValue2(int ch, int un, const char* name, float val);
        void setValue3(int ch, int un, const char* name, float* val, int siz);
        float getValue(int ch, const char* name, float def);
        float getValue2(int ch, int un, const char* name, float def);
        void getValue3(int ch, int un, const char* name, float* val, int siz);
}; 
#endif

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ref: -0 tags: Zador Peikon cold spring plos date: 11-06-2012 19:46 gmt revision:1 [0] [head]

Sequencing the Connectome

  • Quote: "Interestingly, the utility of the connectome in C. elegans is somewhat limited because function is highly multiplexed, with different neurons performing different roles depending on the state of neuromodulation [7], possibly as a mechanism for compensating for the small number of neurons."
  • In comparison, the authors argue that the role of neurons in mammalian brains is much more highly determined by connectivity / physical location, and support this with examples from the visual system (area MT; how layer in V1 determines simple vs. complex tuning).
  • Only have started work on this highly ambitious project -- current plan is to use PRV amplicons for permuting the neuronal barcodes -- and offer no results, just the general framework of the idea.
    • Given that Ian spoke of the idea when he first started at CSH, I wonder just how practical this idea is?

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ref: -0 tags: artificial intelligence projection episodic memory reinforcement learning date: 08-15-2012 19:16 gmt revision:0 [head]

Projective simulation for artificial intelligence

  • Agent learns based on memory 'clips' which are combined using some pseudo-bayesian method to trigger actions.
    • These clips are learned from experience / observation.
    • Quote: "..more complex behavior seems to arise when an agent is able to “think for a while” before it “decides what to do next.” This means the agent somehow evaluates a given situation in the light of previous experience, whereby the type of evaluation is different from the execution of a simple reflex circuit"
    • Quote: "Learning is achieved by evaluating past experience, for example by simple reinforcement learning".
  • The forward exploration of learned action-stimulus patterns is seemingly a general problem-solving strategy (my generalization).
  • Pretty simple task:
    • Robot can only move left / right; shows a symbol to indicate which way it (might?) be going.

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ref: -0 tags: filtering spike sorting AUC ROC r date: 08-08-2012 23:35 gmt revision:12 [11] [10] [9] [8] [7] [6] [head]

A frequent task in the lab is to sort spikes (extracellular neural action potentials) from background noise. In the lab we are working on doing this wirelessly; to minimize power consumption, spike sorting is done before the radio. In this way only times of spikes need be transmitted, saving bandwidth and power. (This necessitates a bidirectional radio protocol, but this is a worthy sacrifice).

In most sorting programs (e.g. Plexon), the raw signal is first thresholded, then waveform snippets (typically 32 samples long) are compared to a template to accept/reject them, or to sort them into different units. The comparison metric is usually the mean-squared error, MSE, aka the L2 norm. This makes sense, as the spike shapes are assumed to be stereotyped (they may very well not be), and the noise white / uncorrelated (another debatable assumption).

On the headstage we are working with for wireless neural recording, jumps and memory moves are expensive operations, hence we've elected to do no waveform extraction, and instead match continuously match. By using the built-in MPEG compression opcodes, we can compute the L1 norm at a rate of 4 samples / clock -- very efficient. However, this was more motivated by hardware considerations an not actual spike sorting practice. Literature suggests that for isolating a fixed-pattern signal embedded in noise, the best solution is instead a matched filter.

Hence, a careful study of spike-sorting was attempted in matlab, given the following assumptions: fixed spike shape (this was extracted from real data), and uncorrelated band-limited noise. The later was just white noise passed through a bandpass filter, e.g.

cheby1(3, 2, [500/15e3 7.5/15])

Where the passband edges are 500 Hz and 15kHz, at a sampling rate of 30kHz. (Actual rate is 31.25kHz). Since the spike times are known, we can rigorously compare the Receiver Operating Characteristic (ROC) and the area under curve (AUC) for different sorting algorithms. Four were tried: L1 (as mentioned above, motivated by the MPEG opcodes), L2 (Plexon), FIR matched filter, and IIR matched filter.

The latter was very much an experiment -- IIR filters are efficiently implemented on the blackfin processor, and they generally require fewer taps than their equivalent FIR implementation. To find an IIR equivalent to a given FIR matched filter (whose impulse response closely looks like the actual waveshape, just time-reversed), the filter parameters were simply optimized to match the two impulse responses. To facilitate the search, the denominator was specified in terms of complex conjugate pole locations (thereby constraining the form of the filter), while the numerator coefficients were individually optimized. Note that this is not optimizing given the objective to maximize sorting quality -- rather, it is to make the IIR filter impulse response as close as possible to the FIR matched filter, hence computationally light.

And yet: the IIR filter outperforms the FIR matched filter, even though the IIR filter has 1/3 the coefficients (10 vs 32)! Below is the AUC quality metric for the four methods.

And here are representative ROC curves at varying spike SNR ratios.

The remarkable thing is that even at very low SNR, the matched IIR filter can reliably sort cells from noise. (Note that the acceptable false positive here should be weighted more highly; in the present analysis true positive and false positive are weighted equally, which is decidedly non-Bayesian given most of the time there is no spike.) The matched IIR filter is far superior to the normal MSE to template / L2 norm method -- seems we've been doing it wrong all along?

As for reliably finding spikes / templates / filters when the SNR < 0, the tests above - which assume an equal number of spike samples and non-spike samples -- are highly biased; spikes are not normally sortable when the SNR < 0.


Upon looking at the code again, I realized three important things:

  1. The false positive rate need to be integrated over all time where there is no spike, just the same as the true positive is over all time where there is a spike.
  2. All methods need to be tested with 'distractors', or other spikes with a different shape.
  3. The FIR matched filter was backwards!

Including #1 above, as expected, dramatically increased the false positive rate, which is to be expected and how the filters will be used in the real world. #2 did not dramatically impact any of the discriminators, which is good. #3 alleviated the gap between the IIR and FIR filters, and indeed the FIR matched filter performance now slightly exceeds the IIR matched filer.

Below, AUC metric for 4 methods.

And corresponding ROC for 6 different SNR ratios (note the SNRs sampled are slightly different, due to the higher false positive rate).

One thing to note: as implemented, the IIR filter requires careful matching of poles and zeros, and is may not work with 1.15 fixed-point math on the Blackfin. The method really deserves to be tested in vivo, which I shall do shortly.


More updates:

See www.aicit.org/jcit/ppl/JCIT0509_05.pdf -- they add an 'adjustment' function to the matched filter due to variance in the amplitude of spikes, which adds a little performance at low SNRs.

F(t)=[x(t)kσe˙ 1x(t)kσ] n F(t) = \left[ \frac{x(t)}{k \sigma} \dot e^{1-\frac{x(t)}{k \sigma}} \right]^n

Sigma is the standard deviation of x(t), n and k determine 'zoom intensity and zoom center'. The paper is not particularly well written - there are some typos, and their idea seems unjustified. Still the references are interesting:

  • IEEE-238472 (pdf) Optimal detection, classification, and superposition resolution in neural waveform recordings.
    • Their innovation: whitening filter before template matching, still use L2 norm.
  • IEEE-568916 (pdf) Detection, classification, and superposition resolution of action potentials in multiunit single-channel recordings by an on-line real-time neural network
    • Still uses thresholding / spike extraction and L2 norm. Inferior!
  • IEEE-991160 (pdf) Parameter estimation of human nerve C-fibers using matched filtering and multiple hypothesis tracking
    • They use a real matched filter to detect extracellular action potentials.


Update: It is not to difficult to convert FIR filters to IIR filters using simple numerical optimization. Within my client program, this is done using simulated annealing; have tested this using fminsearch in matlab. To investigate the IIR-filter fitting problem more fully, I sliced the 10-dimensional optimization space along pairs of dimensions about the optimum point as found using fminsearch.

The parameters are as follows:

  1. Two poles, stored as four values (a real and imaginary part for each pole pair). These are expanded to denominator coefficients before evaluating the IIR filter.
  2. Five numerator coeficients.
  3. One delay coefficient (to match the left/right shift).

The figure below plots the +-1 beyond the optimum for each axis pair. Click for full resolution image. Note that the last parameter is discrete, hence steps in the objective function. Also note that the problem is perfectly quadratic for the numerator, as expected, which is why LMS works so well.

Note that for the denominator pole locations, the volume of the optimum is small, and there are interesting features beyond this. Some spaces have multiple optima.

The next figure plots +-0.1 beyond the optimum for each axis vs. every other one. It shows that, at least on a small scale, the problem becomes very quadratic in all axes hence amenable to line or conjugate gradient search.

Moving away from planes that pass through a found optima, what does the space look like? E.g. From a naive start, how hard is it to find at least one workable solution? To test this, I perturbed the found optimum with white noise in the parameters std 0.2, and plotted the objective function as before, albeit at higher resolution (600 x 600 points for each slice).

These figures show that there can be several optima in the denominator, but again it appears that a very rough exploration followed by gradient descent should arrive at an optima.

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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}

{1164}
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ref: -0 tags: neural recording McGill Musallam electrodes date: 07-12-2012 22:53 gmt revision:0 [head]

http://www.mdpi.com/1424-8220/8/10/6704/pdf NeuroMEMS: Neuro Probe Microtechnologies

  • Good review (as of 2008) of the many different approaches for nervous system recording.

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ref: Rousche-1998.07 tags: BMI Utah cat Normann recording electrode MEA histology date: 06-29-2012 01:12 gmt revision:9 [8] [7] [6] [5] [4] [3] [head]

PMID-10223510 Chronic recording capability of the Utah Intracortical Electrode Array in cat sensory cortex.

  • Focus on (surprisingly) chronic recording from the utah array: they want to demonstrate that it works.
  • Platinum coating.
  • insulated with 2-3um polymide.
  • 10 cats, 12 arrays: 2 in S1, 8 in auditory ctx, 2 V1.
  • 11 electrodes connected in each array.
  • After a 6-month implant period, 60% of implanted arrays could still record 'some type of activity'.
  • They were completely targeting neuroprostheses.
    • But acknowledge that 'the presence of fibrous encapsulation and chronic astrogliosis suggests that more research is necessary before the UIEA can be uses as a cornerstone of a neuroprosthetic device for human use.
      • And yet they went through with the human trials?
  • Electrode impedance gave no hint as to the ability of a given electrode to record neural units: many electrodes with average impedance could not record neural activity.
  • Impedances generally decreased , which is not unusual (Schmidt and Bak, 1976).
    • Likely that the polymide had become permeated with water vapor to and equilibrium point. (rather than pinhole leaks or water permeation).
  • Quiet amplifiers: 2uv pk-pk.
  • No significant trend in background activity was noted over the implant durations.
  • In nearly every cat, the dura above the electrode array adhered to the bone flap, and the electrode array adhered to the dura. Therefore, when the bone flap was removed, the UIEA was concurrently explanted from the cortex.
    • Similar to Hoogerwerf and Wise 1994 {1025}
    • The explanted UIEAs typically had become encapsulated, the encapsulation was the cause of the cortical depression.
    • Only 1 did not become encapsulated in dura.
    • This encapsulation explains the gradually varying recording properties -- the electrodes were moving out of the brain.
    • "The capsule which formed around the substrate of the UIEA was usually continuous with the dura, which was enmeshed directly to the overlying skull. The encapsulated array therefore had no freedom of movement with respect to the skull, and this may have caused local trauma which reduced the possibility of recording neural activity. This relative micromovement between the fixed array and the ‘floating’ cortical tissue may also be responsible for sustaining continued growth of the encapsulation as described above."
    • Have tried putting teflon on the top of the Utah array -- did this work?
  • Two UIEAs were not found near the cortical surface -- these two arrays were totally removed from the leptomeningeal space. although originally implanted into the cortex beneath the dura, at the time of sacrafice these arrays were found above the repaired dura, and the implanted cortex showed no evicence of cortical implant.
  • Some electrodes healthy; other showed chronic inflammation.
  • General and intense inflamation in the upper layers of cortex even on their best-performing array; no guarantee that this ctx was working properly, as it is heavily compressed with fibroblasts.
  • Regarding vascluature, see {1024}.
  • Say that the largest impediment is the formation of a capsule around the implant. (Do not mention issue of infection; I guess cats have strong immune systems as well?)
  • Rather good biological discussion and conclusion. worth a re-read. "We currently recommend that the UIEA be used for acute and short-term applications."
    • Not too many follow-ups re teflon or fixing the encapsulation problem: See {1026}
      • Indeed, {1027} doesn't even cite this! Too disastrous?

____References____

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ref: -0 tags: springfield downtown library health society date: 05-27-2012 00:44 gmt revision:0 [head]

Just to my left, a woman in a walker rolled into the library, and promptly complained to the police officer on duty about chest pains. The library faces a square in the middle of Springfield where teenagers, shirtless hippies, skateboarders, and other non-mainstream people kill time in the warm afternoon. The library as such is a cool haven to read and access the internet -- several teenagers were playing WoW on the library computers, and I too am tapping into the resource. A possibly adrift artsy-type man of about my age similarly came to conduct his wayward business, having 'just ended up in Springfield', saying it as both and excuse and a badge of pride evincing his free spirit.

The woman is one of the classic types of hypochondriac, and though I'm only listening to them the EMT and police men know this, but they also know that on the off chance of being wrong, not taking the situation seriously could be a disaster. And so they administered simple blood pressure and pulse rate tests, both which seemed normal, then went about convincing her that she needed to be taken to the hospital to be completely checked out, thereby shifting the burden of liability to a place better protected by the standard operating procedure of a battery of tests.

The woman immediately protested, worried about the heavy cost of a ambulance ride, coupled with a paranoia that she would lose her walker. To this the EMT -- a short woman with her practical ponytail shoved through a baseball cap, as often they do -- let glints of irritation show through, asking her repeatedly to decide which hospital she wished to go to, and then asking her to arrange another means to the hospital. The woman protested, but the EMT could scarecly be blamed -- she is stuck in a system not of her design -- and somehow the smooth-souled librarian, who before had been placating library customers by putting holds on books, convinced both parties to go to the nearest hopsital. How exactly this was done I'll forever remain in ignorance, for another ambulance spun through the downtown circle at that instant, scattering sports cars, stopping sedans, and causing the skaters to pause their idling and look.

The incident vaguely reminds me when I had similar issues in Brooklyn, when i was sufficiently pained to drive my ass through the dirty orange-lit streets to a hospital in Williamsburg. They proceeded to do drug tests on me, despite my insistences, but everything checked out fine. In retrospect, the pain was likely heartburn antagonized by psychological isolation; this was before I really learned to listen to myself, and take care of the social and more basic physiological needs. The walker woman fell through these same cracks in a likely preventable but now very expensive way.

Meanwhile, a large black transsexual and a wrinkly white guy walk hurriedly past the plate glass windows of the library, talking animatedly. They may be in a fissure of sorts, but i doubt they consider it a fall...

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ref: -0 tags: loops feedback arcs video game programming date: 04-30-2012 15:12 gmt revision:0 [head]

I highly agree with this philosophy / this deconstruction of the flow of information in human structures: http://www.lostgarden.com/2012/04/loops-and-arcs.html

On criticism as a meta-arc game:

"In the past I've discussed criticism as a game that attempts to revisit an arc repeatedly and embellish it with additional meaning. The game is to generate essays superficially based on some piece of existing art. In turn, other players generate additional essays based off the first essays. This acts as both a referee mechanism and judge. Score is accumulated via reference counts and by rising through an organization hierarchy. It is a deliciously political game of wit that is both impenetrable to outsiders and nearly independent of the actual source arcs. Here creating an arc becomes a move in the larger game. "

{1158}
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ref: -0 tags: bees energy harvesting honey date: 04-11-2012 06:02 gmt revision:2 [1] [0] [head]

This morning hundreds of bees were swarming outside my front door -- a fact is not without reason, as my roommate makes honey, and her hive just today outgrew the apiary. Hence the hive split this morning, and one queen be left to wait on a branch outside while scouts searched for good places to build a new colony; meanwhile hundreds of non-scout workers were swarming around her.

Bees are amazing. Anyway, a friend sent a link to an article describing how to generate microwatts of energy off a flying insect, which led me to wonder how much energy those bees could have been producing instead of milling protectively about their queen.

  • number of bees : 1000
  • power, with direct connection to flight muscles: 400 uW
  • total possible power: 400mW
  • kCal in a tablespoon (21g) of honey: 64
    • in joules: 270kJ
  • Length of time it would take for 500 madly flapping bees (1) to generate the energy within a tablespoon of honey: 375 hours (15.6 days)
  • Yield of honey from a large, productive hive: 150 lbs / year (2)
    • in watts: 27.8 W
    • number of bees: 20000 (2)
    • factor better than energy harvesting: 3.5

Conclusion: let them make honey :-)


(1) Half the bees visible were resting on leaves, not madly flapping.

(2) Rough wiki-google estimate.

{1157}
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ref: -0 tags: spike sorting variational bayes PCA Japan date: 04-04-2012 20:16 gmt revision:1 [0] [head]

PMID-22448159 Spike sorting of heterogeneous neuron types by multimodality-weighted PCA and explicit robust variational Bayes.

  • Cutting edge windowing-then-sorting method.
  • projection multimodality-weighted principal component analysis (mPCA, novel).
    • Multimodality of a feature is by checking the informativeness using the KS test of a given feature.
  • Also investigate graph laplacian features (GLF), which projects high-dimensional data onto a low-dimensional space while preserving topological structure.
  • Clustering based on variational Bayes for Student's T mixture model (SVB).
    • Does not rely on MAP inference and works reliably over difficult-to sort data, e.g. bursting neurons and sparsely firing neurons.
  • Wavelet preprocessing improves spike separation.
  • open-source, available at http://etos.sourceforge.net/

{1156}
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ref: -0 tags: Hutchison oscillations basal ganglia beta gamma globus pallidus date: 03-26-2012 16:21 gmt revision:2 [1] [0] [head]

PMID-15496658 Neuronal oscillations in the basal ganglia and movement disorders: evidence from whole animal and human recordings.

  • This is a review / mini-symposium (only 3 pages)
    • Cites other Hutchison papers: 1997, 1998.
  • Critique classical hypothesis in that GPi firing does not increase that much, 10-22% in animal models. IT explains akinesia and bradykinesia, but not rigidity or tremor. (This was 8 years ago, remember!)
    • Plus, most neurons have intrinsic pacemaker-like properties that sets the rate of firing in the absence of synaptic input. (Bevan et al 2002).
  • Oscillations:
    • Alpha band enhanced after MPTP treatment in green monkeys and in the STN of some PD patients with tremor at rest.
    • Higher frequency oscillations (beta, 15-25Hz) can be observed in some patients without resting tremor.
    • Much slower oscillations discovered by Judith Walters, 6 OHDA rat (0.3 - 2Hz).
    • Also ultralow, multisecond oscillations, which appear in dopamine stimulated rats. (Ruskin et al 1999a,,b, 2003).
      • Lesion of the STN was not found to change these ultralow oscillations, but did modify the connectivity between GP and SNr.
    • Courtemanche et al 2003 studied the possible normal physiological function for oscillations in basal ganglia networks.
      • Beta band decreased during saccadic eye movements.
      • LFP syncronization showed task-related decrease, but only in sites engaged in the task, as evicenced by saccade-related activity.
  • Boraud tested gradual small-dose administration of MPTP toxin:
    • Minimal changes in the average firing rate of GPi neurons
    • Oscillatory activity between 4-9 and 11-14 Hz, with differences between monkeys.
      • Oscillations increased with symptom presentation.
  • Goldberg et al 2004: analyzed coherence between EEG and BG LFP; surmise that in the PD condition the basal ganglia and cortex become more closely entrained by global brain dynamics, which are reflected in the widespread local field potentials.
  • Peter Brown: oscillations in the beta band are enhanced to such an extent in Parkinson's disease that voluntary movements are not generated because motor command for initiation cannot override the enhanced oscillatory state.
    • That is, movement initiation corresponds to beta-band desynchronization, and movement command cannot 'break through'.

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ref: Hashimoto-2003.03 tags: cortex striatum learning carmena costa basal ganglia date: 03-07-2012 23:18 gmt revision:3 [2] [1] [0] [head]

PMID-22388818 Corticostriatal plasticity is necessary for learning intentional neuroprosthetic skills.

  • Trained a mouse to control an auditory cursor, as in Kipke's task {99}. Did not cite that paper, claimed it was 'novel'. oops.
  • Summed neuronal firing rate of groups of 2 or 4 M1 neurons.
    • One grou increased the frequenxy with increased firing rate; the other decreased tone with increasing FR.
  • Removal of striatal NMDA receptors impairs the ability to learn neuroprosthetic skills.
    • Hence, they argue, cortico-striatal plastciity is required to learn abstract skills, such as this tone to firing rate target acquisition task.
  • Auditory feedback was essential for operant learning.
  • Controlled by recording EMG of the vibrissae + injection of lidocane into the whisker pad.
  • One reward was sucrose solution; the other was a food pellet. When the rat was satiated on one modality, they showed increased preference for the opposite reward. Clever control.
  • Noticed pronounced oscillatory spike coupling, the coherence of which was increased in low-frequency bands in late learning relative to early learning (figure 3).
  • Genetic manipulations: knockin line that expresses Cre recombinase in both striatonigral and striatopallidal medium spiny neurons, crossed with mice carrying a floxed allele of the NMDAR1 gene.
    • These animals are relatively normal, and can learn to perform rapid sequential movements, but are unable to learn precise motor sequences.
    • Acute pharmacological blockade of NMDAR did not affect performance of the neuroprosthetic skill.
    • HEnce the deficits in the transgenic mice are due to an inability to perform the skill.

{1151}
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ref: -0 tags: meng poon wireless power transfer date: 03-07-2012 22:23 gmt revision:0 [head]

IEEE-4353634 (pdf) Optimal Operating Frequency in Wireless Power Transmission for Implantable Devices

{696}
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ref: Jarosiewicz-2008.12 tags: Schwartz BMI learning perturbation date: 03-07-2012 17:11 gmt revision:2 [1] [0] [head]

PMID-19047633[0] Functional network reorganization during learning in a brain-computer interface paradigm.

  • quote: For example, the tuning functions of neurons in the motor cortex can change when monkeys adapt to perturbations that interfere with the execution (5–7) or visual feedback (8–10) of their movements. Check these refs - have to be good!
  • point out that only the BMI lets you see how the changes reflect changes in behavior.
  • BMI also allows pertubactions to target a subset of neurons. apparently, they had the same idea as me.
  • used the PV algorithm. yeck.
  • perturbed a select subset of neurons by rotating their tuning by 90deg. about the Z-axis. pre - perturb - washout series of experiments.
  • 3D BMI, center-out task, 8 targets at the corners of a cube.
  • looked for the following strategies for compensating to the perturbation:
    • re-aiming: to compensate for the deflected trajectory, aim at a rotated target.
    • re-waiting: decrease the strength of the rotated neurons.
    • re-mapping: use the new units based on their rotated tuning.
  • modulation depths for the rotated neurons did in fact decrease.
  • PD for the neurons that were perturbed rotated more than the control neurons.
  • rotated neurons contributed to error parallel to perturbation, unrotated compensated for this, and contributed to 'errors' in the opposite direction.
  • typical recording sessions of 3 hours - thus, the adaptation had to proceed quickly and only online. pre-perturb-washout each had about 8 * 20 trials.
  • interesting conjecture: "Another possibility is that these neurons solve the “credit-assignment problem” described in the artificial intelligence literature (25–26). By using a form of Hebbian learning (27), each neuron could reduce its contribution to error independently of other neurons via noise-driven synaptic updating rules (28–30). "
    • ref 25: Minsky - 1961;
    • ref 26: Cohen PR, Feigenbaum EA (1982) The Handbook of Artificial Intelligence; 27 references Hebb driectly - 1949 ;
    • ref 28: ALOPEX {695} ;
    • ref 29: PMID-1903542[1] A more biologically plausible learning rule for neural networks.
    • ref 30: PMID-17652414[2] Model of birdsong learning based on gradient estimation by dynamic perturbation of neural conductances. Fiete IR, Fee MS, Seung HS.

____References____

[0] Jarosiewicz B, Chase SM, Fraser GW, Velliste M, Kass RE, Schwartz AB, Functional network reorganization during learning in a brain-computer interface paradigm.Proc Natl Acad Sci U S A 105:49, 19486-91 (2008 Dec 9)
[1] Mazzoni P, Andersen RA, Jordan MI, A more biologically plausible learning rule for neural networks.Proc Natl Acad Sci U S A 88:10, 4433-7 (1991 May 15)
[2] Fiete IR, Fee MS, Seung HS, Model of birdsong learning based on gradient estimation by dynamic perturbation of neural conductances.J Neurophysiol 98:4, 2038-57 (2007 Oct)

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ref: -0 tags: implicit motor sequence learning basal ganglia parkinson's disease date: 03-06-2012 22:47 gmt revision:2 [1] [0] [head]

PMID-19744484 What can man do without basal ganglia motor output? The effect of combined unilateral subthalamotomy and pallidotomy in a patient with Parkinson's disease.

  • Unilateral lesion of both STN and GPi in one patient. Hence, the patient was his own control.
    • DRastically reduced the need for medication, indicating that it had a profound effect on BG output.
  • Arm contralateral lesion showed faster reaction times and normal movement speeds; ipsilateral arm parkinsonian.
  • Implicit sequence learning in a task was absent.
  • In a go / no-go task when the percent of no-go trials increased, the RT speriority of contralateral hand was lost.
  • " THe risk of persistent dyskinesias need not be viewed as a contraindication to subthalamotomy in PD patients since they can be eliminated if necessary by a subsequent pallidotomy without producting deficits that impair daily life.
  • Subthalamotomy incurs persistent hemiballismus / chorea in 8% of patients; in many others chorea spontaneously disappears.
    • This can be treated by a subsequent pallidotomy.
  • Patient had Parkinsonian symptoms largely restricted to right side.
  • Measured TMS ability to stimulate motor cortex -- which appears to be a common treatment. STN / GPi lesion appears to have limited effect on motor cortex exitability 9other things redulate it?).
  • conclusion: interrupting BG output removes such abnormal signaling and allows the motor system to operate more normally.
    • Bath DA presumably calms hyperactive SNr neurons.
    • Yuo cannot distrupt output of the BG with compete imuntiy; the associated abnormalities may be too subtle to be detected in normal behaviors, explaniing the overall clinical improbement seen in PD patients after surgery and the scarcity fo clinical manifestations in people with focal BG lesions (Bhatia and Marsden, 1994; Marsden and Obeso 1994).
      • Our results support the prediction that surgical lesions of the BG in PD would be associated with inflexibility or reduced capability for motor learning. (Marsden and Obeso, 1994).
  • It is better to dispense with faulty BG output than to have a faulty one.

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ref: bookmark-0 tags: basal ganglia dopamine reinforcement learning Graybeil date: 03-06-2012 18:14 gmt revision:4 [3] [2] [1] [0] [head]

PMID-16271465 The basal ganglia: learning new tricks and loving it

  • BG analogous to the anterior forebrain pathway (AFP), which is necessary for song learning in young birds. Requires lots of practice and feedback. Studies suggest e.g. that neural activity in the AFP is correlated with song variability, and that the AFP can adjust ongoing activity in effector motor pathways.
    • LMAN = presumed homolog of cortex that receives basal ganglia outflow. Blockade of outflow from LMAN to RA creates stereotyped singing.
  • To see accurately what is happening, it's necessary to record simultaneously, or in close temporal contiguity, striatal and cortical neurons during learning.
    • Pasupathy and biller showed that changes occur in the striatum than cortex during learning.
  • She cites lots of papers -- there has been a good bit of work on this, and the theories are coming together. I should be careful not to dismiss or negatively weight things.
  • Person and Perkel [48] reports that in songbirds, the analogous GPi to thalamus pathway induces IPSPs as well as rebound spikes with highly selective timing.
  • Reference Levenesque and Parent PMID-16087877 who find elaborate column-like arrays of striatonigral terminations in the SNr, not in the dopamine-containing SNpc.

{1018}
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ref: Rouse-2011.06 tags: BMI chronic DBS bidirectional stimulator Washington Medtronic ASIC translational date: 03-05-2012 23:56 gmt revision:3 [2] [1] [0] [head]

PMID-21543839[0] A chronic generalized bi-directional brain-machine interface.

  • Using a commercial neurostimulator package & battery etc.
  • "A key goal of this research prototype is to help broaden the clinical scope and acceptance of NI techniques, particularly real-time brain state detection" Good purpose! good work!
  • Augments the stimulator with 4 channels of ECoG/LFP + accelerometer + wireless telemetry.
    • Can be used to detect parkinsons state or pre-epileptiform behavior.
      • Much of this has been though of before, it just took the technology to catch up & a group to make it.
    • Chronic data is needed from humans -- animal models are often inadequate.
  • Tested in a primate for brain control of a cursor: 1D control using ECoG.
    • Good Left/right ROC, actually.
    • A large cost is simply the clinical testing; hence they piggy-back on an existing design.
    • There should be more research-industry collaborations like this.
  • impressive specs.
  • SVM classification algorithm (only consumed 10uW!) for data compression.
  • short-time Fourier transform for extracting the power over a given band. This using a modified chopper-amplification scheme. Output data has a bandwidth of less than 5Hz, which greatly reduces processing requirements.
  • Lots of processing on the BASIC chip, much like here.
  • Also see the press release

____References____

[0] Rouse AG, Stanslaski SR, Cong P, Jensen RM, Afshar P, Ullestad D, Gupta R, Molnar GF, Moran DW, Denison TJ, A chronic generalized bi-directional brain-machine interface.J Neural Eng 8:3, 036018 (2011 Jun)

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ref: Mink-1996.11 tags: basal ganglia review parkinsons STN DBS date: 03-05-2012 23:33 gmt revision:13 [12] [11] [10] [9] [8] [7] [head]

PMID-9004351[0] The basal ganglia: focused selection and inhibition of competing motor programs.

  • Plenty of focus on diseased states, but normal function is unclear.
  • basal ganglia do not generate motor programs; that is the task of the cerebrum / cerebellum (based on timing).
  • review posits that the inhibitory output of the BG acts to seletively inhibit competing motor mechanisms in order to prevent them from interfering with voluntary movements that are generated by other CNS structures.
  • Involvement of the BG in motor control old -- dates back to Kinner Wilson describes pathology of rigidity and tremor following lenticular degeneration.
    • Thought that the pyramidal system was new and plastic, whereas the extrapyramidal system was archaic and postural / static.
    • Extrapyramidal system is actually prepyramidal, too.
  • Striatum.
    • receives excitatory input from all of the cerebrum except primary auditory and visual cortices.
    • cortical projections terminate in longitudinal bands.
    • in reciprocally connected areas of frontal, temporal, and parietal cortex terminate in adjacent or interdigitating zones in the striatum.
    • somatotopy in projections: areas receiving input from the face area of sensory or motor cortex are separate from those receiving input from the arm area.
    • The zones themselves overlap / are interdigitated, but not completely.
    • 95% of the cells are medium spiny neurons (MSN).
      • The remainder are glutamine from centromedian and parafasicular nuclei of the thalamus, cholinergic input from large aspiny neurons, GABA from neighboring MSTs, and dopamine from SNpc.
    • When Flaherty and Graybiel (1994) PMID-7507981[1] injected retrograde tracer into GPi and anterograde tracer into sensory or motor cortex they were able to demonstrate multiple striatal zones that were labeled from both injections. This suggests that information is sent from cortex to striatum in a multiply convergent and divergent pattern with reconvergence in GPi after processing in the striatum (Fig. 2).
    • Caudate projects to SNpc
    • Putamen projects to the GPi.
    • Acetylcholine: there is a patchy distribution of heavily and lightly stained regions, corresponding to striosomes and the matrix.
      • Dendrites of most MSN are restricted to a single compartment.
      • both striosomes and matrix receive input from the SNpc, but only the striosomes project back to the SNpc.
      • Striosomes can affect the matrix via large aspiny neurons, AChe, 1-2% of the total striatal population.
    • One striatal cell receives input from thousands of cortical cells.
      • Activation of a MSN appears to require concurrent excitatory input from a large number of cortical afferents.
    • MSNs have a low resting firing rate of 0.1 - 1 Hz -- strong resting potassium current.
      • Cells can switch between two stable states: hyperpolarized -80mV and moderately polarized -50mV.
      • This appears to be stabilized by large aspiny cholinergic neurons (?)
  • D1 increases cAMP, D2 usually decreases cAMP. both expressed on MSN; some suggest differentially, based on anatomical target.
  • STN
    • dendrites up to 1200um.
    • in GPi and SNpr, STN axon collaterals branch to ensheath the cell bodies and proximal dendrites of their target neurons.
    • each axon from the subthalamic nucleus ensheathes many GPi neurons.
    • Input primarily from the oculo-and somato-motor areas of the frontal lobes.
    • does not seem to have much intrinisic processing; it's more of a relay.
  • GPi:
    • About 70% send axon collaterals to both thalamus and brainstem.
    • Projects to ventrolateral (Vlo) and ventral anterior nucleus (VApc).
    • Little overlap in projections fom the basal ganglia and the cerebellum in the thalamus.
    • collaterals of most GPi axons projecting to thalamus project to an area at the junction of the midbrain and pons adjacent to the pedunculopontine nucleus (PPN). Some call it the "midbrain extrapyramical area", which projects to the reticulospinal motor system.
  • GPe:
    • Most output inhibitory to STN; most input from the striatum and STN.
    • Also output to GPi and SNr.

Electrophysiology:

  • In the striatum, cells fire in relation to both the direction of movement (25%) as well as the direction of force (50%) (Crutcher and DeLong 1984b PMID-6705862[2]).
  • More cells fire during slow "ramp" movements than during fast "ballistic" movements, possibly due to their relation to proximal muscle activity, or due to force / speed modulation.
  • Cells fire phasically relative to cue, to movement, or after movement / before the next movement ("set" neurons). .
  • In the putamen, most activity is late, though there is a distribution anterior-posterior, with anterior cells more likely to fire early; these are possibly of cognitive origin.
  • In the striatum, activity has been found to context-dependent: e.g. cells respond to touch, but only if it is within the context of a movement.
    • Romo et. a.l 1992 controlled for this wrt externally triggered movements vs. self-initiated movements.
    • Within the caudate, Hikosaka et al 1989a described cell firing in the caudate relative to delayed, cued, and remembered saccades.
      • context-dependent activity is a feature of the striatum, but not necessarily the function.
  • Cholinergic large aspiny neurons appear to have no relation to movement.
    • But they do fire in relation to sensory input or to reward.
    • Since one effect of cholinergic input to MSN is to stabilize the present state, in the situation where the current behavior results in a reward, activity of the cholinergic interneurons would tend to reinforce the ongoing pattern of striatal activity. Interesting!! memory!

STN:

  • tonically active, with a resting rate of 20 Hz.
  • somatotopic organization, lower extremity dorsal and face / eyes ventral.
  • neurons increase firing rate in relation to eye or limb movement. (Matsumura et al 1992, Wichmann et al 1994a [3]).
  • In monkeys treained to perform elbow movements, 60-75% STN neurons had activity related to movement direction (Georgopoulos et al 1983) (Wichmann et al 1994a).
    • Unclear proportion responded to passive movement: 20% former, 50% latter.
  • It is not known to what degree STN neurons discharge in relation to other movement parameters. Only 1 study, with only 7 neurons, had some correlation to velocity ( Georgopoulos 1983)
  • Onset of activity slower than M1 or EMG.
  • Ventral STN: of all task-related neurons, 23% were related to saccades, 39% related to visual fixation, 15% to visual sensory responses.
  • Matsumura 1992 shows that 52% of STN neurons had activity related to maintained eye position but not to saccades.
    • STN supresses saccades: STN excites SNr which inhibits collicular neurons involved in saccade generation.
  • in MPTP monkeys, ablation or inactivation of the STN cauyses transient diskinesia but when it resolved monkeys were able to move normally. (BErgman et al 1990; Wichmann et al 1994b).

GPi:

  • activity does not correlate with physical parameters of movement.
    • no consistent relationship between GPi activity and joint position, force production, movement amplitude, or movement velocity during wrist movement.
    • little correlation of GPi output with EMG profiles either.
  • Ramp and ballistic movements: equal amounts of control.

SNr:

  • All involved in eye movements are tonically active.
  • virtually all have been reported to decrease activity during eye movement.
    • Still yet: SNr show firing rate decreases while GPi show firing rate increases.
    • Decreased SNr discharge results in disinhibition in the superior colliculus to initiate saccades.
    • Could also be that the SC generates simultaneous eye and head movements, and the SNr helps to inhibit (?) neck muscles.
  • None in response to saccades in the dark (!)
  • Over half have sensory responses.

GPe:

  • 2 types
    • HF, 70 Hz, interrupted with long pauses.
    • LF, 10 Hz, with frequent spontaneous bursts.
  • Activity during movement remarkably similar to GPi.
  • Weak encoding of movement amplitude, velocity, and muscle length and force is weak.
    • Movement related activity is late.
  • Might effect center - surround inhibition on the GPi; unclear what it does to the STN?

SNpc:

  • Schultz and Romo 1995 - SNpc neurons respond as early as possible to stimuli that indicates the availability of reward, and to the presence of reward, but only within a context.
    • No tuning to movement.

Synthesis:

  • Author believes that the basal ganglia serve to repress motor actions / plans that compete with the present or desired movement.
    • Eg. ones that are elicited through auto-association in the cerebral cortex.
    • corrolary: if there is an inability to focally inhibit competing mechanisms generally, it might be expected that the resulting movement deficit would be compounded during a sequence of movements, as is observed.
  • Discrete lesions in experimental animals often do not produce the movement disorders associated with human basal ganglia disease.
  • If the tonically active basal ganglia output inhibits competing motor mechanisms, the tonic inhibition must be removed from desired mechanisms. This must be done in a focused manner at the right time and in the right context in order not to activate competing mechanisms. The vast machinery of the striatum with its context-specificity, plasticity and spatiotemporal filtering selects which MPGs should be allowed to turn on. Thus, when a movement is made, the basal ganglia output has two parallel actions: inhibition of a multitude of competing MPGs via STN and GPi and focused selection of desired MPGs via striatum and GPi. Dysfunction of either of these actions would cause abnormal posture and movement.

Parkinson's disease:

  • Symptoms:
    • Tremor at rest
    • bradykinesia
    • paucity of movement (akinesia)
    • muscular rigidity
    • abnormally flexed posture with postural instability.
  • Tremor possibly from abnormal bursting in the thalamus. (Pare et al 1990)
  • Highly idiopathic and progressive.
  • Symptoms may reflect involvement of other systems in addition to the nigrostriatal dopamine system.
  • Bradykinesia:
    • excessive co-contraction, insufficient agonist activity.
    • movement is more impaired when visual cues are absent.
      • self-initiated movements are slower than visually cued movements
      • more impaired when deprived of visual feedback of the ongoing movement or if they cannot see the moving body.
      • Likely they have an increased dependence on visual feedback to compansate for the deficit.
    • slower on simultaneous and sequential movements than they were on individual components (Benecke et al 1986, 1987).
      • Greater latency to begin second movement.
      • Others have found no particular sequencing deficit (Agostino et al 1994).
  • Rigidity likely due to inability to inhibit reflex mechanisms.
    • One of these is the transcortical reflex, which can (normally) be inhibited when subjects are instructed not to resist movement.
      • PD patients have abnormally increased transcortical stretch reflexes.
      • Reflex cannot be inhibited upon instruction (Berardelli et al 1983, Rothwell et al 1983, Taton and Lee 1975).
    • When normal subjects are subjected to a perturbation in the anterior-posterior dimension while standing, they have a stereotyped pattern of muscle activity in the legs and trunk that maintains upright stance. If they then sit down and are subjected to the same perturbation, this activity no longer occurs. By contrast, patients with Parkinson’s disease have an inappropriate cocontraction of leg and back muscles in response to perturbation from upright stance. When the same subjects are subjected to a perturbation in a sitting position, they continue to have the same pattern of muscle activity. (Horak et al 1992)
  • Akinesia
    • May be due to a loss of of dopamine input to the prefrontal, premotor, or motor cortex. (Gaspar et al 1991, 1992; Sawaguchi and Goldman-Rakic 1994).
      • Animals with focal lesions to dopamine input to prefrontal cortex have prolonged reaction times (Humer et al 1994); animals with basal ganglia lesion do not.
  • Microwriting / micrographia: common problem where writing size is normal initially, but within several letters the writing gets progressively smaller so that by the end of the line, it may be illegible.
    • Hypothesis: depending on the movement and mechanisms involved, the number of mechanisms competing with the desired movement may increase additively as the sequence progresses leafing to progressive slowing of the movement.

Huntingtons

  • Early stages characterized by frequent, brief, random twitch-like movements and dementia. smoe of the movements resemble normal voluntary movement.
  • Involuntary EMG bursts 50 - 300 ms in duration.
  • Marked loss of striatal neurons.
    • Specifically, MSN enkephalin-containing that project to GPe. (Reiner 1988).
    • Substance-P MSN that project to GPi and SNr are preserved until later in the disease when rigidity typically appears.
    • Experimental lesions in the striatum rarely cause chorea, which makes sense as it is the specific pattern of striatal cell loss that matters (Crossman, 1987).
    • Stroke of the striatum in humans rarely causes chorea.
  • It should be emphasized that neurons in many parts of the brain including cortex and cerebellum degenerate in Huntington's disease, hence inferences of basal ganglia function drawn from HD must be interpreted with caution.
  • In contrast to PD, the long-latency stretch reflex is absent or reduced in Huntington's disease.
    • Plus somatosensory evoked potentials are markedly reduced.
    • People with chorea not from Huntington's disease have normal long-latency reflexes.

STN / Hemiballismus

  • Damage to STN by ischemic stroke results in bizarre involuntary movement that is charaterized by large amplitude, flinging (ballistic) movement of the contralateral extremities.
    • Symptoms are immediate and improve over time.
    • Similar to chorea, but more commonly affects proximal joints, and the movements are larger.
  • Hemiballismus can be caused by injecting biculculine into STN, which is somewhat paradoxical since biculculine is a GABA antagonist and would be expected to cause disinihbition (activation) of STN. Yet the results are similar to lesion of STN. (Crossman 1987)
  • After STN lesion there is decreased activity in GPe and GPi.
  • Hemiballismus can be eliminated by lesioning GPi outputs (Carpener 1950).
  • STN is exitatory in GPi / GPe; lesioning reduces GPi's ability to inhibit competing motor programs.
    • Loss of excitatory input to GPi results in abnormal phasic or bursting activity in GPi or its targets and this bursting causes twitches or chorea.

Experimental lesions:

  • Focal inactivation of the putamen with GABA-A agonist muscimol causes decreased movement amplitude with cocontraction of agonist and antagonist muscles in visually-guided arm movements.
  • Lesions studies suggest that the striatum is functionally heterogeneous with the function of each component determined by its cortical afferents.
    • Authors suggest that the function of each component is more likely to be reflected in its outputs than inputs.
  • Caudate does seem involved in more cognitive processing; it has different connectivity despite similar construction.
  • Muscimol into the SNr results in involuntary saccades and inability to mantain fixation.
    • Thus, just as GPi inactivation results in abnormal excess limb and trunk muscle activity, SNr inactivation results in abnormal excess eye movements. (Hikosaka and Wurtz, 1985b).
  • Lesion of GPi is an old treatment for PD in humans (Cooper and Bravo, 1958). \
    • Surprisingly, the most consistent beneficial effect of pallidotomy may be the reduction of dyskinesias that are induced by L-Dopa treatment (Laitinen et al 1992).

Large papers are not dissimilar from large software projects -- they take time, iteration, and concentration. Papers, however, are harder as the feedback is not immediate and gratifying.

____References____

[0] Mink JW, The basal ganglia: focused selection and inhibition of competing motor programs.Prog Neurobiol 50:4, 381-425 (1996 Nov)
[1] Flaherty AW, Graybiel AM, Input-output organization of the sensorimotor striatum in the squirrel monkey.J Neurosci 14:2, 599-610 (1994 Feb)
[2] Crutcher MD, DeLong MR, Single cell studies of the primate putamen. II. Relations to direction of movement and pattern of muscular activity.Exp Brain Res 53:2, 244-58 (1984)
[3] Wichmann T, Bergman H, DeLong MR, The primate subthalamic nucleus. I. Functional properties in intact animals.J Neurophysiol 72:2, 494-506 (1994 Aug)

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ref: -0 tags: delong georgoupolos basal ganglia DBS date: 03-05-2012 22:04 gmt revision:2 [1] [0] [head]

PMID-6389041 Functional organization of the basal ganglia: contributions of single-cell recording studies.

  • CAn't seem to find the paper ... these observations are from the abstract.
  • phasic changes in neural discharge in relation to movements of specific body parts (e.g. leg, arm, neck, face);
  • short-latency (sensory) neural responses to passive joint rotation;
  • a somatotopic organization of movement-related neurons in GPe, GPi, and STN;
  • a clustering of functionally similar neurons in the putamen and globus pallidus;
  • greater representation of the proximal than of the distal portion of the limb;
  • changes in neural activity in reaction-time tasks, suggesting a greater role of the basal ganglia in the execution than in the initiation of movement in this paradigm; a clear relation of neuronal activity to direction, amplitude (?velocity) of movement, and force;
  • a preferential relation of neural activity to the direction of movement, rather than to the pattern of muscular activity.
  • suggest that the basal ganglia may play a role in the control of movement parameters rather than (or independent of) the pattern of muscular activity.
  • The presence of somatotopic organization in the putamen and globus pallidus, together with known topographic striopallidal connections, suggests that segregated, parallel cortico-subcortical loops subserve 'motor' and 'complex' functions.

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ref: -0 tags: Albin basal ganglia dopamine 1989 parkinsons huntingtons hemiballismus date: 03-02-2012 00:28 gmt revision:1 [0] [head]

PMID-2479133 The functional anatomy of basal ganglia disorders.

  • Matrix neurons mainly containing substance P mainly project upon the GPi or SNr
    • while those containing enkephalins project on the GPe.
  • Striosome neurons projecting to the SNc contain mainly substance P.
  • Classical hypothesis:
  • Hyperkinetic disorders, which are characterized by an excess of abnormal movements, are postulated to result from the selective impairment of striatal neurons projecting to the lateral globus pallidus.
    • These are suppressed by D2 receptor antagonists & exacerbated by dopamine agonists.
    • Chorea is a primary example.
    • Despite Huntingtons, traumatic, ischemic, or ablative lesions of the striatum in man or animals rarely produces chorea or atheosis (writhing movements).
    • In HD, cholinergic agonists will alleviate choreoatheosis, while anti-cholinergic drugs exacerbate it.
  • Hypokinetic disorders, such as Parkinson's disease, are hypothesized to result from a complex series of changes in the activity of striatal projection neuron subpopulations resulting in an increase in basal ganglia output.
    • opposite of HD, exacerbated by D2 antagonists and ameliorated by DA agonists, as well as anti-cholinergics.
  • Dystonia = the spontaneous assumption of unusual fixed postures lasting from seconds to minutes.

  • Standard model suggests that striatal lesions should result in spontaneous movements, while this is not the case in man or other mammals. (less inhibition on GPi / SNr -> greater susceptibility of the thalamus to competing programs (?))
  • hyperkinetic movements can be produced by infusing bicululline, a GABA receptor antagonist, into GPe -- silencing it.
  • In early HD, when chorea is most prominent, there is a selective loss of striatal neurons projecting to the LGP (enkephalin staining).
    • Substance P containing neurons are lost later in the disease.
  • Administration of D2 antagonists increases the synthesis of enkephalins and pre-proenkephalin mRNA in the striatum.
    • This presumably represents increases in neuronal activity.
    • Inhibition of GPe neurons decreases hyperkinetic movements? But STN is excitatory? This does not add up.
  • Hemiballismus may be caused by disinhibition of SNr (?) and the VA/VL/MD/CM-Pf thalamocortical projections.

Saccades:

  • In both PD and HD, there are both increases in the latency of initiation of saccades, slowing of saccadic velocity, and interruption of saccades.
    • In HD, there is an early loss of substance-P containing striatal terminals in the SNr, possibly resulting in over-inhibition of tectal neurons.
    • HD patients cannot supress saccades to flashed stimulus.
    • No abnormalities in saccadic control in tourette's syndrome.
  • Hikosaka: suggest that caudate neurons involved in the initiation of saccades are part of a mechanism in which sensory data are evaluated in the context of learned behaviors and anticipated actions, and then used to initiate behavior.

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ref: Prescott-2006.01 tags: basal_ganglia action selection motor control robot date: 03-01-2012 17:56 gmt revision:4 [3] [2] [1] [0] [head]

PMID-16153803[0] The robot basal ganglia: action selection by an embedded model of the basal ganglia

  • they implemented a model of the basal ganglia in a robot. The model switches between competing (hypothetical) actions based on input salience. There are only a possible actions in their robot.
  • they reiterate the common conception that the basal ganglia are implicated in action selection: what to do next ( also mentioned are other functions - perception and cognition working memory and many other aspects of motor function. )
  • huh, interesting : cognitive psychologists have discovered that when an observable system has more than three interacting parts, it becomes very difficult for human minds to predict accurately how that system will change over time. (!!!) I dig disclaimers like this.
    • therefore, very limited understanding can be gleaned from informal, box and arrow style models.
      • I think the same is true of many biological analysis - including analysis of the immune and nervous systems - it needs to be at a much higher level of quantification
    • they also say that a model must be validated by placing it within the entire behavioral system.
  • the basal ganglia seem to be suitable for switching between competing channels & providing the required clean selection of a winner.
    • (1) striatal cells have up and down states, and can only switch between them with heavy coincident inputs.
    • (2) selective local inhibition between channels.
    • (3) dopamine innervation D1 = exitation; D2 = inhibition. I never really got how this enters their model; figure 1 seems like it would describe it, but it needs more math :)
    • (4) feedforward off-center, on surround network. they ref some other work..
      • I still don't feel like their explanation is the best (they use kinda wishy-washy terms) - though it is a step in the right direction.
  • people with schizophrenia sometimes switch cognitive focus rapidly; schizo is though to be due to a dopamine imbalance. Same problem with ADD.
    • treatment for ADD: amphetamine (blocks monoamine transporter, increases extracellular concentration of DA), ritalin. Both allow for heightened concentration: once you select a task, you stick with 'it' (the thought / prediction pathway) for longer. Dopamine is definintely involved in action selection, duhh.
    • their model supports this behavior: If the tonic dopamine level is very low, the robot has difficulty initiating actions; if the DA level is high, then it tends to select more than one action at the same time. (wait.. this implies that DA is too high in people with ADD? what? perhaps this is a consequence of the two different types of DA receptors? )
  • (...) basal ganglia - thalamo-cotrical loops my act to provide a positive feedback pathway that can maintain appropriate level of salience to selected behavior.
  • much of the input to the basal ganglia comprises collateral fibers from motor regions that project to the spinal cord and brainstem structures.
    • activity changes in the BG occur slightly after the beginning of EMG activity (good evidence!) Such signals may be important for controlling the maintenance and termination of selected behavior.

My thoughts:

  • what if the STN is involved in controlling the stability of neuronal activity - that is, preventing motor feedback instability by knocking down the gain. (whereas the cerebellum is involved in the balance and coordination interpretations of stability)
    • Normally, the human motor system is very stable, but when you lack dopamine innervation, you both cannot move (become very rigid) & have tremor (an inability to control cyclical oscillations).
      • That is, perhaps oscillation is due to a intrinsic inability to modulate gain.
      • more likely it is a manifestation/symptom of pathological activity in the control loop.

____References____

[0] Prescott TJ, Montes González FM, Gurney K, Humphries MD, Redgrave P, A robot model of the basal ganglia: behavior and intrinsic processing.Neural Netw 19:1, 31-61 (2006 Jan)

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ref: Litvak-2011.02 tags: DBS MEG STN synchrony oscillations london connectivity beta basal ganglia date: 02-29-2012 19:59 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

PMID-21147836[0] Resting oscillatory cortico-subthalamic connectivity in patients with Parkinson’s disease

  • Used MEG plus LFP recordings of the STN.
  • Two spatially and spectrally separated networks were identified.
    • A temporoparietal-brainstem network was coherent with the subthalamic nucleus in the alpha (7-13 Hz) band,
    • whilst a predominantly frontal network was coherent in the beta (15-35 Hz) band.
  • Dopaminergic medication modulated the resting beta network, by increasing beta coherence between the subthalamic region and prefrontal cortex.
  • Idea of characterizing connectivity based on synchronization / comodulation: (Fries 2005).
  • Synchronization is exaggerated in Parkinson's disease (Sharott et al 2005b, Mallet et al 2008).
  • Some patients had dopamine dysregulation syndrome and medication-induced hypersexuality.
  • None of the > 45 Hz STN LFP patterns had a scalp pattern consistent with a cortical source.
  • Cortical source frequency not really that different between ON and OFF medication, except at maybe tremor frequencies.
  • But cortex drives the subthalamic area robustly.
    • That said, these patients were at rest.
    • Small difference between ON and OFF states possibly because they were at rest.
  • Both healthy subjects and those with parkinson's disease show resting connectivity between basal ganglia and the SMA, temporopareital area and parts of the prefrontal cortex. (Postuma and Dagher 2006); Helmich et al 2010).
  • Beta band coupling between cerebral cortex and subthalamic nucleus drops before and during movement (Cassidy et al 2002 PMID-12023312; Lalo et al 2008)
    • During imagination of movement (Kuhn et al 2008).
    • During action observation (Alegre et al 2010).
      • Is this consistent with the conflict / reinforcement learning hypothesis?
  • A big problem is determining if the oscillations are pathological or non-pathological
    • Impossible to control, since we cannot record from healthy humans.

____References____

[0] Litvak V, Jha A, Eusebio A, Oostenveld R, Foltynie T, Limousin P, Zrinzo L, Hariz MI, Friston K, Brown P, Resting oscillatory cortico-subthalamic connectivity in patients with Parkinson's disease.Brain 134:Pt 2, 359-74 (2011 Feb)

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ref: -0 tags: bilateral STN lesion rats perseverence nose poke impulsivity DBS basal ganglia date: 02-29-2012 17:44 gmt revision:1 [0] [head]

PMID-9421169 Bilateral lesions of the subthalamic nucleus induce multiple deficits in an attentional task in rats.

  • Excitotoxic lesion of STN alleviate motor impairment found in PD dopamine depletion model.
  • What about normal rats?
  • investigated the behavioural effects of bilateral excitotoxic lesions of the STN in rats performing a five-choice test of divided and sustained visual attention, modelled on the human continuous performance task.
  • This task required the animals to detect a brief visual stimulus presented in one of five possible locations and respond by a nose-poke in this illuminated hole within a fixed delay, for food reinforcement
  • STN lesion:
    • decreased discriminatory activity
    • increase premature responses & preservative panel pushes and nose-poke responses.
  • Subsequent D1/D2 anatagonist administration reduced premature responses but not preservative nose-pokes.
  • Consistent with action selection and inhibition.
  • Suggest that these cognitive-type effects should be examined in humand that have STN DBS.

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ref: Timmermann-2003.01 tags: DBS double tremor oscillations DICS beamforming parkinsons date: 02-29-2012 00:39 gmt revision:4 [3] [2] [1] [0] [head]

PMID-12477707[0] The cerebral oscillatory network of parkinsonian resting tremor.

  • Patients had idiopathic unliateral tremor-dominated PD.
  • MEG + EMG -> coherence analysis. (+ DICS for deep MEG recording).
  • M1 correlated to EMG at tremor and double-tremor frequency following medication withdrawal overnight.
    • M1 leads by 15 - 25 ms, consistent with conduction delay.
  • Unlike other studies, they find that many cortical areas are also coherent / oscillating with M1, including:
    • Cingulate and supplementary motor area (CMA / SMA)
    • Lateral premotor cortex (PM).
    • SII
    • Posterior pareital cortex PPC
    • contralateral cerebellum - strongest at double frequency.
  • In contrast, the cerebellum, SMA/CMA and PM show little evidence for direct coupling with the peripheral EMG but seem to be connected with the periphery via other cerebral areas (e.g. M1)
  • Power spectral analysis of activity in all central areas indicated the strongest frequency coherence at double tremor frequency.
    • Especially cerebro-cerebro coupling.
  • These open-ended observation studies are useful!

____References____

[0] Timmermann L, Gross J, Dirks M, Volkmann J, Freund HJ, Schnitzler A, The cerebral oscillatory network of parkinsonian resting tremor.Brain 126:Pt 1, 199-212 (2003 Jan)

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ref: -0 tags: dopamine reinforcement learning funneling reduction basal ganglia striatum DBS date: 02-28-2012 01:29 gmt revision:2 [1] [0] [head]

PMID-15242667 Anatomical funneling, sparse connectivity and redundancy reduction in the neural networks of the basal ganglia

  • Major attributes of the BG:
    • Numerical reduction in the number of neurons across layers of the 'feed forward' (wrong!) network,
    • lateral inhibitory connections within the layers
    • modulatory effects of dopamine and acetylcholine.
  • Stochastic decision making task in monkeys.
  • Dopamine and ACh deliver different messages. DA much more specific.
  • Output nuclei of BG show uncorrelated activity.
    • THey see this as a means of compression -- more likely it is a training signal.
  • Striatum:
    • each striatal projection neuron receives 5300 cortico-striatal synapses; the dendritic fields of same contains 4e5 axons.
    • Say that a typical striatal neuron is spherical (?).
    • Striatal dendritic tree is very dense, whereas pallidal dendritic tree is sparse, with 4 main and 13 tips.
    • A striatal axon provides 240 synapses in the pallidum and makes 10 contacts with one pallidal neuron on average.
  • I don't necessarily disagree with the information-compression hypothesis, but I don't disagree either.
    • Learning seems a more likely hypothesis; could be that we fail to see many effects due to the transient nature of the signals, but I cannot do a thorough literature search on this.

PMID-15233923 Coincident but distinct messages of midbrain dopamine and striatal tonically active neurons.

  • Same task as above.
  • both ACh (putatively, TANs in this study) and DA neurons respond to reward related events.
  • dopamine neurons' response reflects mismatch between expectation and outcome in the positive domain
  • TANs are invariant to reward predictability.
  • TANs are synchronized; most DA neurons are not.
  • Striatum displays the densest staining in the CNS for dopamine (Lavoie et al 1989) and ACh (Holt et al 1997)
    • Depression of striatal acetylcholine can be used to treat PD (Pisani et al 2003).
    • Might be a DA/ ACh balance problem (Barbeau 1962).
  • Deficit of either DA or ACh has been shown to disrupt reward-related learning processes. (Kitabatake et al 2003, Matsumoto 1999, Knowlton et al 1996).
  • Upon reward, dopaminergic neurons increase firing rate, whereas ACh neurons pause.
  • Primates show overshoot -- for a probabalistic relative reward, they saturate anything above 0.8 probability to 1. Rats and pigeons do not show this effect (figure 2 F).

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ref: Wichmann-1994.08 tags: STN normal physiology delong wichmann date: 02-27-2012 22:05 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-7983514[0] The Primate Subthalamic Nucleus. 1. Functional Properties in Intact Animals.

  • Lots of cells -- 301 cells in the STN, 1589 microstimulation sites, 72 cross-correlation pairs.
  • 55% modulated to passive contralateral movement, 86% of these to muscle palpitation, 25% to light touch.
  • Caudalventral STN devoid of calls responding to touch or movement.
  • Somatotopic organization: lateral arm, medial leg.
    • Representation of proximal muscles / portions much larger than distal portions, consistent with Carpenter 1950.
  • Mostly rate increases in response to step tracking tasks, usually uniphasic.
  • 40ua, 200-500 ms train duration, 400 Hz did not produce movement. Stimulation of the lateral borders often led to eye movements.
  • 11% of pairs were seen to be synchronized, separated by 100-200um.
    • Much smaller than in the cortex.
    • This strongly supports the concept of functional segregation in the basal ganglia-thalamocortical pathways.
  • Mean firing rate 23 Hz old studies, 19 Hz present study.
  • "Most hypotheses concerning the role of the basal ganglia in movement were derived from experience with diseases originating in the basal ganglia or from experiments involving the activation or inactivation of large parts of BG nuclei. These results are notoriously hard to interpret, because gross changes in motor circuit activity likely results in rather nonspecific activity changes in multiple parts of the neuraxis, unlike minute alterations in the firing patterns of individual neurons in the basal ganglia may have under physiological conditions".
  • Basal ganglia may have a role in the late phases of movement, perhaps even their termination.
  • "More is known about the role of the indirect pathway in the pathophysiology of movement disorders such as Parkinson's disease and ballism than in the control of normal movement." word, yes.

____References____

[0] Wichmann T, Bergman H, DeLong MR, The primate subthalamic nucleus. I. Functional properties in intact animals.J Neurophysiol 72:2, 494-506 (1994 Aug)

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ref: -0 tags: parent collateralization basal ganglia date: 02-24-2012 22:00 gmt revision:0 [head]

PMID-11052216 Organization of the basal ganglia: the importance of axonal collateralization.

  • "...revealed the presence of various types of projection neurons with profusely collateralized axons within each of the major components of the basal ganglia. Such findings call for a reappraisal of current concepts of the anatomical and functional organization of the basal ganglia, which play such a crucial role in the control of motor behavior. "

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ref: DeLong-1985.02 tags: globus pallidus subthalamic STN electrophysiology Georgopoulos DeLong DBS date: 02-24-2012 21:50 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-3981228[0] Primate globus pallidus and subthalamic nucleus: functional organization

  • cells respond to arm, leg, and orofacial movements (mostly in the arm tho)
  • ~25% of these responded to passive joint movement - the latency is in accord with proprioceptive driving.
  • arm-related neurons were found throughout the rostrocaudal extent of both globus pallidus segments
  • look @ the articles that cite this!

____References____

[0] DeLong MR, Crutcher MD, Georgopoulos AP, Primate globus pallidus and subthalamic nucleus: functional organization.J Neurophysiol 53:2, 530-43 (1985 Feb)

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ref: -0 tags: globus pallidus delong response tuning date: 02-24-2012 21:41 gmt revision:1 [0] [head]

PMID-4997823 Activity of Pallidal Neurons During Movement

  • GPe activity notably different from GPi.
    • "So characteristic were the discharge patterns of units in each segment that early in the course of the experiment ti be came apparent when the electrode entered and left each segment.
  • Two types of cells in GPe:
    • High frequency with periods of quiet (85%)
    • Low frequency with bursts.
  • Only one type in GPi: continuous HF discharge, 10-100 Hz, mean 63 Hz.
  • Mostly contralateral, ~ 15% ipsilateral related discharge.
  • Leg and arm responding units intermixed.
  • Conclusion: pallidus not involved in reflexes.
  • Substantia innominata = region posterior the pallidus, contains the nucleus basalis.
  • I'd really like to get recordings of this quality!

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ref: -0 tags: putamen functional organization basal ganglia date: 02-24-2012 21:01 gmt revision:0 [head]

PMID-6705861 Single cell studies of the primate putamen. I. Functional organization.

  • Cells in the striatum have very low levels of activity -- some are simply not spontaneously active.
  • Other cells are tonically active at 3-6Hz (cholinergic?)
  • ( Most cells related to the direction of movement, not necessarily force.
  • Two types of load reactions: short latency (presumably sensory) and long-latency (motor -- related to the active return movement of the arm.)
  • Timing suggests that the striatum does not play a role in the earliest phases of movement, consistent with cooling studies, kainic acid lesions, or microstimulation. Only 19% of neurons were active before movement.
  • Many neurons were reactive to both active and passive movements in the same joint / direction.
    • The BG receive afferents from joint and not muscle receptors.

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ref: -0 tags: Romo basal ganglia movement control date: 02-24-2012 19:50 gmt revision:2 [1] [0] [head]

PMID-1483512 Role of the primate basal ganglia and frontal cortex in the internal generation of movements. I. Preparatory activity in the anterior striatum

  • Recorded from the head of the audate and rostral putamen.
  • Both spontaneous and cued / delayed-reward tasks.
  • Observed responses:
    • transient responses to cue, (2x as many to 'go' as 'nogo' cues)
    • sustained activity preceding the trigger stimulus or movement onset
      • Often this was ramp-like, indicating some sort of preparatory activity.
      • This could last 2-35 seconds, depending on the task, with a maximum of 80 s.
  • Premovement activity began 0.5-5.0s before movement onset (median 1 second).
    • Unrelated to saccadic eye movements.
    • 2/3 of these neurons were active only in spontaneous movements, and not in cued movements.
    • This is similar to activity in the frontal cortex; hence both are involved in preparing actions.

PMID-1483513 Role of primate basal ganglia and frontal cortex in the internal generation of movements. II. Movement-related activity in the anterior striatum.

  • Same experiments and recordings as above.
  • Time-locked responses to trigger, 60ms latency, independent of modality.
  • 44 neurons increased their activity before earlier EMG
  • 55 were activated with the movement,
  • 50 neurons were activated after movement onset.
  • I'm not entirely sure how this is different from above. (?)

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ref: 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: Bergman-1998.01 tags: basal ganglia globus pallidus electrophysiology parkinsons 2001 DBS date: 02-22-2012 18:52 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-9464684[0] Physiological aspects of information processing in the basal ganglia of normal and parkinsonian primates.

  • The firing of neurons in the globus pallidus of normal monkeys is almost always uncorrelated.
  • after MPTP treatment, the firing patterns of GP became correlated and oscillatory (see the figures!!)
  • dopamine must support normal segregation of the informational channels in the basal ganglia, and breakdown of this causes the pathology of PD.
  • has a decent diagram of the basal ganglia-thalamo-cortical circuits.
  • two different hypotheses of BG function: segregated and convergent. data support the former.

____References____

[0] Bergman H, Feingold A, Nini A, Raz A, Slovin H, Abeles M, Vaadia E, Physiological aspects of information processing in the basal ganglia of normal and parkinsonian primates.Trends Neurosci 21:1, 32-8 (1998 Jan)

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ref: RodriguezOroz-2001.09 tags: STN SNr parkinsons disease single unit recording spain 2001 tremor oscillations DBS somatotopy organization date: 02-22-2012 18:24 gmt revision:12 [11] [10] [9] [8] [7] [6] [head]

PMID-11522580[0] The subthalamic nucleus in Parkinson's disease: somatotopic organization and physiological characteristics

  • Looks like they discovered exactly what we have discovered ... only in 2001. This is both good and bad.
    • From the abstract: "Neurones responding to movement were of the irregular or tonic type, and were found in the dorsolateral region of the STN. Neurones with oscillatory and low frequency activity did not respond to movement and were in the ventral one-third of the nucleus. Thirty-eight tremor-related neurones were recorded."
  • Again, from the abstract: "The findings of this study indicate that the somatotopic arrangement and electrophysiological features of the STN in Parkinson's disease patients are similar to those found in monkeys."
  • It may be that we want to test differential modulation / oscillation: look for differences between rest and activity, if there is sufficient support for both these in the files we have.
  • These people were much, much more careful about localization of their single-electrode tracks. E.g. they calculated electrode location relative the DBS electrode stereotatically, and referenced this to the postoperative MRI location of the treatment electrode.
  • Many more (32% of 350 neurons) responded to active or passive movement.
  • Of this same set, 15% (31 neurons) had a firing rate with rhythmical activity; 38 neurons had rhythmic activity associated with oscillatory EMG, but most of these were responsive to passive stimulation.
  • Autocorrelation of the neuronal bursting and tremor peaked at mean 7Hz, while autocorr. of EMG peaked at mean 5Hz.
  • This whole paragraph is highly interesting: ''The neuronal response associated with active movements was studied by simultaneous recording of neuronal EMG activity of the limbs. Five tremor-related neurons, recorded while a voluntary movement was performed, were available for analysis. Voluntary activation of a particular limb segment arrested the tremor. This was associated with a change in the discharges of the recorded neuron, which fired at a slower rate and in synchrony with the voluntary movement. On occasions, freezing of the voluntary movement ensued and tremor reappeared, changing the neuronal activity back to the typical 4-5Hz tremor-related activity. The cross-correlation analysis of two such neurons showed a peak frequency of 4.63 and 4.88 Hz for tremor-related activity, and 1.5 to 1.38 Hz during voluntary movement. Whether neuronal discharges in the STN preceded or followed EMG activity of the limbs could not be precisely established under the present conditions.
  • Somatotopic representation in the STN is expected from normal and MTPT-treated monkeys. Indeed, somatotopy is enhanced int he GPm of MTPT-treated monkeys.
    • This somatotopy is likely to result from organized afferent from the primary motor cortex (M1) to dorsolateral STN; this is the target of DBS treatment. Ventral and medial STN seems to project to associative and limbic cortical regions.
    • It seems they think the STN is generally not diseased, it is just a useful target for stimulating without evoked movement as in M1. This is consistent with optogenetic studies by Deisseroth [1].
    • Supporting this: "DBS of STN in Parkinson's disease improves executive motor functions, but aggravates conditional associative learning.
  • Interesting: In Parkinson's disease patients with tremor, Levy and colleagues found synchronization and a high firing rate (>10Hz) while recording pairs of neurons >600um apart.
  • Recordings of cortical activity through EEG and STN LFP showed significant coherence in the beta and gamma frequency bands during movement - consistent with corticosubthalamic motor projection. ... and suggest that the STN neurons involved in parkinsonian tremor are the same as the ones ativated during the performance of a voluntary movement. (! -- I agree with this.)
  • More: The reciprocal inhibitory-excitatory connections tightly linking the GPe and the STN may generate self-perpetuating oscillations.

Old notes:

  • this paper concentrates on STN electrophysiology in PD.
    • has a rather excellent list of references.
  • found a somatotopic organization in the STN, with most motor-related units more irregular and in the dorsolateral STN.
  • found a substantial fraction of tremor-synchronized neurons.
  • conclude that the somatotopic organization is about the same as in monkeys (?) (!)
  • M1 projects to STN, as verified through anterograde tracing studies. [1] These neurons increase their firing rate in response to passive movements.
  • there appears to be a relatively-complete representation of the body in the dorsolateral STN.

____References____

[0] Rodriguez-Oroz MC, Rodriguez M, Guridi J, Mewes K, Chockkman V, Vitek J, DeLong MR, Obeso JA, The subthalamic nucleus in Parkinson's disease: somatotopic organization and physiological characteristics.Brain 124:Pt 9, 1777-90 (2001 Sep)
[1] Gradinaru V, Mogri M, Thompson KR, Henderson JM, Deisseroth K, Optical deconstruction of parkinsonian neural circuitry.Science 324:5925, 354-9 (2009 Apr 17)

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ref: Heimer-2006.01 tags: STN DBS synchrony basal ganglia reinforcement learning beta date: 02-22-2012 17:07 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

PMID-17017503[0] Synchronizing activity of basal ganglia and pathophysiology of Parkinson's disease.

  • They worry that increased synchrony may be an epi-phenomena of tremor or independent oscillations with similar frequency.
  • Modeling using actor/critic models of the BG.
  • Dopamine depletion, as in PD, resultis in correlated pallidal activity, and reduced information capacity.
  • Other studies have found that DBS desynchronizes activity -- [1] or [2].
  • Biochemical and metabolic studies show that GPe activity does not change in Parkinsonism.
  • Pallidal neurons in normal monkeys do not show correlated discharge (Raz et al 2000, Bar-Gad et al 2003a).
  • Reinforcement driven dimensionality reduction (RDDR) (Bar-Gad et al 2003b).
  • DA activity, through action on D1 and D2 receptors on the 2 different types of MSN, affects the temporal difference learning scheme in which DA represents the difference between expectation and reality.
    • These neurons have a static 5-10 Hz firing rate, which can be modulated up or down. (Morris et al 2004).
  • "The model suggests that the chronic dopamine depletion in the striatum of PD patients is perceived as encoding a continuous state where reality is worse than predictions." Interesting theory.
    • Alternately, abnormal DA replacement leads to random organization of the cortico-striatal network, eventually leading to dyskinesia.
  • Recent human studies have found oscillatory neuronal correlation only in tremulous patients and raised the hypothesis that increased neuronal synchronization in parkinsonism is an epi-phenomenon of the tremor of independent oscillators with the same frequency (Levy et al 2000).
    • Hum. might be.
  • In rhesus and green monkey PD models, a major fraction of the primate pallidal cells develop both oscillatory and non-oscillatory pair-wise correlation
  • Our theoretical analysis of coherence functions revealed that small changes between oscillation frequencies results in non-significant coherence in recording sessions longer than 10 minutes.
  • Their theory: current DBS methods overcome this probably by imposing a null spatio-temporal firing in the basal ganglia enabling the thalamo-cortical circuits to ignore and compensate for the problematic BG".

____References____

[0] Heimer G, Rivlin M, Israel Z, Bergman H, Synchronizing activity of basal ganglia and pathophysiology of Parkinson's disease.J Neural Transm Suppl no Volume :70, 17-20 (2006)
[1] Kühn AA, Williams D, Kupsch A, Limousin P, Hariz M, Schneider GH, Yarrow K, Brown P, Event-related beta desynchronization in human subthalamic nucleus correlates with motor performance.Brain 127:Pt 4, 735-46 (2004 Apr)
[2] Goldberg JA, Boraud T, Maraton S, Haber SN, Vaadia E, Bergman H, Enhanced synchrony among primary motor cortex neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine primate model of Parkinson's disease.J Neurosci 22:11, 4639-53 (2002 Jun 1)

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ref: Wichmann-2011.12 tags: DBS STN basal ganglia bursts oscillation review wichmann beta date: 02-22-2012 17:05 gmt revision:13 [12] [11] [10] [9] [8] [7] [head]

PMID-21723919[0] Pathological basal ganglia activity in movement disorders.

  • The paradigm has shifted: initial idea was that firing rates changed,
  • later in detailed description of basal ganglia firing rate changes:
    • burst patterns and oscillations
  • 6-OHDA murines + MPTP monkey models so essential yada yada.
  • intraoperative microelectrode recordings yada yada.
  • Nice figure:
    • Black = inhibitory; gray = excitatory. From Galvan and Wichmann 2008.
    • note differences between D2 and D1.
  • Recall corticostriatal fibers are often (50%) collaterals from corticospinal axons.
  • Corticostriatal pathway separate from cortico-subthalamic pathway, so the two get different signals. (Parent and Parent 2006).
    • Few collaterals, and of those axons go to red nucleus and cerebral peduncle -- not pyramids.
  • Indirect (GPe, STN targets) and direct (GPi/SNr) striatal projections generally, but not completely, seem separate.
  • VA = ventroanterior; VL = ventrolateral thalamus.
  • Collaterals from GPi/SNr reach the intralaminar thalamic nuclei: the CM (centromedian) and the PF (parafascicular) nuclei.
  • One of the important additional function of the intralaminar thalamic nuclei is to provide saliency information to the striatum during procedural learning (Kimura et al 2004; Minamimoto et al 2009).
  • There is a considerable body of evidence that the absence of dopaminergic transmission may trigger changes in the density and morphology of dendritic spines on striatal projection neurons.
    • Thereby influencing corticostriatal transmission.
    • This is consistent with the progressive nature of the disease.
  • Serotonin and acetylcholine also involved in striatum, but their role in PD less well characterized.
  • Tremor and dystonia possibly due to afferents from the deep cerebellar nuclei and efferents to the cerebellar cortex.
  • Rate model failures:
    • thalamotomy procedures did not result in worsening of parkinsonism.
    • GPi lesions produced bradykinesia in normal monkeys (despite the GABA output!)
    • GPe lesions do not produce parkinsonism.
    • not all studies report changes in FR in GPi/GPe.
    • A significant factor interfering with the assessment of FR changes in PD patients is that its dependent on the state of arousal of the patients.
  • Burstiness: Increased burstiness (Fig. 2A) has emerged as one of the most reliable abnormalities of neuronal firing in the basal ganglia in parkinsonism, as shown in dopamine-depleted monkeys and in patients with PD
  • Oscillations: much in the beta band (10-35 Hz) throughout extrastriatal BG.
old redirect: see [1]
  • LFP power:
  • Brown is the purveyor of the high kinetic / low akinetic hypothesis (2003, 2005).
  • Oscillations do not occur in acute dopamine depletion.
  • GABA receptor blockade in GPe results in dyskinesias.
  • STN inactivation results in ballismus, as noted elsewhere.
  • GPi lesioning is clinically used to abolish dyskinesias in patients with treatment-resistant hyperkinetic movements.

____References____

[0] Wichmann T, Dostrovsky JO, Pathological basal ganglia activity in movement disorders.Neuroscience 198no Issue 232-44 (2011 Dec 15)
[1] Rodriguez-Oroz MC, Rodriguez M, Guridi J, Mewes K, Chockkman V, Vitek J, DeLong MR, Obeso JA, The subthalamic nucleus in Parkinson's disease: somatotopic organization and physiological characteristics.Brain 124:Pt 9, 1777-90 (2001 Sep)

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ref: Parent-1995.01 tags: basal ganglia anatomy review STN GPe DBS date: 02-22-2012 15:48 gmt revision:17 [16] [15] [14] [13] [12] [11] [head]

PMID-7711769[0] Functional anatomy of the basal ganglia. I. The cortico-basal ganglia-thalamo-cortical loop.

  • Pallidal and nigral neurons have wide dendritic arborizations at right angles to the unbranched incoming striatal axons, leading to (hypothetically) a confulence of information from distinct functional striatal territories on many neurons and to extreme reception convergence [242].
    • This pattern suggests that projections arising from very small areas of the cortex may extend through very large regions of the striatum, particularly along the rostrocaudal plane.
    • Individual striatal neurons receive relatively few synapses from restricted cortical areas; this makes it difficult to conceive how the cortico-striatal projection system could convey information in a highly specific manner; specificity does not exist at a cellular level.
  • Cortex to striatum:
    • Virtually all cortical functional areas contribute, at varying degrees, to the cortico-striatal projection, inputs from the sensorimotor cortex being particularly extensive and those from the visual cortex much less so.
    • Cortico-sriatal projection originates from neurons located in both supragranular (layers I-III) and infragranular (V,VI) cortical layers.
    • Cortical neurons project ipsilaterally or contralaterally, but not usually bilaterally.
    • Cortical cells arborize on restricted, topologically defined domains in the striatum.
    • Restricted cortical regions project to parasagitally elongated domains in the caudate nucleus.
      • this seems to be a general feature. see B and C below.
      • Reminds me of the cerebellum.
    • non-adjacent cortical areas (prefrontal and pareital cortices)project to adjacent striatal territories.
    • The association, sensorimotor, and limbic cortical areas project in a segregated manner onto threes distinct striatal regions referred to as the associative, sensorimotor, and limbic striatal territories.
    • In this view, cortical information is not directly transposed at striatal level, but is integrated and transformed into strict associative, sensorimotor, and limbic functional modalities.
  • Convergence and divergence:
    • There is a vast reduction in the number of neurons from the cortex to the striatum.
    • This has led many to infer overlap or convergence.
    • Actual projection is patchy -- divisions of striosomes and extrastriosomal matrix -- with the individual axons sending out further sub-patches.
      • This degree of segregation breaks down for sensorimotor territory.
    • cortico-striatal neurons in infragranular layers project principally to striosomes while those in supragranular layers send their axons to the matrix. things are tightly organized.
  • The output cells of the matrix are grouped in clusters in relation to the different projection systems that lead from the striatum to the GPe and GPi. These are called 'matrisomes'.
    • These might be a way of bringing into proximity different cortical signals so they can be recombined in novel ways.
    • That said, there was substantial topographical overlap of the frontal eye field and the supplementary eye field, and though these are closely interdigitated they do not mix.
  • Medium spiny neurons:
    • The primary projection neurons of the striatum.
    • GABA. Plus substance P, enkephalin, dynorphin and neurotensin. (!)
      • The coexistence of GABA with a given peptide in a spiny neuron is in correlation with it's target site.
      • At that time they didn't know what the peptides did.
    • Axon emits several collaterals:
      • Local axonal arborizations restricted tot he dendritic domain of its cell of origin or a nearby cell -- inluding an 'autonapse' or of nearby projection neurons.
      • Less common axonal arborization goes far beyond and often does not overlap the dendritic domain of the cell of origin.
    • Projected to by the cortex, thalamus, and the SNc.
    • Usually silent, except with cortical / thalamic input.
  • Interneurons in the striatum are non-spiny.
    • Less than 2% (of entire striatal population, not just interneurons) them are huge, cholinergic cells.
      • These form symmetric synapses on virtually all parts of MSN.
    • Medium, 1% of population, have short axons and are GABA ergic.
    • Second medium, nitrous oxide signaling interneurons.
    • SNc efferents synapes ontot the base of the spines, but only on MSN that have cortical afferents.
    • Thalamic input synapse onto morphologically distinct type of MSN.
    • Destruction of the dopaminergic nicgro-striatal pathway results in a decrease in levels of mRNA for substance P and increase in mRNA for enkephalin.
  • Striatal MSN projections:
    • Relatively discrete in cats and monkeys; highly collateralized in rats, where many neurons project to GPe, GPi, SN, or some pair.
  • Fibers from the associative territory massively invade the whole extent of SNr, without clear territorial demarcation.
    • Meanwhile, inputs from the limbic striatal territory appears to be widely distributed in the substantia nigra & VTA.
  • Most authors think that the distinction between the GPi and SNr is artificial -- they are split by the internal capsule.
    • However, GPi is mostly sensorimotor, while SNr is associative.
  • Projections from striatum to pallidus * SNr very organized and layered.
    • Pictures. read the paper. words do not do this justice.
    • For example, injections of anterograde tracers in various sectors of the striatum produce elongated, longitudinally oriented terminal fields that cover nearly the entire rostrocaudal extent of the substantia nigra.
    • "The dorsal climbing fibers and the corresponding wooly fibers from replicable modular units whose boundaries do not respect the limit between SNc and SNr compartments. ... They are distrinuted along the rostrocaudal extent of the substantia nigra according to a remarkably precise and constant sequence.
  • As in [1]: striatal and subthalamic terminals converge onto the same pallidal neurons within these regions of overlap, possibly in register with those from the striatum.
    • The striato-pallidal fibers and striato-nigral fibers arborize at least twice in the target structures, suggesting there are multiple copies of the same information to distinct subsets of pallidal/nigral populations.
      • Meanwhile, GPi/SNr axons are highly collateralized and not strictly confined to disctinct subnuclei.
      • That is, output is both convergent and divergent.
      • There are several multi-laminar models of the SNr [54] or the globus pallidus [243].
  • Regarding information funneling due to the very large dendritic fields of pallidal neurons:
    • anterograde double-labeling experiments in the squirrel monkey clearly indicate that neighboring striatal cell populations do not have overlapping terminal fields in the GP or SN.
      • Axons from adjacent striatal cell populations produce two sets of terminal fields that interdigitate but never mix.
      • cortical information is conveyed and integrated along multiple, segregated channels.
  • Output of GPi/SNr = VA, VL thalamus, both ipsi and contralateral.
    • Lesser: pedunculopontine tegmental nucleus & centromedian thalamus, superior colliculus.
    • Highly collateralized output.
    • Lamellar distribution of cells that share similar functional characteristics.
    • Synapse almost exclusively on thalamic projection neurons.
    • Centromedian nucleus: no projection to the cortex; rather projects to the striatum, hence is involved in regulation.
    • Pedunculopontine nucleus: mostly re-afferent back to the BG!
      • innervation of the SNc, subthalamic nucleus, and the pallidum. [95,149,186-188,202,207,215,263,277].
      • Acetylcholine output.
      • Deep cerebellar nuclei project to the pedunculopontine nuclei in primates.
  • GPe: efferent fibers from large terminal boutons that make synapses mostly of the symmetrical type with proximal dendrites and soma of GPi/SNr neurons. These GABA synapses may be of ultimate importance in regulating activity.
    • Also projects to the reticulothalamic region, which supplies GABA synapses to the rest of the thalamus, hence GPe can disinhibit most of the thalamus. Such complexity.

____References____

[0] Parent A, Hazrati LN, Functional anatomy of the basal ganglia. I. The cortico-basal ganglia-thalamo-cortical loop.Brain Res Brain Res Rev 20:1, 91-127 (1995 Jan)
[1] Parent A, Hazrati LN, Functional anatomy of the basal ganglia. II. The place of subthalamic nucleus and external pallidum in basal ganglia circuitry.Brain Res Brain Res Rev 20:1, 128-54 (1995 Jan)

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ref: Shink-1996.07 tags: STN GPe GPi globus_pallidus anatomy retrograde tracing DBS date: 02-22-2012 15:34 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-8783253[0] The subthalamic nucleus and the external pallidum: two tightly interconnected structures that control the output of the basal ganglia in the monkey.

  • interconnected neurons in the subthalamic nucleus and the globus pallidus external innervate the same population of neurons in the internal segment of the globus pallidus.
    • e.g. there is a consistent functional organization between the three areas! (need to look up the organization of the striatum, too).
  • they did a similar study with injections of dextran amine into the GPi, and found that the labeled neurons in the STN and GPe were, as before, in register.
    • labeled GPe axons were not reactive to GABA & seemed to be from STN
    • labeled STN axons seemed to be from the GPe & were GABA reactive.
  • Has anyone traced out the connection in the brain of a Parkinson's patient? Does it change with the disease?

____References____

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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: Isoda-2008.07 tags: STN switching motor control scaccades monkeys electrophysiology DBS date: 02-22-2012 15:02 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-18614691[0] Role for subthalamic nucleus neurons in switching from automatic to controlled eye movement.

  • we found neurons that showed a phasic change in activity specifically before volitionally controlled saccades which were switched from automatic saccades
  • A majority of switch-related neurons were considered to inhibit no-longer-valid automatic processes, and the inhibition started early enough to enable the animal to switch.
  • We suggest that the STN mediates the control signal originated from the medial frontal cortex and implements the behavioral switching function using its connections with other basal ganglia nuclei and the superior colliculus.
  • neurons have a really high rate of spiking - what we observe in DBS surgeries.
  • nice. There may be alternate explanations, but this one is plausible.

____References____

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ref: Parent-1995.01 tags: basal ganglia anatomy review STN DBS date: 02-22-2012 14:40 gmt revision:15 [14] [13] [12] [11] [10] [9] [head]

PMID-7711765[0] Functional anatomy of the basal ganglia. II. The place of subthalamic nucleus and external pallidum in basal ganglia circuitry.

  • 5 'sideways control structures' :
    • subthalamic nucleus (glutamate) STN
    • pars compacta of the substantia nigra (dopamine) SNpc
    • centromedian / parafasicular thalamic complex (glutamate) CM/Pf
    • dorsal raphe nucleus (serotonin)
    • pedunculopontine tegmental nucleus. (glutamate and acetylcholine) PPN
  • STN exitatory on the GPi and SNr. Which are basically the same thing.
  • Largest target is the GPe, to which it is reciprocally connected.
  • STN lesions produce ballism, violent, involuntary, wild, flinging movements usually limited to the side of the body contralateral to the lesion. Symptoms gradually resolve.
  • STN densely packed with soma, dendrites, and long axons.
    • But no (or few) interneurons.
  • Projects to:
    • GPe & GPi, SN, striatum, cerebral cortex, substantia innominata, pedunculopontine tegmental nucleus and the mesencephalic and pontine reticular formation.
    • These projections are topologically organized. Lateral -> dorsal pallidium, medial -> ventral pallidium (GPv).
    • Projections are often collaterals to GPe, GPi, and SNr in rodents; in primates, subsytems are separate.
    • Dorsolateral STN = sensorimotor, ventromedial = 'association'
  • STN projections lie parallel to GP neurons, arranged in lamina along the rostral-caudal axis.
    • These, like in the striatum, are arranged perpendicular to the afferent fibers.
    • Subthalamic and striatal neurons converge upon the same pallidal neurons.
    • "Subthalamic axons arborize throughout large caudorostral portions of the pallidum and appear to influence in a rather uniform manner large subpopulations of pallidal neurons in both pallidal segments."
  • Above: gray cells = pallidal neurons.
    • Suggests that STN cells can excite a rather large / diffuse population of pallidal cells, whereas striatum exerts a more specific inhibitory action.
  • STN neurons project somewhat diffusely and less topographically to SNr, with 'patchy' regions, very similar to other striatal-nigral projections.
    • Still, 90% of synapses in SN are GABA-ergic, < 10% are glutamatergic, so afferents from STN is not too large.
  • electrophysiological studies in the rat have suggested that efferent projections of the subthalamic nucleus control the inhibition of movement by setting the physiological conditions of pallidal and nigral neurons to the appropriate level prior the arrival of striatal signals.
  • STN projection to striatum diffuse, weak, unbranched and 'en passant'.
  • Afferent projections:
    • direct projection from the cerebral cortex. Might be collaterals from the pyramidal tract.
      • In rodents: 40% from the prefrontal cortex, 15% from the ACC, 9% M1.
    • In primates: Mostly M1, somatotopic organization (page 9), monosynaptic.
      • also S1, somatotopic, respond to sensory stimuli.
      • Dorsolateral sector of the subthalamic nucleus appears to be more involved in skeletomotor behavior, whereas the ventromedial sector appears more concerned with occulomotor and associative aspects of behavior [107].
  • Electrical stimulation of the cortex results in the STN a short-latency EPSP (monosynaptic) followed by brief inhibition IPSP (from the GP), then further EPSP.
  • Electrical stimulation of the STN does not elicit movements; stimulation within microzones of the striatum does.
  • more is known about the role of STN in eye movements through the SNr than skeletal motor control.
    • Venrtomedial sector of STN receives afferents from the frontal eye fields & supplementary eye fields.
    • SNr is known to exert a tonic GABAergic inhibition on neurons in the superior colliculus.
      • Inibition is suppressed by transient GABA inhibition originating from the caudate nucleus (disinhibition).
    • STN, in comparison, seems to suppress eye movements through the SNr -- perhaps to maintain attention on an object of interest, under control of the cortex (FEF). .
      • CF {169} : activation of the STN drives SNr activity, which inhibits the superior colliculus, allowing maintainance of eye position on an object of interest.
  • GPe projects directly to the STN, GABAergic, strong on proximal dendrites (less soma /distal),
    • Collaterals to both the STN and SNr, and to the greater striatum and entopeduncular nucleus.
    • Strong inhibitory effect on STN firing which appears to be chronic:
      • STN firing should only be elicited by strongly coherent or synchronized arrival of information from multiple extrinsic sources.
    • Recall there are two negations through the Striatum (GABA) & GPe (GABA).
  • The hypothesis behind Huntington's disease & PD:
    • PD: pallido-subthalamic pathway activity is decreased, leading to an increase in excitatory activity of STN on BG output structures -> greater GPi /SNr GABA ergic activity -> greater rigidity.
    • Huntingtons: pallido-subthalamic activity increased (striatal neurons lost), decreased excitation of STN -> less GPi/SNr GABAergic activity on VA/VL.
      • "leaving thalamocortical neurons to respond undiscriminatingly to all sorts of inputs and hence to hyperkinesia". Makes sense.
    • Above, classical direct and indirect pathway.
  • Re direct / indirect pathway: the evidence to support this is weak; inputs from the GPe seem to spare the area containing subthalamic cells projecting to the GPi/SNr.
    • Another way: pallidal control of the subthalamic nucleus in primates is exerted principally upon cells projecting back to the GPe and not upon cells projecting to GPi/SNr.
  • Only the centromedian / parafasicular complex of the thalamus projects to the STN. Important -- it is also an output structure of the BG.
    • These might be collaterals of the thalamo-striatal projection system.
    • Projections are topographic.
    • Respects boundaries: centromedian projects to sensorimotor laterodorsal STN; parafasicular nucleus innervates the associative / limbic portion of this structure. The associative projection is much stronger than the sensorimotor.
    • Glutamate.
  • Direct projections from the SNc; STN projects back to the SNr.
    • Dopamine, excitatory; much more present in rats than primates.
    • Marked increase in metabolism following dopamine agonist treatments.
    • Both D1 and D2 present (at least in rats).
  • Direct projections from the pedunculopontine tegmental nucleus to the STN.
    • Cholinergic.
    • Reciprocal -- relays BG information to the brainstem and spinal cord. Locomotion? cardiovascular changes?
  • Dorsal rahpe nucleus
    • Serotonin, obvi.
  • GPe:
    • Originally thought to project to STN to mediate it's glutamate projections
    • now realized to have many outputs, including to the GPi/SNr.
    • Strong afferents to the reticular thalamic nucleus (with bunched arborizations), GPi/SNr ('massive arborizations'), STN, and less to striatum.
    • Fibers from a small striatal cell group arborize twice in each pallidal segments in a rostrocaudal sequence manner.
    • GPe projections to GPI/SNr cell-to-cell.
      • These two together implies that the two striatal terminal fields in the GPe would effect two rostrally located sets of GPI/SNr cells 1 & 2 that are distinct from those innervated by the striatum more caudally than GPi/SNR cells 3 & 4 (above).
  • In animals at rest, striatal neurons are quiet, whereas SNr and GPi are tonically active.

____References____

[0] Parent A, Hazrati LN, Functional anatomy of the basal ganglia. II. The place of subthalamic nucleus and external pallidum in basal ganglia circuitry.Brain Res Brain Res Rev 20:1, 128-54 (1995 Jan)

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ref: -0 tags: mesh silk conformal coating date: 02-21-2012 20:03 gmt revision:0 [head]

PMID-20400953 Dissolvable films of silk fibroin for ultrathin conformal bio-integrated electronics.

  • Mounting such devices on tissue and then allowing the silk to dissolve and resorb initiates a spontaneous, conformal wrapping process driven by capillary forces at the biotic/abiotic interface.
  • Specialized mesh designs and ultrathin forms for the electronics ensure minimal stresses on the tissue and highly conformal coverage, even for complex curvilinear surfaces, as confirmed by experimental and theoretical studies.
    • Wow! cool!
  • polyimide electrode substrates 2.5 - 7.5 um thick. Electrodes were made of anisotropic conductive film.

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ref: -0 tags: DBS basal ganglia paradoxical kinesis reaction time date: 02-21-2012 19:52 gmt revision:1 [0] [head]

PMID-16758482 "Paradoxical kinesis" is not a hallmark of Parkinson's disease but a general property of the motor system.

  • Paradoxical kinesis is the idea that PD patients will suddenly spring to movement when propted by an extreme situation.
  • "Results showed that external cues and urgent conditions decreased movement duration (Urgent External Cue < External Cue < Self Generated) and reaction time (Urgent External Cue < External Cue)"
  • Results indicate that there is no difference in speed or reaction time improvement between controls and PD patients; it is a general property of the motor system.

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ref: -0 tags: DBS basal ganglia date: 02-21-2012 00:36 gmt revision:2 [1] [0] [head]

PMID-20519543 Motor sequences and the basal ganglia: kinematics, not habits.

  • Trained a monkey to make learned and random movements, > 50,000 training trials.
  • Inactivated sensorimotor region of GPi with muscimol,
  • Which resulted in dysmetria and slowing of individual movements, but these impairments were virtually identical for overlearned and random sequences.
  • The fluid predictive execution of learned sequences and the animals tendency to reproduce the sequence pattern in random trials was preserved following GPi blockade.
  • There is rather substantial evidence that the basal ganglia is the storage and expression site for learned sequential skills (first paragraphy of introduction).
    • But! ablation of GPi has few deleterious motor effects (Green et al. 2002) (Bastian et al 2003),
    • And actually improves some aspects of motor sequencing in humans (Kimber et al 1999; Obeso et al 2009)
    • Lesions of the birds BG homolog has little impairment on learned birdsong.
  • Little difference between motor behavior pre ad post injection,
    • though slightly slower (reaction time and velocity) post-injection,
    • and slightly larger spatial error (shorter movements).
  • Injections did not interfere with animals ability to switch between random and overlearned blocks.
    • Muscimol did not interfere with the animal's penchant for continuing with learned sequence when the random sequence matched it.
  • Conclusion: the BG contributes to motor execution but not to the production or storage of well learned skills.
  • They need to disable the GPi in a learning experiment.

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ref: Turner-2010.12 tags: STN DBS basal ganglia motor learning vigor scaling review date: 02-16-2012 21:27 gmt revision:3 [2] [1] [0] [head]

PMID-20850966[0] Basal ganglia contributions to motor control: a vigorous tutor.

  • Using single-cell recording and inactivation protocols these studies provide consistent support for two hypotheses: the BG modulates movement performance ('vigor') according to motivational factors (i.e. context-specific cost/reward functions) and the BG contributes to motor learning.
  • Most BG associated clinical conditions involve some form of striatal dysfunction -- clincal sings occur when the prinicpal input nucleus of the BG network is affected.
    • Lesions of the output nuclei are typically subtle, consistent that pallidotomy is an effective treatment for PD and dystonia.
    • It is better to block BG output completely than pervert the normal operations of motor areas that receive BG output.
    • Pathological firing patters degrade the ability of thalamic neurons to transmit information reliably.
      • Bad BG activity may block cortico-thalamic-cortico communication.
      • Hence BG treatment does not reflect negative images of normal function.
  • Years of debate have been resolved by a confirmation that the direct and indirect pathways originate from biochamically distinct and morphologically disctinct types of projection neurons [97, 105].
    • Direct: D1; indirect = D2, GPe.
  • CMPf projects back to the striatuim.
  • Movement representation in the BG: ref [36]
  • Results of GPi inactivation:
    • RT are not lengthened. These results are not consistent with the idea that the BG contributes to the selection or initiation of movement.
    • GPi inactivation does not perturb on-line error correction process or the generation of discrete corrective submovements.
      • Rapid and-path corrections are preserved in PD.
      • Challenges the idea that the BG mediates on-line correction of motor error.
    • GPi inactivation does not affect the execution of overlearned or externally cued sequences of movements.
      • contradicts claims, based on neuroimaging and clinical evidence, that the BG is involved in the long term storage of overlearned motor sequences or the ability to string together successive motor acts.
    • GPi inactivation reduces movement velocity and acceleration.
      • Very consistent finding.
      • Mirrors the bradykinesia observed in PD.
      • Common side-effect of DBS of the GPi for dystonia.
    • GPI inactivation produces marked hypometria -- unsershooting of the desired movement extent.
      • Un accompanied by changes in movement linearity or directional accuracy.
  • Conclusion: impaired gain.
    • Movement: bradykinesia and hypometria
    • hand-writing: micrographia
    • speech: hyophonia [65].
    • There is a line of evidence suggesting that movement gain is controlled independently of movement direction.
    • Motor cost terms, which scale with velocity, may link and animals' previous experience with the cost/benefit contingencies of a task [75] to its current allocation of energy to meet the demands of a specific task.
      • This is consistent with monkey rapid fatiguing following BG lesion.
      • Schmidt et al [5] showed that patients with lilateral esions of the putamen or pallidum are able to control grip forces normally in response to explicit sensory instructions, but do not increase grip force spontaneously despite full understanding that higher forces will earn more money.
    • Sensory cuse and curgent conditions increase movement speed equally in healthy subjects and PD patients.
  • BG and learning:
    • role in dopamine-mediated learning is uncontroversial and supported by a vast literature [10,14,87].
    • Seems to be involved in reward-driven acquisition, but not long-term retention or recall of well-learned motor skills.
    • Single unit recording studies have demonstrated major changes in the BG of animals as they learn procedural tasks. [88-90]
      • Learning occurs earlier in the striatum than cortex [89,90].
    • One of the sequelae associated with pallidotomy is an impaired ability to learn new motor sequences [22 92] and arbitrary stimulus-response associations [93].
    • BG is the tutor, cortex is the storage.

____References____

[0] Turner RS, Desmurget M, Basal ganglia contributions to motor control: a vigorous tutor.Curr Opin Neurobiol 20:6, 704-16 (2010 Dec)

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ref: Teagarden-2007.03 tags: STN striatum operant conditioning behavior rats 2006 DBS date: 02-15-2012 03:36 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-17182916[0] Subthalamic and Striatal Neurons Concurrently Process Motor, Limbic, and Associative Information in Rats Performing an Operant Task

  • STN encodes behavioral events (reinforcement, nose poke, correct / incorrect trials). So does the striatum.
  • This study is rather nonspecific, but it makes sense that a conserved and well connected region is active during learning & general behavior.
    • That is, while the subthalamic nucleus is considered an output relay of the basal ganglia, more likely it operates in parallel to facilitate forms of learning; as such, responses are shown to rewards, cues, etc.

____References____

[0] Teagarden MA, Rebec GV, Subthalamic and striatal neurons concurrently process motor, limbic, and associative information in rats performing an operant task.J Neurophysiol 97:3, 2042-58 (2007 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: -0 tags: neural recording doubling Stevenson Kording date: 02-08-2012 04:28 gmt revision:0 [head]

PMID-21270781 How advances in neural recording affect data analysis

  • Number of channels recorded doubles every 7 years.
  • This extrapolated from the past 50 years of growth.

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ref: Nordhausen-1996.07 tags: Normann Utah array recording date: 02-06-2012 21:37 gmt revision:3 [2] [1] [0] [head]

PMID-8836553[0] Single unit recording capabilities of a 100 microelectrode array. Nordhausen CT, Maynard EM, Normann RA.

  • Used the Utah array in visual stimulus-evoked response in cats.
  • 58.6% of electrodes in the array recorded neural activity.
  • The density of the electrodes in the UIEA makes it impossible to simply push the needles into the cortex with forceps. This only results in surface dimpling, incomplete insertion, and possible cortical damage.
    • We have instead designed a high speed pneumatic insertion tool which takes advantage of viscoelectric properties of the cortical tissue by advancing the electrodes into the tissue at very high velocity.

____References____

[0] Nordhausen CT, Maynard EM, Normann RA, Single unit recording capabilities of a 100 microelectrode array.Brain Res 726:1-2, 129-40 (1996 Jul 8)

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ref: -0 tags: Cogan 2008 electrodes recording stimulation date: 02-05-2012 00:21 gmt revision:0 [head]

PMID-18429704 Neural stimulation and recording electrodes.

  • Electrical stimulation of nerve tissue and recording of neural electrical activity are the basis of emerging prostheses and treatments for spinal cord injury, stroke, sensory deficits, and neurological disorders. An understanding of the electrochemical mechanisms underlying the behavior of neural stimulation and recording electrodes is important for the development of chronically implanted devices, particularly those employing large numbers of microelectrodes. For stimulation, materials that support charge injection by capacitive and faradaic mechanisms are available. These include titanium nitride, platinum, and iridium oxide, each with certain advantages and limitations. The use of charge-balanced waveforms and maximum electrochemical potential excursions as criteria for reversible charge injection with these electrode materials are described and critiqued. Techniques for characterizing electrochemical properties relevant to stimulation and recording are described with examples of differences in the in vitro and in vivo response of electrodes.

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ref: Zaghloul-2009.03 tags: DBS STN reinforcement learning humans unexpected reward Baltuch date: 01-26-2012 18:19 gmt revision:1 [0] [head]

PMID-19286561[0] Human Substantia Nigra Neurons Encode Unexpected Financial Rewards

  • direct, concise.
  • 15 neurons in 11 patients -- we have far more!

____References____

[0] Zaghloul KA, Blanco JA, Weidemann CT, McGill K, Jaggi JL, Baltuch GH, Kahana MJ, Human substantia nigra neurons encode unexpected financial rewards.Science 323:5920, 1496-9 (2009 Mar 13)

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ref: Wiener-2008.08 tags: STN operant conditioning timing rats lesion DBS impulsivity date: 01-26-2012 17:29 gmt revision:3 [2] [1] [0] [head]

PMID-18562098[0] Accurate timing but increased impulsivity following excitotoxic lesions of the subthalamic nucleus.

  • Synopsis: Animals whose STNs were lesioned were able to maintain temporal control and response on a peak interval timing task, but they were unable to inhibit operant responses late into the trial. This suggests that STN may be used in impulse control / behavioral inhibition.

____References____

[0] Wiener M, Magaro CM, Matell MS, Accurate timing but increased impulsivity following excitotoxic lesions of the subthalamic nucleus.Neurosci Lett 440:2, 176-80 (2008 Aug 1)

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ref: Kuhn-2004.04 tags: STN LFP syncronization movement motor planning parkinsons PD DBS beta date: 01-26-2012 17:28 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

PMID-14960502[0] Event-related beta desynchronization in human subthalamic nucleus correlates with motor performance.

  • Asked 6 PD patients to play a game where they were warned to move / not to move.
  • Beta-frequency (20hz) power decreased prior to movement, with a time course correlated to reaction time.
    • This was followed by a late post-movement increase in beta power.
  • No-go trials showed a brief dip in beta power, with quick resumption.
  • conclude that:
    • the subthalamic nucleus is involved in the preparation of externally paced voluntary movements in humans
    • the degree of synchronization of subthalamic nucleus activity in the beta band may be an important determinant of whether motor programming and movement initiation is favored or suppressed. (hum, maybe).
  • found via Romulo's references; see the list of papers that cite it.

____References____

[0] Kühn AA, Williams D, Kupsch A, Limousin P, Hariz M, Schneider GH, Yarrow K, Brown P, Event-related beta desynchronization in human subthalamic nucleus correlates with motor performance.Brain 127:Pt 4, 735-46 (2004 Apr)

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ref: Wilson-2006.12 tags: parkinsons burst firing MPTP mice STN DBS date: 01-26-2012 17:25 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

PMID-16973296[0] Subthalamic nucleus neurones in slices from MPTP-lesioned mice show irregular, dopamine-reversible firing pattern changes, but without synchronous activity

  • loss of dopamine in parkinson-model rats (not MPTP!) induces synchronized low-frequency oscillatory burst-firing in subthalamic nucleus neurons
  • MPTP mice, neurons fire slower, and more irregularly
  • only dopamine varied (increased) firing rate.
  • the STN & GP are insufficient to generate the abberant firing patterns in the STN, by itself - the disease is more than just dopamine depletion.

____References____

[0] Wilson CL, Cash D, Galley K, Chapman H, Lacey MG, Stanford IM, Subthalamic nucleus neurones in slices from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mice show irregular, dopamine-reversible firing pattern changes, but without synchronous activity.Neuroscience 143:2, 565-72 (2006 Dec 1)

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ref: Foffani-2004.07 tags: STN motor preparation human 2003 basal_ganglia DBS SMA date: 01-26-2012 17:23 gmt revision:3 [2] [1] [0] [head]

PMID-15249649 Involvement of the human subthalamic nucleus in movement preparation

  • STN receives large afferent from SMA, so it should be involved in movement planning.
  • the STN and nearby structures are active before self-paced movements in humans.
  • normal patients show a negative EEG movement-related potential (MRP) starting 1-2 seconds before the onset of self-paced movements.
  • STN also shows premovement negative MRP.
    • REquire very sensitive methods to record this MRP -- it's on the order of 1 uv.
  • the amplitude of the scalp MRP is reduced in parkinson's patients.
    • impairment of movement preparation in PD may be related to deficits in the SMA and M1, e.g. underactivity.
    • the MRP is normalized with the administration of levodopa.
  • MPTP monkeys have increased activity in the STN
  • examined the role of the STN in movement preparation and inhibition via MRP recorded from DBS electrodes in the STN + simultaneously recorded scalp electrodes.
  • their procedure has the leads externalized during the first week after surgery.

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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: neuro notes-0 tags: STN globus_pallidus striatum diagram basal_ganglia date: 01-26-2012 17:16 gmt revision:1 [0] [head]

http://www.gpnotebook.co.uk/cache/-1248198589.htm (bitrotted)

  • note that the loop around both preserves sign, more or less, provided you take into account the D2 receptor along the 'indirect' pathway
  • this has some glaring flaws: the globus pallius external projects to the globus pallidus internal, cortex projects to STN, thalamus projects to striatum, etc.

http://www.portfolio.mvm.ed.ac.uk/studentwebs/session1/group71/john.htm

  • has a good diagram of the neurotransmitters involved in the motor selection pathway. need to understand the kinetics of the dopamine receptor family

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ref: Frank-2007.11 tags: horses PD STN DBS levodopa decision learning science date: 01-25-2012 00:50 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-17962524[0] Hold your horses: impulsivity, deep brain stimulation, and medication in parkinsonism.

  • While on DBS, patients actually sped up their decisions under high-conflict conditions. Wow!
    • This impulsivity was not effected by dopaminergic medication status.
    • Impulsivity may be the cognitive equivalent of excess grip force {88}.
  • Mathematical models of decision making suggest that individuals only execute a choice once the 'evidence' in its favor crosses a critical decision threshold.
    • people can adjust decision thresholds to meet current task demands
    • One theory is that the STN modulates decision thresholds (6) and delays decision-making when faced with a conflict. Wanted to test this in a conflict situation.
    • Record from the STN in conflict task to see ??
  • Second wanted to test negative learning.
    • Dopamine replacement therapy impairs patient's ability to learn from the negative outcomes of their decisions (11 - 13), which may account for pathological gambling behavior (14).
    • PD patients did indeed score worse on avoidance, slightly less accurate on AB choice, and about the same for the rest.
  • Made a network model.
    • Found that preSMA and STN coactivation is associated with slowed reaction times under decision conflict (25).
    • And that STN-DBS reduces coupling between cingulate and basal ganglia output (27).
    • Their model they either lesioned STN or overloaded it with high frequency regular firing.
      • either one showed the same faster response in high-conflict decisions.
  • STN dysfunction does not lead to impulsivity in all behavioral situations.
    • STN lesioned rats show enhanced preference for choices that lead to large delayed rewards compared to those that yield small immediate rewards (32,33). (This is not conflict, though -- rather reward -- but nonetheless illuminating)
  • Dopaminergic medication, by tonically elevating dopamine levels and stimulating D2 receptors, prevents learning from negative decision outcomes (11, 13, 18). Hence pathological gambling behavior (14).
  • Other studies show DBS-induced impairments in cognitive control (27 PMID-17119543, 36 PMID-15079009).

____References____

[0] Frank MJ, Samanta J, Moustafa AA, Sherman SJ, Hold your horses: impulsivity, deep brain stimulation, and medication in parkinsonism.Science 318:5854, 1309-12 (2007 Nov 23)

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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 ( alphaalpha MN) excitability when presynaptic inhibition and intrinsic excitability of the alphaalpha 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: Elble-1996.03 tags: tremor STN VIM thalamus basal_ganglia Elble Parkinson's ET dyskinesia thalamus VIM DBS date: 01-24-2012 21:19 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

PMID-8849968[] Central Mechanisms of Tremor -- available through Duke's Ovid system. also in email.

  • focuses at first on the nonlinear aspect of all control: the systems are hard to understand because of the complexities of their interactions.
    • nonlinear systems are capable of complex interactions that are not predicted by the sum of their individual behaviors.
  • in general, there are two different types of tremor:
    • mechanical reflex oscillations (depend on sensorimotor loops), permit damped oscillations in response to pulsate perturbations.
      • is effected by the stifness and inertia of the segment involved.
    • central oscillations
      • frequencies independent of limb mechanics/segment length.
      • still subject to modulation by sensorimotor feedback.
      • if the tremor is at the same frequency as the mechanical resonance, the tremor will be worse!
  • physiologic tremor has both components of mechanical oscillations (3-5Hz) and central oscillations (8-12hz), which are usually attenuated by the low-pass property of the musculoskeletal system.
    • associated spindle and tendon organ discharge are not sufficient to produce 8 - 12 Hz oscillation - hence, this is most likely from a central source, eg. the cortex, inferior olive, and thalamus.
  • Essential tremor is also centrally generated, though it appears to be affected by somatosensory driving.
    • essential tremor frequency is strongly correlated with patient age (where the frequency decreases with increasing age).
    • the origin of ET is unknown: postmortem examinations reveal no deficits in M1/S1, thalamus, inferior olive, raphe nucleus, and reticular nuclei, globus pallidus, and spinal cord...
    • but, the inferior olive seems to be the most likely culprit:
      • tremor induced by harmaline increased inhibition-rebound properties of neurons, and this induces intention-related tremor in monkeys
      • harmaline induced olivary oscillation is similar to ET in terms of frequency, EMG, and drug-response.
      • olivary hypothesis is supported by PET scans, which show increased glucose consumption there in ET patients.
      • the ventrolateral (VL) thalamus and Ventralis intermedius (VIM) receives input from the contralateral cerebellar nuclei.
        • this is why VIM is such a good target for treatment of ET.
  • parkinsons tremor:
    • VOP is a better target for treating bradykinesia and other symptoms of PD, while VIM is the best for treating tremor
    • neurons in the globus pallidus and STN become entrained to tremor. STN lesion / HFS is effective in treating dyskinesia and other PD symptoms.
    • in MPTP monkeys, STN/ GPi neurons are also entrained to the tremor frequency.
  • other tremor:
    • neuropathic/tumorogenic tremor usually takes weeks to appear, suggesting that CNS reorganization is a cause of tremor, not intrinsic sensorimotor deafferentation
      • local lesions in the striatum, thalamus, & globus pallidus often cause dystonias, not tremor.
  • Cerebellar tremor
    • seems to be caused by an inability to properly compensate/ brake with antagonist muscles during voluntary and postural movements. movement control becomes heavily dependent on sensory feedback, which is often too slow for adequate compensation.
  • neuroleptic drugs can often cause tremor (or tardive dyskinesia). Neurolepric - calming, tranquilizer, antipsychotic.
    • lithium can cause permanent tremor due to cerebellar gliosis!
  • VOP projects to the supplementary motor area (SMA) and dorsolateral prefrontal cortex (DLPFC) PMID-21629131 ; VIM projects to M1 & contralateral cerebellum, as mentioned above.

____References____

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ref: Dorval-2010.08 tags: DBS Dorval STN irregular regular basal ganglia model date: 01-24-2012 20:24 gmt revision:1 [0] [head]

PMID-20505125[0] Deep brain stimulation alleviates parkinsonian bradykinesia by regularizing pallidal activity.

  • Hypothesis: disorder in the STN leads to parkinsonian symptoms (tremor, akinesia).
  • finger tapping test.
  • Irregular DBS was less effective than regular DBS at eliminating bradykinesia.
  • computational model: this is because there are more transmission errors at thalamic output neurons.
    • computational model possibly fluffy to keep conclusion from being too short?
  • cf. [1][2] -- which includes an irregular stimulation protocol (at longer timescales).

____References____

[0] Dorval AD, Kuncel AM, Birdno MJ, Turner DA, Grill WM, Deep brain stimulation alleviates parkinsonian bradykinesia by regularizing pallidal activity.J Neurophysiol 104:2, 911-21 (2010 Aug)
[1] Rosin B, Slovik M, Mitelman R, Rivlin-Etzion M, Haber SN, Israel Z, Vaadia E, Bergman H, Closed-loop deep brain stimulation is superior in ameliorating parkinsonism.Neuron 72:2, 370-84 (2011 Oct 20)
[2] Santos FJ, Costa RM, Tecuapetla F, Stimulation on demand: closing the loop on deep brain stimulation.Neuron 72:2, 197-8 (2011 Oct 20)

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ref: BAdi-2009.09 tags: dopamine L-Dopa levodopa agonist young reward novelty punisment learning date: 01-24-2012 04:05 gmt revision:1 [0] [head]

PMID-19416950[0] Reward-learning and the novelty-seeking personality: a between- and within-subjects study of the effects of dopamine agonists on young Parkinson's patients

  • dopamine agonist administration in young patients with Parkinson's disease resulted in increased novelty seeking, enhanced reward processing, and decreased punishment processing may shed light on the cognitive and personality bases of the impulse control disorders, which arise as side-effects of dopamine agonist therapy in some Parkinson's disease patients.

____References____

[0] Bódi N, Kéri S, Nagy H, Moustafa A, Myers CE, Daw N, Dibó G, Takáts A, Bereczki D, Gluck MA, Reward-learning and the novelty-seeking personality: a between- and within-subjects study of the effects of dopamine agonists on young Parkinson's patients.Brain 132:Pt 9, 2385-95 (2009 Sep)

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ref: Parush-2011.01 tags: basal ganglia reinforcement learning hypothesis frontiers israel date: 01-24-2012 04:05 gmt revision:2 [1] [0] [head]

PMID-21603228[0] Dopaminergic Balance between Reward Maximization and Policy Complexity.

  • model complexity discounting is an implicit thing.
    • the basal ganglia aim at optimization of independent gain and cost functions. Unlike previously suggested single-variable maximization processes, this multi-dimensional optimization process leads naturally to a softmax-like behavioral policy
  • In order for this to work:
    • dopamine directly affects striatal excitability and thus provides a pseudo-temperature signal that modulates the tradeoff between gain and cost.

____References____

[0] Parush N, Tishby N, Bergman H, Dopaminergic Balance between Reward Maximization and Policy Complexity.Front Syst Neurosci 5no Issue 22 (2011)

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ref: Bonfanti-0 tags: wireless neural recording wireless italy date: 01-20-2012 05:30 gmt revision:3 [2] [1] [0] [head]

PMID-21096380[0] "A multi-channel low-power system-on-chip for single-unit recording and narrowband wireless transmission of neural signal."

  • Use Manchester-encoded FSK, with 20-sample spike extraction feeding 2kb RAM.
  • Feature sub-threshold biased transistors on input stage for low noise, and MOS-bipolar pseudo-resistors + 0.15pf caps as filter elements. see schematic.
  • 105uW / channel with the PA amplifier disabled.
    • Only 4uA/channel consumed in the input stage.
    • DSP consumes 400uA
    • VCO 400uA, PLL 300uA.
  • Has a brief but useful review of the other wireless neural recorders in this field -- including ultrawideband.

____References____

[0] Bonfanti A, Ceravolo M, Zambra G, Gusmeroli R, Spinelli AS, Lacaita AL, Angotzi GN, Baranauskas G, Fadiga L, A multi-channel low-power system-on-chip for single-unit recording and narrowband wireless transmission of neural signal.Conf Proc IEEE Eng Med Biol Soc 2010no Issue 1555-60 (2010)

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ref: BarGad-2003.12 tags: information dimensionality reduction reinforcement learning basal_ganglia RDDR SNR globus pallidus date: 01-16-2012 19:18 gmt revision:3 [2] [1] [0] [head]

PMID-15013228[] Information processing, dimensionality reduction, and reinforcement learning in the basal ganglia (2003)

  • long paper! looks like they used latex.
  • they focus on a 'new model' for the basal ganglia: reinforcement driven dimensionality reduction (RDDR)
  • in order to make sense of the system - according to them - any model must ingore huge ammounts of information about the studied areas.
  • ventral striatum = nucelus accumbens!
  • striatum is broken into two, rough, parts: ventral and dorsal
    • dorsal striatum: the caudate and putamen are a part of the
    • ventral striatum: the nucelus accumbens, medial and ventral portions of the caudate and putamen, and striatal cells of the olifactory tubercle (!) and anterior perforated substance.
  • ~90 of neurons in the striatum are medium spiny neurons
    • dendrites fill 0.5mm^3
    • cells have up and down states.
      • the states are controlled by intrinsic connections
      • project to GPe GPi & SNr (primarily), using GABA.
  • 1-2% of neurons in the striatum are tonically active neurons (TANs)
    • use acetylcholine (among others)
    • fewer spines
    • more sensitive to input
    • TANs encode information relevant to reinforcement or incentive behavior

____References____

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ref: Evarts-1968.01 tags: Evarts motor control pyramidal tract M1 PTN tuning date: 01-16-2012 18:59 gmt revision:4 [3] [2] [1] [0] [head]

PMID-4966614[] Relation of pyramidal tract activity to force exerted during voluntary movement

  • PTNs with high conduction velocity tend to be silent during motor quiescence and show phasic activity with movement.
  • PTNs with lower axonal conduction velocities are active in the absence of movement; with movement they show both upward and downward modulations of the resting discharge.
  • many PTNs responded to a conditional stimulus before the movement.
  • in this study, they wanted to determine if phasic response was more correlated with displacement or with force.
    • did this with two different motions (flexion and extension) in two different force loads (opposing flexion and opposing extransion)
      • movements were slow (or at least nonballistic) and somewhat controlled - they had to last between 400 and 700ms.
      • monkeys usually carried out 3,000 cycles of the movement daily !!
  • "prior to the experiment, hte authour was biased to think that the displacement model (where the cortex commands a location/movement of the arm, which is then accomplished through feedback & feedforward mechanisms e.g. in the spinal cord) was correct; experimental results seem to indicate that force is very strongly represented in PTN population.
  • many PTN firing rates reflected dF/dt very strongly.
  • old, good paper. made with 'primitive' technology - but why do we need to redo this?

____References____

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ref: Schwartz-1994.07 tags: Schwartz drawing spiral monkeys population vector PV date: 01-16-2012 18:52 gmt revision:1 [0] [head]

PMID-8036499[0] Direct cortical representation of drawing

____References____

[0] Schwartz AB, Direct cortical representation of drawing.Science 265:5171, 540-2 (1994 Jul 22)

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ref: Leach-2010.02 tags: BMI challenges histology biocompatibility review date: 01-16-2012 18:22 gmt revision:4 [3] [2] [1] [0] [head]

PMID-20161810[0] Bridging the Divide between Neuroprosthetic Design, Tissue Engineering and Neurobiology

  • Neuroprosthetic device technology has seen major advances in recent years but the full potential of these devices remains unrealized due to outstanding challenges, such as the ability to record consistently over long periods of time.
  • Discuss promising new treatments based on developmental and cancer biology (?)
  • Suggest controlled drug release as the tissue is healing. Makes sense.

____References____

[0] Leach JB, Achyuta AK, Murthy SK, Bridging the Divide between Neuroprosthetic Design, Tissue Engineering and Neurobiology.Front Neuroeng 2no Issue 18 (2010 Feb 8)

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ref: -0 tags: Najafi electrode spring dissolving Michigan date: 01-16-2012 17:55 gmt revision:1 [0] [head]

IEEE-5969351 (pdf) New class of chronic recording multichannel neural probes with post-implant self-deployed satellite recording sites

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ref: -0 tags: electrode implantation spring modeling muscles sewing date: 01-16-2012 17:30 gmt revision:0 [head]

PMID-21719340 Modelization of a self-opening peripheral neural interface: a feasibility study.

  • Electrode is self-opening, and they outline the math behind it. This could be useful!

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ref: Harrison-2003.06 tags: CMOS amplifier headstage electrophysiology neural_recording low_power chopper Reid Harrison date: 01-16-2012 04:43 gmt revision:12 [11] [10] [9] [8] [7] [6] [head]

IEEE-1201998 (pdf) A low-power low-noise CMOS amplifier for neural recording applications

  • detail novel MOS-bipolar pseudoresistor element to permit amplification of low-frequency signals down to milihertz range.
  • 80 microwatt spike amplifier in 0.16mm^2 silicon with 1.5 um CMOS, 1 microwatt EEG amplifier
  • input-referred noise of 2.2uV RMS.
  • has a nice graph comparing the power vs. noise for a number of other published designs
  • i doubt the low-frequency amplification really matters for neural recording, though certainly it matters for EEG.
    • they give an equation for the noise efficiency factor (NEF), as well as much detailed background.
    • NEF better than any prev. reported. Theoretical limit is 2.9 for this topology; they measure 4.8
  • does not compare well to Medtronic amp: http://www.eetimes.com/news/design/showArticle.jhtml?articleID=197005915
    • 2 microwatt! @ 1.8V
    • chopper-stabilized
    • not sure what they are going to use it for - the battery will be killed it it has to telemeter anything!
    • need to find the report for this.
  • tutorial on chopper-stabilized amplifiers -- they have nearly constant noise v.s. frequency, and very low input/output offset.
  • References: {1056} Single unit recording capabilities of a 100 microelectrode array. Nordhausen CT, Maynard EM, Normann RA.
  • [5] see {1041}
  • [9] {1042}
  • [12] {1043}
____References____

Harrison, R.R. and Charles, C. A low-power low-noise CMOS amplifier for neural recording applications Solid-State Circuits, IEEE Journal of 38 6 958 - 965 (2003)

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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: Mohseni-2005.09 tags: recording telemetry radio Najafi wireless date: 01-15-2012 22:22 gmt revision:3 [2] [1] [0] [head]

PMID-16200750[0] Wireless Multichannel Biopotential Recording Using an Integrated FM Telemetry Circuit Pedram Mohseni, Khalil Najafi, Steven Eliades, Xiaoquin Wang.

____References____

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ref: Kawano-2010.03 tags: mEA recording VLS silicon original date: 01-15-2012 22:11 gmt revision:3 [2] [1] [0] [head]

PMID-20089393[0] Electrical interfacing between neurons and electronics via vertically integrated sub-4 microm-diameter silicon probe arrays fabricated by vapor-liquid-solid growth.

  • The probe arrays can be fabricated on a silicon (1 1 1) substrate by selective VLS growth using catalytic-gold (Au) dots and a disilane (Si2H6) gas source, allowing precise control of probe position, diameter and length, as well as on-chip interconnections/integrated circuits (ICs) ( [Wagner and Ellis, 1964], [Ishida et al., 1999] and [Kawano et al., 2002])
  • maximum length 120 um (or so)

____References____

[0] Kawano T, Harimoto T, Ishihara A, Takei K, Kawashima T, Usui S, Ishida M, Electrical interfacing between neurons and electronics via vertically integrated sub-4 microm-diameter silicon probe arrays fabricated by vapor-liquid-solid growth.Biosens Bioelectron 25:7, 1809-15 (2010 Mar 15)

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ref: Chestek-2007.1 tags: M1 cortex reaching tuning date: 01-15-2012 22:08 gmt revision:1 [0] [head]

PMID-17913908[0] Single-Neuron Stability during Repeated Reaching in Macaque Premotor Cortex

  • Neural activity was predominantly stable over time in all measured properties: firing rate, directional tuning, and contribution to a decoding model that predicted kinematics from neural activity. The small changes in neural activity that we did observe could be accounted for primarily by subtle changes in behavior. We conclude that the relationship between neural activity and practiced behavior is reasonably stable, at least on timescales of minutes up to 48 h.
    • Makes sense.
    • Good for neuroprosthetics.

____References____

[0] Chestek CA, Batista AP, Santhanam G, Yu BM, Afshar A, Cunningham JP, Gilja V, Ryu SI, Churchland MM, Shenoy KV, Single-neuron stability during repeated reaching in macaque premotor cortex.J Neurosci 27:40, 10742-50 (2007 Oct 3)

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ref: Kim-2009.04 tags: Utah ASIC recording 2009 date: 01-15-2012 22:08 gmt revision:1 [0] [head]

PMID-19067174[0] Integrated wireless neural interface based on the Utah electrode array

  • Describes their fully integrated 100 site Utah probe.
  • "A planar power receiving coil fabricated by patterning electroplated gold films on polyimide substrates was connected to the IC by using a custom metallized ceramic spacer and SnCu reflow soldering. The SnCu soldering was also used to assemble SMD capacitors on the UEA. "

____References____

[0] Kim S, Bhandari R, Klein M, Negi S, Rieth L, Tathireddy P, Toepper M, Oppermann H, Solzbacher F, Integrated wireless neural interface based on the Utah electrode array.Biomed Microdevices 11:2, 453-66 (2009 Apr)

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ref: Holleman-2007.08 tags: amplifier recording NEF low noise original date: 01-15-2012 22:08 gmt revision:1 [0] [head]

IEEE-4353193 (pdf) A Sub-Microwatt Low-Noise Amplifier for Neural Recording

  • 0.805 uA from a 1V supply, gain of 36dB and 44db.
  • open loop amplfier, pass band between 0.3 and 4.7 kHz.
  • 3.5 uV rms input referred noise.
  • NEF 1.8

____References____

Holleman, J. and Otis, B. Engineering in Medicine and Biology Society, 2007. EMBS 2007. 29th Annual International Conference of the IEEE 3930 -3933 (2007)

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ref: Farshchi-2006.07 tags: recording COTS date: 01-15-2012 22:08 gmt revision:1 [0] [head]

IEEE-1643411 (pdf) A TinyOS-enabled MICA2-BasedWireless neural interface

  • six channels, 9.6 kbps, 66 mW power.
  • TinyOS based.

____References____

Farshchi, S. and Nuyujukian, P.H. and Pesterev, A. and Mody, I. and Judy, J.W. A TinyOS-enabled MICA2-BasedWireless neural interface Biomedical Engineering, IEEE Transactions on 53 7 1416 -1424 (2006)

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ref: Sodagar-2009.09 tags: ASIC recording Najafi spike sorting date: 01-15-2012 22:07 gmt revision:4 [3] [2] [1] [0] [head]

IEEE-5226763 (pdf) An Implantable 64-Channel Wireless Microsystem for Single-Unit Neural Recording

  • Spike sorting (thresholding) on 64 channels, 8 bit digitization, 62.5 ks/sec, 60dB gain, 14.4 mW at 1.8V.
  • 1.4 by 1.55 cm.

____References____

Sodagar, A.M. and Perlin, G.E. and Ying Yao and Najafi, K. and Wise, K.D. An Implantable 64-Channel Wireless Microsystem for Single-Unit Neural Recording Solid-State Circuits, IEEE Journal of 44 9 2591 -2604 (2009)

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ref: Obeid-2004.02 tags: Obeid multichannel telemetry wireless recording date: 01-15-2012 22:06 gmt revision:3 [2] [1] [0] [head]

PMID-14757342[0] A multichannel telemetry system for single unit neural recordings

  • 16 channels; only transmit 12.
  • 45 minute battery life, 4W power consumption.
  • Uses a 486 index-card sized PC running DOS.
    • TCP/IP connection from host PC to wearable computer; UDP transmission of neural data.
  • 802.11b via a WAN ethernet card
  • 235g
  • AFE see [1]
  • 100mW radiated power.
  • Latency 680us input to output.
  • Did not notice any problems due to multipath.
  • See also PMID-17945926[2] for similar work

____References____

[0] Obeid I, Nicolelis MA, Wolf PD, A multichannel telemetry system for single unit neural recordings.J Neurosci Methods 133:1-2, 33-8 (2004 Feb 15)
[1] Obeid I, Nicolelis MA, Wolf PD, A low power multichannel analog front end for portable neural signal recordings.J Neurosci Methods 133:1-2, 27-32 (2004 Feb 15)
[2] Parthasarathy J, Hogenson J, Erdman AG, Redish AD, Ziaie B, Battery-operated high-bandwidth multi-channel wireless neural recording system using 802.11b.Conf Proc IEEE Eng Med Biol Soc 1no Issue 5989-92 (2006)

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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: Wattanapanitch-2007 tags: recording tech amplifier cascode MOS-bipolar pseudoresistor MIT date: 01-15-2012 18:13 gmt revision:5 [4] [3] [2] [1] [0] [head]

IEEE-4358095 (pdf) An Ultra-Low-Power Neural Recording Amplifier and its use in Adaptively-Biased Multi-Amplifier Arrays.

  • images/729_1.pdf -- copy, just in case.
  • Masters thesis - shows the development of, as the title explains, an ultra low power neural amplifier.
  • Probably the best amplifier out there. NEF 2.67; theoretical limit 2.02.
  • Final design uses folded cascode operational transconductance amplifier (OTA)
    • Design employs a capacitor-feedback gain stage of 40db followed by a lowpass stage.
    • Majority of the current is passed through large subthreshold PMOS input transistors.
      • PMOS has lower noise than NMOS in most processes.
      • Subthreshold has the highest transconductance-to-current ratio. (ratio of a ratio)
    • Cascode transistors self-shunt their own current noise sources.
    • Design takes 0.16 mm^2 in 0.5 um AMI CMOS process, uses 2.7 uA from a ~2.8V supply, input referred noise of 3 uVrms
    • Thesis gives all design parameters for the transistors.
    • Input is AC coupled, DC path through gigaohm MOS-bipolar psudoresistor.
      • this path gracefully decays to diode-connected MOS or bipolar transistors if the voltage is high.
    • images/729_1.pdf
  • Last chapter details the use of envelope detection to adaptively change the bias current of the input stage
    • That is, if an electrode is noisy, the bias current is decreased!

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ref: Hoogerwerf-1994.12 tags: Wise Michigan array MEA recording 3D date: 01-15-2012 07:12 gmt revision:4 [3] [2] [1] [0] [head]

IEEE-335862 (pdf) A three-dimensional microelectrode array for chronic neural recording.

  • see {995} for reasonable photos (they don't show up in the black and white IEEE scan).
  • 16-channel, 4 shanks.
  • 3D : 16 shanks, 64 channels, includes a 16:1 MNOS mux on the attached micromachined silicon platform.
  • Nickel plated lead stransfers (90 deg) see figure 6 electroplating current.
    • This was a point of difficulty, it seems.

____References____

Hoogerwerf, A.C. and Wise, K.D. A three-dimensional microelectrode array for chronic neural recording Biomedical Engineering, IEEE Transactions on 41 12 1136 -1146 (1994)

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ref: BeMent-1986.02 tags: Najafi Michigan probe recording silicon MEA date: 01-15-2012 06:59 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

PMID-3957372[0] Solid-state electrodes for multichannel multiplexed intracortical neuronal recording.

  • 1986 (!!) - but same basic technology for manufacture of these devices. Modern Michigan probes are much smaller, though - this paper uses 6um feature sizes. It seems like the rate-limiting step for a lot of this is marketization/selling it & getting the money for further R&D.
  • Mention closed-loop neuroprotheses ... 26 years ago. Why do we not have this yet? This is a really important question!
  • 12 channel on-chip analog processing, G=100, bandwidth 100-6kHz.
  • Mention that they think most of the current has to flow around other cells (glia), which makes it possible to record considerably further from the soma (ref [1],); see also PMID-14490040 which through modeling claims much smaller spread of current.
  • Electrode sites are highly capacitive, phase angle 80 deg.
  • 8 um interconnect leads.
  • Enhancement-mode LOCOS NMOS process.

____References____

[0] BeMent SL, Wise KD, Anderson DJ, Najafi K, Drake KL, Solid-state electrodes for multichannel multiplexed intracortical neuronal recording.IEEE Trans Biomed Eng 33:2, 230-41 (1986 Feb)

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ref: Vibert-1979.08 tags: spike sorting recording depth extracellular glass electrodes active feedback original date: 01-15-2012 06:46 gmt revision:3 [2] [1] [0] [head]

PMID-95711[0] Spike separation in multiunit records: A multivariate analysis of spike descriptive parameters

  • Glass coated tungsten microeletrodes have high capacitance; they compensate for this by spraying colloidal silver over the outside sheath of the glass, insulating that with varnish, and driving the shield in a positive-feedback way (stabillized in some way?) This negates the capacitance. 'low impedance capacitance compensated'.
    • Capacitance compensation really matters!!
  • Were able to record from single units for 40-100um range (average: 50um) with SNRs 2:1 to 7:1.
    • Some units had SNRs that could reach 15:1 (!!!), these could be recorded for 600 um of descent.
    • more than 3 units could usually be recognized at each recording point by visual inspection of the oscilloscope, and in some cases up to 6 units could be distinguished
    • Is there some clever RF way of neutralizing the capacitance of everything but the electrode tip? Hmm. Might as well try to minimize it.
  • Bandpass 300 Hz - 10 kHz.
  • When the signal crossed the threshold level, it was retained and assumed to be a spike if the duration of the first component was between 70 and 1000 us.
    • This 70 us lower limit was determined on a preliminary study as a fairly good rise time threshold for separation of fiber spikes from somatic or dendritic spikes.
    • I really need to do some single electrode recordings. Platt?
  • Would it be possible to implement this algorithm in realtime on the DSP?
  • Describe clustering based on PCA.
  • Programming this computer (PDP-12) must have been crazy!
  • They analyzed 20k spikes. Mango gives billions.
  • First principal component (F1) represented 60-65% of total information was based mostly on amplitude
  • Second principal component, 15-20% of total information represented mainly time parameters.
  • Suggested 3 parameters: Vmax, Vmin, and T3 (time from max to min).
  • Maybe they don't know what they are talking about:

____References____

[0] Vibert JF, Costa J, Spike separation in multiunit records: a multivariate analysis of spike descriptive parameters.Electroencephalogr Clin Neurophysiol 47:2, 172-82 (1979 Aug)

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ref: Olsson-2005.12 tags: recording Olsson Wise sorting date: 01-15-2012 06:04 gmt revision:3 [2] [1] [0] [head]

IEEE-1546254 (pdf) A three-dimensional neural recording microsystem with implantable data compression circuitry

  • quite a bit of engineering in this one!
  • 256 site
  • spike detection ASIC which transmits a parameterized version of the threshold crossings.
  • Only consumes 5.4mW total. wow.
  • outgoing bandwidth 2.5 Mb/sec.
  • Only allows spike detection on 32 of these sites
    • The mux is also limited to common groups to minimize consumed space.
  • 5 bit spike detection ADC.
  • 12.6uV RMS noise.
  • Unidirectional link -- sets threshold automatically.
  • 8:1 channel mux changes on both positive and negative clocks, which prevents clock transitions in the middle of the sampling window.
    • Measure crosstalk 6% or less -- really?
  • Vibert [16] evaluated neural spike separation baseed on eight parameters and concluded that using three parameters, Vmax (the maximum positive spike amplitude), Vmin (the minimum negative spike amplitude) and T (the time between Vmax and Vmin) not only adequately sorted spikes but was superior to separation using more parameters. Other parameters were found to be correlated with Vmax, Vmin, and T, whereas Vmax Vmin and T were uncorrelated.

____References____

Olsson, R.H., III and Wise, K.D. A three-dimensional neural recording microsystem with implantable data compression circuitry Solid-State Circuits, IEEE Journal of 40 12 2796 - 2804 (2005)

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ref: Schmidt-1984.11 tags: spike sorting Schmidt date: 01-15-2012 05:45 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-6392757[0] Instruments for sorting neuroelectric data: a review

  • Seems like it would be useful for me :-)
  • Amplifier bandwidth should be between 5 and 7.5kHz
  • High-pass between 100 and 600Hz, to reduce the 'baseline hash produced by the firing of distant neurons.
  • Electrodes generate Johnson noise (same as thermal noise): E=0.1219R×BμVrms E = 0.1219 \sqrt{R \times B} \mu V rms , where B = bandwidth in Hz and R = resistance in MOhm.
  • Modern low-noise FET amplifiers produce noise equivalent to a source resistance of 15K
  • Describe a number of nonlinear spike detection filters using switched amplifiers; these do not seem to have survived.
  • Analog window comparators described have been largely replaced with digital filtering techniques.
    • That said, the use of photo-detectors taped to an oscilloscope is an ingenious method for spike discrimination!
  • Note that audio output is useful, too. Ear is a good discriminator.

____References____

[0] Schmidt EM, Instruments for sorting neuroelectric data: a review.J Neurosci Methods 12:1, 1-24 (1984 Nov)

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ref: Dorman-1985.12 tags: recording ASIC wireless date: 01-15-2012 05:35 gmt revision:2 [1] [0] [head]

IEEE-1052457 (pdf) A monolithic signal processor for a neurophysiological telemetry system

    • 8 channels.
    • 11 mW.
    • 12 cm^3 volume.
    • 900 pF or nitride-dielectric capacitance.
  • FM telemetry. consumes 75% of the system power in high bandwidth mode.
    • 8 cm^3 2.5 AH LiIon.
    • Some very clever stuffs with forward-biased diodes (picoamps, 10^10 ohms) to get the filtering...
    • Abstract: A micropower signal-processor IC is the key component of an implantable telemetry system for neurophysiology. The bipolar/JFET/I/SUP 2/L chip uses digital and low-noise analog circuitry to amplify, filter, and multiplex eight channels of neutral, electrogram, and temperature data from unanesthetized and freely moving animals. Fully integrated continuous-time bandpass amplifiers incorporate a frequency-sensitive feedback network to prevent the amplification of input offset voltage. The system can telemeter data for over 500 h, permitting long-term neurophysiological investigations.

____References____

Dorman, M.G. and Prisbe, M.A. and Meindl, J.D. A monolithic signal processor for a neurophysiological telemetry system Solid-State Circuits, IEEE Journal of 20 6 1185 - 1193 (1985)

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ref: Ji-1992.03 tags: recording ASIC Michigan date: 01-15-2012 05:32 gmt revision:1 [0] [head]

IEEE-121568 (pdf) An implantable CMOS circuit interface for multiplexed microelectrode recording arrays

  • 15 uV RMS input-referred noise (high!), 8 channels, AC gain 300 15Hz - 7kHz, 2.5 mW, 3um feature size.
  • Self-test features.

____References____

Ji, J. and Wise, K.D. ''An implantable CMOS circuit interface for multiplexed microelectrode recording arrays'' Solid-State Circuits, IEEE Journal of 27 3 433 -443 (1992)

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ref: Dagtekin-2001 tags: recording chopper asic date: 01-15-2012 05:32 gmt revision:3 [2] [1] [0] [head]

IEEE-1019051 (pdf) A multi channel chopper modulated neural recording system

  • Presented herein is a fully integrated low-noise CMOS multi-channel amplifier for neural recording applications. The circuit employs the chopper modulation technique to reduce the effect of flicker noise and DC offset. A reduced area design implementation is achieved by trading off the increased noise margin performance of the chopper modulator for minimal amplifier area and analog multiplexing of the recording sites. A fully differential topology is used for the signal path to improve noise immunity. The analog amplifier exhibits 56 dB of gain with a 115 kHz bandwidth and a common mode rejection ratio (CMRR) of 80 dB. Simulation results show a total input referred noise less than 16 nV/√Hz. The system power consumption is approximately 750 μWatts. The fully integrated system was designed in ABN 1.6-μm single poly n-well CMOS process.

____References____

Dagtekin, M. and Wentai Liu and Bashirullah, R. Engineering in Medicine and Biology Society, 2001. Proceedings of the 23rd Annual International Conference of the IEEE 1 757 - 760 vol.1 (2001)

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ref: Guillory-1999.09 tags: recording spike sorting Utah date: 01-15-2012 05:32 gmt revision:2 [1] [0] [head]

PMID-10522821[0] A 100-channel system for real time detection and storage of extracellular spike waveforms.

  • Large, non-wireless, 100 channel recording system.
  • Spike snippet extraction
  • Base 5 multiplexing (??)
  • 1uv input-referred noise.
  • also 88 instructions per sample with their 66Mhz DSP.
  • Windows GUI. all of this much like my work, actually. except not wireless.
  • 1999. hard to remember that a 200 Mhz PC was state of the art back then (!!)

____References____

[0] Guillory KS, Normann RA, A 100-channel system for real time detection and storage of extracellular spike waveforms.J Neurosci Methods 91:1-2, 21-9 (1999 Sep 15)

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ref: Obeid-2003.02 tags: Obeid integrated circuits recording Morizio Nicolelis date: 01-15-2012 04:35 gmt revision:2 [1] [0] [head]

IEEE-1185151 (pdf) Two multichannel integrated circuits for neural recording and signal processing

  • pretty basic, nothing tricky. Actually, they are rather scarce with the details -- Morizio?
  • all 16 capacitors are placed off chip; on chip capacitors are only 950e-18 F/um^2 or 0.001pF/um^2 in the process they use.
  • designs with this circuit topology were rejected for noise concerns, as they would require resistors as large as 10G for to realize gain and filter cutoff.
    • and yet Reid's chips seem to be working fine without external capcitors ...
  • have variable gain (but not AGC).
  • 5uV RMS input noise; 3.5uV for the plexon headstage.

____References____

Obeid, I. and Morizio, J.C. and Moxon, K.A. and Nicolelis, M.A.L. and Wolf, P.D. Two multichannel integrated circuits for neural recording and signal processing Biomedical Engineering, IEEE Transactions on 50 2 255 -258 (2003)

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ref: Mojarradi-2003.03 tags: MEMS recording telemetry Normann Andersen wireless date: 01-15-2012 04:29 gmt revision:2 [1] [0] [head]

PMID-12797724[0] A miniaturized neuroprosthesis suitable for implantation into the brain.

  • Standard tricks: cascode configuration, deep-ohmic PMOS Devices for resistive feedback, wide PMOS weak-inversion input stage for good transconductance and low noise.
  • Varaible power for variable noise levels & bandwidths.
  • Wireless transceiver and power stage are in early concept stages.

____References____

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ref: Song-2009.08 tags: wireless neural recording RF Brown laser optical Donoghue date: 01-15-2012 00:58 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

IEEE-5067358 (pdf) Wireless, Ultra Low Power, Broadband Neural Recording Microsystem

  • 16 channels.
  • Use a VCSEL (vertical cavity surface emission laser) to transmit data through the skin.
  • Nice design, and they claim to have made recordings for 1 month already.
  • One PCB, kapton substrate reinforced with alumina where needed.
  • Custom 12mW neural amplifier.

____References____

Song, Y.-K. and Borton, D.A. and Park, S. and Patterson, W.R. and Bull, C.W. and Laiwalla, F. and Mislow, J. and Simeral, J.D. and Donoghue, J.P. and Nurmikko, A.V. Active Microelectronic Neurosensor Arrays for Implantable Brain Communication Interfaces Neural Systems and Rehabilitation Engineering, IEEE Transactions on 17 4 339 -345 (2009)

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ref: Ganguly-2009.07 tags: Ganguly Carmena 2009 stable neuroprosthetic BMI control learning kinarm date: 01-14-2012 21:07 gmt revision:4 [3] [2] [1] [0] [head]

PMID-19621062 Emergence of a stable cortical map for neuroprosthetic control.

  • Question: Are the neuronal adaptations evident in BMI control stable and stored like with skilled motor learning?
    • There is mixed evidence for stationary neuron -> behavior maps in motor cortex.
      • It remains unclear if the tuning relationship for M1 neurons are stable across time; if they are not stable, rather advanced adaptive algorithms will be required.
  • A stable representation did occur.
    • Small perturbations to the size of the neuronal ensemble or to the decoder could disrupt function.
    • Compare with {291} -- opposite result?
    • A second map could be learned after primary map was consolidated.
  • Used a Kinarm + Plexon, as usual.
    • Regressed linear decoder (Wiener filter) to shoulder and elbow angle.
  • Assessed waveform stability with PCA (+ amplitude) and ISI distribution (KS test).
  • Learning occurred over the course of 19 days; after about 8 days performance reached an asymptote.
    • Brain control trajectory to target became stereotyped over the course of training.
      • Stereotyped and curved -- they propose a balance of time to reach target and effort to enforce certain firing rate profiles.
    • Performance was good even at the beginning of a day -- hence motor maps could be recalled.
  • By analyzing neuron firing wrt idealized movement to target, the relationship between neuron & movement proved to be stable.
  • Tested to see if all neurons were required for accurate control by generating an online neuron dropping curve, in which a random # of units were omitted from the decoder.
    • Removal of 3 neurons (of 10 - 15) resulted in > 50% drop in accuracy.
  • Tried a shuffled decoder as well: this too could be learned in 3-8 days.
    • Shuffling was applied by permuting the neurons-to-lags mapping. Eg. the timecourse of the lags was not changed.
  • Also tried retraining the decoder (using manual control on a new day) -- performance dropped, then rapidly recovered when the original fixed decoder was reinstated.
    • This suggests that small but significant changes in the model weights (they do not analyze what) are sufficient for preventing an established cortical map from being transformed to a reliable control signal.
  • A fair bit of effort was put into making & correcting tuning curves, which is problematic as these are mostly determined by the decoder
    • Better idea would be to analyze the variance / noise properties wrt cursor trajectory?
  • Performance was about the same for smaller (10-15) and larger (41) unit ensembles.

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ref: -0 tags: mango date: 01-12-2012 21:25 gmt revision:3 [2] [1] [0] [head]

Below, scatter plots of cursor position for each of the 4 corner targets. That is, upper right plot was when the upper right target was present, etc. Data only from when the mk was paying attention.

First plot: Dec 16 2011, 'early' 2D BMI session. Occupancy for each of the targets is about the same, with slightly higher occupancy for off-diagonal targets.

Second plot: Dec 21 2011, 'less early' 2D BMI session. Occupancy is skewed for left and top right targets, but not for bottom right. Likely this is because he found it hard to reach this target, as neurons controlling X and Y directions were correlated.

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ref: Santhanam-2007.11 tags: HermesB Shenoy continuous neural recording Utah probe flash wireless date: 01-09-2012 00:00 gmt revision:4 [3] [2] [1] [0] [head]

PMID-18018699[0] HermesB: a continuous neural recording system for freely behaving primates.

  • saved the data to compact flash. could record up to 48 hours continuously.
  • recorded from an acceleromter, too - neuron changes were associated with high head accelerations (unsurprisingly).
  • also recorded LFP, and were able to tell with some accuracy what behavioral state the monkey was in.
  • interfaces to the Utah probe
  • not an incredibly small system, judging from the photos.
  • 1600maH battery, 19 hour life @ 2/3 recording duty cycle -> current draw is 120mA, or 450mW.
    • can only record from two channels at once!
    • amplifier gain 610.
    • used ARM microcontroller ADUC2106

____References____

{779}
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ref: Song-2005.06 tags: recording wireless silicon utah probe Donoghue 2005 date: 01-08-2012 23:24 gmt revision:3 [2] [1] [0] [head]

PMID-16003903[0] Development of a chipscale integrated microelectrode/microelectronic device for brain implantable neuroengineering applications.

-- second from this

  • They have mated a 16-channel silicon microprobe to a low-power (50uW/channel) VLSI chip, including a CMOS amplifier.
    • Epoxy ball-bond.
    • 7mW total power.
  • Suggest photovoltaic power using GaAs/AlGaAs photodiodes. 3 in series yielding 3V at about 20% efficiency. Not bad! Then they can use the fiber to get data out, too.

____References____

[0] Song YK, Patterson WR, Bull CW, Beals J, Hwang N, Deangelis AP, Lay C, McKay JL, Nurmikko AV, Fellows MR, Simeral JD, Donoghue JP, Connors BW, Development of a chipscale integrated microelectrode/microelectronic device for brain implantable neuroengineering applications.IEEE Trans Neural Syst Rehabil Eng 13:2, 220-6 (2005 Jun)

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ref: Bossetti-2004.06 tags: Bossetti wolf Carmena Nicolelis latency wireless BMI recording date: 01-08-2012 21:16 gmt revision:2 [1] [0] [head]

IEEE-1300783 (pdf) Transmission latencies in a telemetry-linked brain-machine interface

  • quote: "examines the relationships between the ratio of output to average input bandwidth of an implanted device and transmission latency and required queue depth".
  • can use to explain why I decided on the fixed-bandwidth method. must measure the latency on my system .. how?
  • firing bursts results in high latencies in a variable-bandwidth queued system.
  • Tested in 32-neuron ensemble.
  • require output bandwidth / input bandwidth to be at least 4 to get sub-10ms max latency.

____References____

Bossetti, C.A. and Carmena, J.M. and Nicolelis, M.A.L. and Wolf, P.D. Transmission latencies in a telemetry-linked brain-machine interface Biomedical Engineering, IEEE Transactions on 51 6 919 -924 (2004.06)

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ref: Carmena-2003.11 tags: Carmena nicolelis BMI learning 2003 date: 01-08-2012 18:53 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-14624244[0] Learning to control a brain-machine interface for reaching and grasping by primates.

  • strong focus on learning & reorganization.
  • Jose's first main paper.
  • focuses on two engineering / scientific questions: what signal to use, and how much of it, and from where.
    • As for where, of course we suggest that the representation is distributed.
  • Quality of predictions: gripping force > hand velocity > hand position.
  • Showed silent EMGs during BMI control.
  • Put a robot in the feedback path; this ammounted for some nonlinearities + 60-90ms delay.
  • Predictions follow anatomical expectation:
    • M1 (33-56 cells) predicts 73% variance for hand pos, 66% velocity, 83% for gripping force .
    • SMA (16-19 cells) 51% position, 51% velocity, 19% gripping force.
    • They need a table for this shiz.
  • Relatively high-quality predictions. (When I initially looked at the data, I was frustrated with the noise!)
  • Learning was associated with increased contribution of single units.
    • appeared to be more 'learning' in SMA.
    • Training on a position model seemed to increase the ctx representation of hand position.
  • changes between pole control and brain control:
    • 68% of of sampled neurons showed reduced tuning in BCWOH
    • 14% no change
    • 18% enhanced tuning.
  • Directional tuning curves clustered in a band during brain control -- neurons clustering around the first PC?
    • All cortical areas tested showed increases in correlated firing -- arousal?
    • this puts some movements into the nullspace of the Wiener matrix. Or does it? should have had the monkey make stereotyped movements to dissociate movement directions.
  • Knocks {334} in that:
    • preferred directions were derived not from actual movements, but from firing rates during target appearance time windows.
    • tuning strength could have increased simple because the movements became straighter with practice.
  • From Fetz, {329}: Interestingly, the conversion parameters obtained for one set of trials provided increasingly poor predictions of future responses, indicating a source of drift over tens of minutes in the open-loop condition. This problem was alleviated when the monkeys observed the consequences of their neural activity in ‘real time’ and could optimize cell activity to achieve the desired goal under ‘closed-loop’ conditions.

____References____

{308}
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ref: Kipke-2003.06 tags: Michigan rat Kipke recording electrode MEA date: 01-08-2012 03:34 gmt revision:5 [4] [3] [2] [1] [0] [head]

IEEE-1214707 (pdf) Silicon-substrate intracortical microelectrode arrays for long-term recording of neuronal spike activity in cerebral cortex.

  • 4 of the 6 implants (66%) remaining functional for more than 28 weeks (7 mo)
  • Recording sites separated by 100um; at this site separation, adjacent sites may sometimes record the same unit.
  • It is notable that in each case in this series was terminated due to reasons other than the microelectrode not recording unit activity. (SC LIn agrees, pc).
  • around 80% of sites recorded neural activity.

____References____

{989}
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ref: Li-2009.07 tags: Zheng Odoherty Nicolelis unscented kalman wiener filter date: 01-07-2012 23:57 gmt revision:1 [0] [head]

PMID-19603074[0] Unscented Kalman filter for brain-machine interfaces.

  • Includes quadratic neuron tuning curves.
  • Includes n-1 past states for augmented state prediction.
  • Population vector .. has < 0 SNR.
  • Works best with only 1 future tap .. ?
  • Pursuit and center-out tasks.

____References____

[0] Li Z, O'Doherty JE, Hanson TL, Lebedev MA, Henriquez CS, Nicolelis MA, Unscented Kalman filter for brain-machine interfaces.PLoS One 4:7, e6243 (2009 Jul 15)

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ref: Wyler-1980.08 tags: Wyler operant conditioning fast slow pyramidal tract neurons BMI date: 01-07-2012 22:09 gmt revision:3 [2] [1] [0] [head]

PMID-7409057[0] Operant control of precentral neurons: comparison of fast and slow pyramidal tract neurons.

  • Slow PTN (neurons with antidromic latency > 2ms) are pratically all well controlled in his operant-conditioning task;
  • Fast (< 2ms, mean 1.2ms latency) have a more highly variable firing rates and ISIs.
  • "[I]t appears that the majority of error from fast PT cells was generated by ISIS less than 30 ms, whereas the majority of error for slow PT cells was represented in ISIS greater than 60 ms."
    • Ok, trivial observation, but still interesting.

____References____

[0] Wyler AR, Burchiel KJ, Robbins CA, Operant control of precentral neurons: comparison of fast and slow pyramidal tract neurons.Exp Neurol 69:2, 430-3 (1980 Aug)

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ref: Wyler-1980.05 tags: operant control motor learning interspike intervals ISI Wyler Lange Neafsey Robbins date: 01-07-2012 21:46 gmt revision:1 [0] [head]

PMID-6769536[0] Operant control of precentral neurons: Control of modal interspike intervals

  • Question: can monkeys control the ISI of operantly controlled neurons?
    • Answer: Seems they cannot. Operant and overt movement cells have about the same ISI, and this cannot be changed by conditioning.
  • Task requires a change from tonic to phasic firing, hence they call it "Differential reinforcement of Tonic Patterns".
    • That is, the monkey is trained to produce spikes within a certain ISI window.
    • PDP8 control, applesauce feedback.
    • modal ISI, in this case, means mode (vs. mean and median) of the ISI.
  • Interesting: "It was not uncommon for a neuron to display bi- or trimodal ISI distributions when the monkey was engaged in a movement unrelated to a unit's firing"
  • For 80% of the units, the more tightly a neuron's firing was related to a specific movement, the more gaussian its ISI became.
  • As the monkey gained control over reinforced units, the ISI became more gaussian.
  • Figure 2: monkey was not able to significantly change the modal ISI.
    • Monkeys instead seem to succeed at the task by decreasing the dispersion of the ISI distribution and increasing the occurrence of the modal ISI.
  • Monkeys mediate response through proprioceptive feedback:
    • Cervical spinal cord sectioning decreases the fidelity of control.
    • When contralateral C5-7 ventral roots were sectioned, PTN responsive to passive arm movements could not be statistically controlled.
    • Thus, monkeys operantly control precentral neurons through peripheral movements, perhaps even small and isometric contractions.
  • Excellent paper. Insightful conclusions.

____References____

[0] Wyler AR, Lange SC, Neafsey EJ, Robbins CA, Operant control of precentral neurons: control of modal interspike intervals.Brain Res 190:1, 29-38 (1980 May 19)

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ref: Fetz-1973.03 tags: operant conditioning Fetz Baker learning BMI date: 01-07-2012 19:34 gmt revision:2 [1] [0] [head]

PMID-4196269[0] Operantly conditioned patterns on precentral unit activity and correlated responses in adjacent cells and contralateral muscles

  • Looked at an operant task through the opposite direction: as a means for looking at reaction time, and muscle responses to trained bursts of activity.
  • recorded from precentral gyrus cells in leg and arm representation.
    • isonel coated tungsten microwires, with great apparent waveform records.
  • also recorded EMG, nylon-insuldated stainless-steel wire, led subcutaneuosly to the head connector.
  • references an even older study concerning the operant conditioning of neural activity in rats by Olds.
  • really simple technology - RC filter to estimate the rate; reward high rate; resets on reward.
    • the evoked operant bursts are undoubtably due to training.
  • looks like it was easy for the monkeys to increase the firing rate of their cortical cells (of course, I'm just skimming the article..)
  • 233 precentral units.
    • which they did some preliminary somatotopic mapping of.
  • neighboring cells mirrored the firing rate changes (logical as they share the local circuitry)
  • in a few sessions the operant bursts were not associated with movements.
  • Could individually condition cells when they happened to record 2 units on the same electrode.

____References____

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ref: Fetz-1969.02 tags: BMI original Fetz operant conditioning date: 01-07-2012 19:04 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

PMID-4974291[0] Operant conditioning of cortical unit activity

  • (Abstract) The activity of single neurons in precentral cortex of unanesthetized monkeys (Macaca mulatta) was conditioned by reinforcing high rates of neuronal discharge with delivery of a food pellet. Auditory or visual feedback of unit firing rates was usually provided in addition to food reinforcement. After several training sessions, monkeys could increase the activity of newly isolated cells by 50 to 500 percent above rates before reinforcement.
  • Used 'classical' single unit recording.
  • Trepination 5mm circle over hand area.
  • feedback: click for each AP.
  • reinforced on neuron per day.
  • trained neural activity often bursts, usually involved movement such as flexion of the lebow or rotation of the wrist.
  • controlled for sensory positive-feedback loop by performing extinction trials & looking for PETH response to click.
  • I gotta get one of these pellet feeders. monkeys will likely be more motivated, especially if I titrate how frequently they get the food.
  • images/303_1.pdf

PMID-5000088[1] Operant conditioning of specific patterns of neural and muscular activity.

In awake monkeys we recorded activity of single "motor" cortex cells, four contralateral arm muscles, and elbow position, while operantly reinforcing several patterns of motor activity. With the monkey's arm held semiprone in a cast hinged at the elbow, we reinforced active elbow movements and tested cell responses to passive elbow movements. With the cast immobilized we reinforced isometric contraction of each of the four muscles in isolation, and bursts of cortical cell activity with and without simultaneous suppression of muscle activity. Correlations between a precentral cell and specific arm muscles consistently appeared under several behavioral conditions, but could be dissociated by reinforcing cell activity and muscle suppression.

PMID-4624487[2] Operant conditioning of isolated activity in specific muscles and precentral cells

Recorded precentral units in monkeys, trained to contract 4 arm muscles in isolation, under various conditions: passive movements and cutaneous stimulation, active movements and isometric contractions. Some Ss were also reinforced for activity of cortical cells, with no contingency in muscle activity and with simultaneous suppression of all muscular activity. It is concluded that temporal correlations between activity of precentral cells and some other component of the motor response, e.g., muscle activity, force, or position, may depend as strongly on the specific response pattern which is reinforced as on any underlying physiological connection.

____References____

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ref: Najafi-1985.07 tags: Najafi original silicon michigan recording array 1985 MEA date: 01-06-2012 05:27 gmt revision:10 [9] [8] [7] [6] [5] [4] [head]

IEEE-1484848 (pdf) A high-yield IC-compatible multielectrode recording array.

  • Already talks about closed-loop control of a neuroprosthesis.
  • Started testing on-chip NMOS amplifiers.
  • tantalum and polysilicon conductors. some resistivity, but much less than the electrode interface.

____References____

Najafi, K. and Wise, K.D. and Mochizuki, T. A high-yield IC-compatible multichannel recording array Electron Devices, IEEE Transactions on 32 7 1206 - 1211 (1985)

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ref: Olds-1967.01 tags: Olds 1967 limbic system operant conditioning recording rats electrophysiology BMI date: 01-06-2012 03:59 gmt revision:2 [1] [0] [head]

PMID-6077726[0] The limbic system and behavioral reinforcement

  • Can't seem to find Olds 1965, as was a conference proceeding .. this will have to do, despite the lack of figures. images/966_1.pdf
  • First reference I can find of chronic (several weeks) (4-9 microelectrodes, single) recording from the rat.
  • Basically modern methods: commutator + solid state preamplifiers mounted to a counterbalanced slack-relieving arm.
    • If unit responses were observed in recordings from a given probe a week after surgery they were usually recordable indefinitely. 44 years later ...
  • Used a primitive but effective analog spike discriminator based on:
    • minimum amplitude
    • maximum amplitude
    • minimum fall time
    • maximum fall time.
  • Also had a head movement artifact detector, which blanked the recordings (stopped the paper roll) for 2 sec.
  • Reinforced on 'bursting', threshold sufficiently high that it only occurred once every 5-15 minutes.
  • Food reinforcement or 1/4 second train of brain stimulation (30ua, 60Hz, sine, in hypothalamus).
  • Reinforcement was conditioned on an 'acquisition' signal, which is visual (?) Bursting is rewarded for 2 minutes, ignored for 8 minutes.
  • Also recorded control neurons.
  • (they were looking at these things as though anew!) "The most striking aspect of the records so formed [on sheets of paper] was that all discriminators at one time or another exhibited rate changes that had the appearance of waves with a period of 10 to 20 minutes. Waves between units in the same animal were to some degree synchronized." Then describes a ramp ..
  • Longer term variations: FR would vary by a factor of 2-5 over a period of several hours.
    • This would make negatively correlated neurons (on a short time scale) appear positively correlated over long time scales (have to fix this in the BMI!)
  • As this was a conditional reinforcement task, they unexpectedly found that the acquisition periods were systematically different than extinction periods
    • More like pavlovian conditioning, esp in the hippocampus, where a conditioned response was also reflected on a control neuron.
    • Even when the light was lit throughout the acquisition period was replaced by a bell at the beginning of the acq. period, there was still a sustained change in FR.
      • Then during the extinction period: it appeared from the record of responses that a definite operant behavior was tried several times and then stopped altogether."
  • In the pontine nucleus (relay from M1 to cerebellum, v. roughly), judging from the control responses, all were conditioned.
    • Pontine responses seem to correspond with movement of the eyes or head that did not set off the movement detector/blanker.
  • Saw brief and very fast bursts during the extinction periods of the kind that Evarts found to characterize pyramical neurons during sleep.
  • When units shifted from food reward to ICS reward, units became undiffarentiated, and within a day they would be reconditioned.
  • Also tried paralyzing the animal to see if it could still generate operant responses; the animal died, results inconclusive.
  • Flood lights made it hard for the rats to produce the operant behavior.

____References____

[0] Olds J, The limbic system and behavioral reinforcement.Prog Brain Res 27no Issue 144-64 (1967)

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ref: notes-0 tags: clementine operant conditioning 041707 pyramidal tract tlh24 date: 01-06-2012 03:12 gmt revision:4 [3] [2] [1] [0] [head]

It appears that operant/feedback training of one neuron (channel 29, in SMA region) works fine (not great, but fine). In the experiment performed prior to visiting Seattle, on April 10 2007, I was not convinced that the neuron was controlling anything. Now, it is apparent that the monkey has some clue as to what he is doing. Today I made a simple change: I made the filtering function sum (all spikes) 1/12 * x*(x-1)^2, where x = time - time_of_spike. In comparison to a butterworth filter, this has no rebound oscillation & makes the estimation of firing rate much more transparent. It averages over approximately 500ms ~= lowcut of 1.5hz? I see no reason to change this filtering function much, as it works fine. Spikes were binned at 100hz as input to this function, but that should be equivalent to binning at 1khz etc.

Next time, i want to do 2d, where channel 62 controls the Y-axis. really should try to determine the approximate tunings of these cells. I'm somewhat concerned as this channel seems to have a much lower mean firing rate than channel 29. According to the literature, PTNs have high firing rates and strong tuning...

for reference, here is the channel used for the one-neuron BMI, recorded April 10. It has not changed much in the last 7 days.

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ref: bookmark-0 tags: neuroengineering blog date: 01-06-2012 03:10 gmt revision:1 [0] [head]

http://infinite-interface.net/ -- a neuroscientist at University of Southern California. Many thoughtful, informative posts.

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ref: thesis-0 tags: clementine 051607 operant conditioning tlh24 date: 01-06-2012 03:09 gmt revision:1 [0] [head]

the cells were, basically, as usual for today. did 1-d BMI on channel 29; worked somewhat (nothing dramatic; mk is out of practice?)

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ref: bookmark-2007.08 tags: donoghue cyberkinetics BMI braingate date: 01-06-2012 03:09 gmt revision:3 [2] [1] [0] [head]

images/425_1.pdf August 2007

  • provides more extensive details on the braingate system.
  • including, their automatic impedance tester (5mv, 10pa)
  • and the automatic spike sorter.
  • the different tests that were required, such as accelerated aging in 50-70 deg C saline baths
  • the long path to market - $30 - $40 million more (of course, they have since abandoned the product).

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ref: notes-2000.09 tags: BMI recording technology Chapin Nicolelis battery Wolf date: 01-06-2012 03:09 gmt revision:4 [3] [2] [1] [0] [head]

from the book "Neural Prostheses for Restoration of Sensory and Motor Function" edited by John Chapin and Karen Moxon.

Phillip Kennedy's one-channel neurotrophic glass electrode BMI (axons apparently grew into the electrode, and he recorded from them)

Pat Wolf on neural amplification / telemetry technology

battery technology for powering the neural telemetry

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ref: thesis-0 tags: clementine 042007 operant conditioning biofeedback tlh24 date: 01-06-2012 03:08 gmt revision:4 [3] [2] [1] [0] [head]

channel 29 controlled the X direction:

channel 81, the Y direction (this one was very highly modulated, and the monkey could get to a high rate ~60Hz. note that both units are sorted as one -- I ought to do the same on the other channels from now on, as this was rather predictive (this is duplicating Debbie Won's results):

However, when I ran a wiener filter on the binned spike rates (this is not the rates as estimated through the polynomial filter), ch 81 was most predictive for target X position; ch 29, Y target position (?). This is in agreement with population-wide predictions of target position: target X was predicted with low fidelity (1.12; cc = 0.35 or so); target Y was, apparently, unpredicted. I don't understand why this is, as I trained the monkey for 1/2 hour on just the opposite. Actually this is because the targets were not in a random sequence - they were in a CCW sequence, hence the neuronal activity was correlated to the last target, hence ch 81 to target X!

for reference, here is the ouput of bmi_sql:

order of columns: unit,channel, lag, snr, variable

ans =

    1.0000   80.0000    5.0000    1.0909    7.0000
    1.0000   80.0000    4.0000    1.0705    7.0000
    1.0000   80.0000    3.0000    1.0575    7.0000
    1.0000   80.0000    2.0000    1.0485    7.0000
    1.0000   80.0000    1.0000    1.0402    7.0000
    1.0000   28.0000    4.0000    1.0318    8.0000
    1.0000   76.0000    2.0000    1.0238   11.0000
    1.0000   76.0000    5.0000    1.0225   11.0000
    1.0000   17.0000         0    1.0209   11.0000
    1.0000   63.0000    3.0000    1.0202    8.0000

movies of the performance are here:

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ref: thesis-0 tags: clementine 042107 operant conditioning tlh24 date: 01-06-2012 03:08 gmt revision:5 [4] [3] [2] [1] [0] [head]

I tried to train Clem, once again, to do 2d BMI, this time with channel 69 for X and channel 71 for Y. X worked rather well, to a point - he realized that he could control it with left shoulder contractions, and did so (did not get a video of this). I did, however, get a video of the game, which is here:

Y training/performance was abysmal and hence did not try 2D control. Channel 71 would become silent whenever he began to pay attention; I'm not sure why. It would fire vigorously when he turned around and rested; the unit had a high firing rate at rest. I did not get a pic of the sortclient for today, but ch 29 was there as usual (though i did not use it) & channel 71 had the characteristic sharp V shape; perhaps it was an interneuron?? I don't know.

anyway, the data is in SQL on hardm.ath.cx. (the real proof is in the pudding, of course).

we really need to put the BMI game in his home cage, so motivation is not such a large issue

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ref: notes-0 tags: sorting SNR correlation coefficient expectation maximization tlh24 date: 01-06-2012 03:07 gmt revision:5 [4] [3] [2] [1] [0] [head]

Description: red is the per-channel cross-validated correlation coeifficent of prediction. Blue is the corresponding number of clusters that the unit was sorted into, divided by 10 to fit on the same axis. The variable being predicted is cartesian X position. note 32 channels were dead (from PP). The last four (most rpedictive) channels were: 71 (1 unit), 64 (5 units), 73 (6 units), 67 (1 unit). data from sql entry: clem 2007-03-08 18:59:27 timarm_log_20070308_185706.out ;Looks like this data came from PMD region.

Description: same as above, but for the y-axis.

Description: same as above, but for the z-axis.

Conclusion: sorting seems to matter & have a non-negligible positive effect on predictive ability.

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ref: BMI notes-0 tags: spike filtering rate_estimation BME 265 Henriquez date: 01-06-2012 03:06 gmt revision:1 [0] [head]

http://hardm.ath.cx:88/pdf/BME265_final.pdf

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ref: Towe-2007.05 tags: RF recording passive backscatter variactors date: 01-06-2012 02:56 gmt revision:3 [2] [1] [0] [head]

IEEE-4227238 (pdf) Passive Backscatter Biotelemetry for Neural Interfacing

  • ahaha. Someone else had the same idea, about at the same time. And they got it to work!

IEEE-5993487 (pdf) A Fully Passive Wireless Microsystem for Recording of Neuropotentials Using RF Backscattering Methods

  • Still not that sensitive -- about an order of magnitude too coarse.
  • Also, no multiplexing.
  • But: there is room, I think this technology has potential.
  • range only 1.5cm.
  • suggest performance can be improved by increasing the nonlinearity of the variactors.
  • Other papers by the author feature ultrasound-powered microstimulation. He's clearly into alternative approaches.

____References____

Towe, B.C. Neural Engineering, 2007. CNE '07. 3rd International IEEE/EMBS Conference on 144 -147 (2007)

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ref: Dethier-2011.28 tags: BMI decoder spiking neural network Kalman date: 01-06-2012 00:20 gmt revision:1 [0] [head]

IEEE-5910570 (pdf) Spiking neural network decoder for brain-machine interfaces

  • Golden standard: kalman filter.
  • Spiking neural network got within 1% of this standard.
  • THe 'neuromorphic' approach.
  • Used Nengo, freely available neural simulator.

____References____

Dethier, J. and Gilja, V. and Nuyujukian, P. and Elassaad, S.A. and Shenoy, K.V. and Boahen, K. Neural Engineering (NER), 2011 5th International IEEE/EMBS Conference on 396 -399 (2011)

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ref: tlh24-2011 tags: motor learning models BMI date: 01-06-2012 00:19 gmt revision:1 [0] [head]

Experiment: you have a key. You want that key to learn to control a BMI, but you do not want the BMI to learn how the key does things, as

  1. That is not applicable for when you don't have training data - amputees, parapalegics.
  2. That does not tell much about motor learning, which is what we are interested in.

Given this, I propose a very simple groupweight: one axis is controlled by the summed action of a certain population of neurons, the other by a second, disjoint, population; a third population serves as control. The task of the key is to figure out what does what: how does the firing of a given unit translate to movement (forward model). Then the task during actual behavior is to invert this: given movement end, what sequence of firings should be generated? I assume, for now, that the brain has inbuilt mechanisms for inverting models (not that it isn't incredibly interesting -- and I'll venture a guess that it's related to replay, perhaps backwards replay of events). This leaves us with the task of inferring the tool-model from behavior, a task that can be done now with our modern (though here-mentioned quite simple) machine learning algorithms. Specifically, it can be done through supervised learning: we know the input (neural firing rates) and the output (cursor motion), and need to learn the transform between them. I can think of many ways of doing this on a computer:

  1. Linear regression -- This is obvious given the problem statement and knowledge that the model is inherently linear and separable (no multiplication factors between the input vectors). n matlab, you'd just do mldivide (backslash opeartor) -- but but! this requires storing all behavior to date. Does the brain do this? I doubt it, but this model, for a linear BMI, is optimal. (You could extend it to be Bayesian if you want confidence intervals -- but this won't make it faster).
  2. Gradient descent -- During online performance, you (or the brain) adjusts the estimates of the weights per neuron to minimize error between observed behavior and estimated behavior (the estimated behavior would constitute a forward model..) This is just LMS; it works, but has a exponential convergence and may get stuck in local minima. This model will make predictions on which neurons change relevance in the behavior (more needed for acquiring reward) based on continuous-time updates.
  3. Batched Gradient descent -- Hypothetically, one could bolster the learning rate by running batches of data multiple times through a gradient descent algorithm. The brain very well could offline (sleep), and we can observe this. Such a mechanism would improve performance after sleep, which has been observed behaviorally in people (and primates?).
  4. Gated Gradient Descent -- This is halfway between reinforcement learning and gradient descent. Basically, the brain only updates weights when something of motivational / sensory salience occurs, e.g. juice reward. It differs from raw reinforcement learning in that there is still multiplication between sensory and motor data + subsequent derivative.
  5. Reinforcement learning -- Neurons are 'rewarded' at the instant juice is delivered; they adjust their behavior based on behavioral context (a target), which presumably (given how long we train our keys), is present in the brain at the same time the cursor enters the target. Sensory data and model-building are largely absent.

{i need to think more about model-building, model inversion, and songbird learning?}

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ref: Velliste-2008.06 tags: Schwartz 2008 Velliste BMI feeding population vector date: 01-06-2012 00:19 gmt revision:1 [0] [head]

PMID-18509337[0] Cortical control of a prosthetic arm for self-feeding

  • Idea: move BMI into robotic control.
  • population vector control, which has been shown to be inferior to the Wiener filter.
  • 112 units for control in one monkey. 2 monkeys used.
  • 4D control -- x, y, z, gripper.
  • 1064 trials over 13 days, average success rate of 78%
  • Gripper opened as the arm returned to mouth. Works b/c marshmallows are sticky.

____References____

[0] Velliste M, Perel S, Spalding MC, Whitford AS, Schwartz AB, Cortical control of a prosthetic arm for self-feeding.Nature 453:7198, 1098-101 (2008 Jun 19)

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ref: Peikon-2009.06 tags: Peikon Fitzsimmons Nicolelis video tracking walking BMI Idoya date: 01-06-2012 00:19 gmt revision:2 [1] [0] [head]

PMID-19464514[0] Three-dimensional, automated, real-time video system for tracking limb motion in brain-machine interface studies.

  • yepp.

____References____

[0] Peikon ID, Fitzsimmons NA, Lebedev MA, Nicolelis MA, Three-dimensional, automated, real-time video system for tracking limb motion in brain-machine interface studies.J Neurosci Methods 180:2, 224-33 (2009 Jun 15)

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ref: Brown-2007 tags: Kalman filter BMI Black spike_sorting Donoghue date: 01-06-2012 00:07 gmt revision:1 [0] [head]

From Uncertain Spikes to Prosthetic Control a powerpoint presentation w/ good overview of all that the Brown group has done

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ref: Porada-2000.01 tags: electrodes recording oblique inverted MEA arrays Kruger date: 01-05-2012 23:07 gmt revision:3 [2] [1] [0] [head]

PMID-10776811[0] More than a year of recording with up to 64 microelectrodes

  • for more than a year action potentials of good quality were obtained from most electrodes!
  • used 60mm-long, 12.5um Ni-Cr-Al (Isaohm) wire, polyimide insulated, soldered to microconnectors. Tips purely ('primitively') cut after bonding them to a piece of photographic film substrate.
  • implanted in the rabbit and marmoset V1 cortex from afar.
  • with the 8 rabbits they used a magnetic release to prevent excessive force from removing the implant.
  • used small sections of thicker wire to individually label the electrodes for x-ray; thusly could reconstruct the electrode positions. electrodes in the white matter were silent mais or menos.
  • the autocorrelation functions of the neurons generally look good; some of them do not have a refractory period though.
  • in GFAP-stained sections a single electrode track appeared as a hole of about 28 um wide. The outer diameter of the wire insulation as 18um. electrode tracts were not visible in cresyl violet tracts. the neurones near the electrode tips appeared normal.
  • we recorded signals for up to 711 days, during which time the recording quality did not degrade. nice, nice!
  • they think that the large length of free wire, running about 5mm through the brain provides a sufficient degree of friction so that locally the tissue is prevented from moving relative to the electrodes. They did not need to use microstimulation to improve recording quality.

____References____

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ref: Kelly-2007.01 tags: MEA single electrode comparison CMU Utah date: 01-05-2012 22:07 gmt revision:1 [0] [head]

PMID-17215384[0] Comparison of recordings from microelectrode arrays and single electrodes in the visual cortex.

  • We found that the array yields good recordings on a large number of electrodes, with qualities comparable to those from single electrode recordings. On average, the recording quality is somewhat lower than that of single electrodes, but nonetheless is sufficient for assessing tuning properties such as the spatiotemporal receptive field and orientation tuning.

____References____

[0] Kelly RC, Smith MA, Samonds JM, Kohn A, Bonds AB, Movshon JA, Lee TS, Comparison of recordings from microelectrode arrays and single electrodes in the visual cortex.J Neurosci 27:2, 261-4 (2007 Jan 10)

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ref: QingBai and Wise-2001.08 tags: Bai Wise buffered MEA recording electrodes Michigan date: 01-05-2012 04:53 gmt revision:5 [4] [3] [2] [1] [0] [head]

IEEE-936367 (pdf) Single-unit neural recording with active microelectrode arrays

  • Design neural probes with on-chip unity-gain amplifiers. Proven to not degrade recordings (indeed, it should help!)
  • 200ohm output impedance
  • 11uV RMS noise, 100Hz-10kHz.
  • Multiplexer adds 8uV rms noise. noise from clock transitions 2ppm.
  • Also built amplifiers with 40db voltage gain (100x).

____References____

Qing Bai and Wise, K.D. Single-unit neural recording with active microelectrode arrays Biomedical Engineering, IEEE Transactions on 48 8 911 -920 (2001)

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ref: Najafi-1986.12 tags: Najafi implantable wired recording Michigan array multiplexing silicon boron MEA date: 01-05-2012 03:07 gmt revision:8 [7] [6] [5] [4] [3] [2] [head]

IEEE-1052646 (pdf) An implantable multielectrode array with on-chip signal processing

  • "The major reason for the slow progress in the understanding of neural circuits has been the lack of adequate instrumentation."
  • previous photolithographic: [4],[5]. Their first publication: [7].
  • Kensall Wise, not Stephen.
  • Single shank
  • 10 recording sites spaced at 100um
  • Amplifying 100x, b/w 15kHz., multiplexing.
  • width: 15um near tip, 160um at base.
  • 3 leads (!) power, ground, data.
  • 6um LOCOS enhancement and depletion NMOS technology -- not CMOS. (latter is prone to latch-up)
  • 5mW power.
  • boron dope silicon, etch back non doped portion with ethylenediamine-pyrocatechol (EDP) water solution.
  • must not have any substrate bias!

____References____

Najafi, K. and Wise, K.D. An implantable multielectrode array with on-chip signal processing Solid-State Circuits, IEEE Journal of 21 6 1035 - 1044 (1986)

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ref: BASMAJIAN-1963.08 tags: original BMI M1 human EMG tuning operant control Basmajian date: 01-05-2012 00:49 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

PMID-13969854[0] Control and Training of Individual Motor Units

  • humans have the ability to control the firing rate of peripheral motor units with a high resolution.
  • "The quality of control over anterior horn cells may determine the rates of learning" yup!
  • "Some learn such esquisite control that they soon can produce rhythms of contraction in one unit, imitating drum rolls etc"
  • the youngest persons were among both the best and worst learners.
  • after about 30 minutes the subject was required to learn how to repress the first unit and to recruit another one.
    • motor unit = anterior horn cell, its axon, and all the muscle fibers on which the terminal branches of the axon end. max rate ~= 50hz.
    • motor units can be discriminated, much like cortical neurons, by their shape.
    • some patients could recruit 3-5 units altogether - from one bipolar electrode!
      • in playback mode (task: trigger the queried unit), several subjects had particular difficulty in recruiting the asked-for units. "They groped around in their conscious efforts to find them sometimes, it seemed, only succeded by accident"
    • some patients could recruit motor units in the absence of feedback, but they were unable to explain how they do it.
  • 0.025 (25um) nylon-insulated Karma alloy EMG recording wire.
  • feedback: auditory & visual (oscilloscope).
  • motor units have a maximum rate, above which overflow takes place and other units are recruited (in accord with the size principle).
  • "The controls (are) learned so quickly, are so esquisite, are so well retained after the feedbacks are eliminated that one must not dismiss them as tricks"

____References____

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ref: Wyler-1974.02 tags: Wyler Fetz BMI operant conditioning date: 01-05-2012 00:46 gmt revision:3 [2] [1] [0] [head]

PMID-4207598[0] Behavioral control of firing patterns of normal and abnormal neurons in chronic epileptic cortex.

  • Idea: epilepsy treated through biofeedback.
  • Induced epilepsy in monkeys via alumina.
  • Conditioned 198 cells in epileptiform focus; 107 had normal firing patterns.
  • 91 cells had abnormal patterns:
    • Structured bursts with high, invariant burst indices, and could not be conditioned.
    • Cells did not change burstyness based on behavioral state.
    • Lower and more variable burst indices and were as easily conditioned as normal cells.
      • These cells bursted more when the monkey was not paying attention.
  • Operant control: ref 8, 9.
  • Ach, fascinating:
  • Normal precentral cells rarely exhibited interspike intervals less than 10 msec, except during vigorous movements or sleep.
  • Neurons were deemed 'bursty' if they exhibited spontaneous high-frequency firing with interspike intervals less that 5msec.
  • Monkeys obtained proficiency with high-frequency conditioning more quickly and effectively than with low-freq, even with 40% on high and 60% on low.
  • All conditioned cells corresponded to some movement of the contralateral arm (again).
  • Operant conditioning is interesting in this case, as it indicates if cells are still 'functional' in the ensemble.
  • See also: PMID-809116[1]

____References____

[0] Wyler AR, Fetz EE, Behavioral control of firing patterns of normal and abnormal neurons in chronic epileptic cortex.Exp Neurol 42:2, 448-64 (1974 Feb)
[1] Wyler AR, Fetz EE, Ward AA Jr, Firing patterns of epileptic and normal neurons in the chronic alumina focus in undrugged monkeys during different behavioral states.Brain Res 98:1, 1-20 (1975 Nov 7)

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ref: Lilly-1958 tags: Lilly MEA original neural tuning date: 01-04-2012 02:15 gmt revision:4 [3] [2] [1] [0] [head]

bibtex: Lilly-1958 Correlations between Neurophysiological Activity in the Cortex and Short-Term Behavior in the Monkey

  • 610 channels in 'Susie'! Unable to record from all of them for lack of recording technology.
  • references the rest of his work.
  • Was able to elicit pretty dramatic and fascinating stimulation responses:
    • 'shrink' as if warding off a blow to the contralateral side of the head;
    • at an adjacent electrode we found a pattern called 'goose', this pattern involved the whole body, and the reaction looks as if the monkey had been forcefully, mechanically stimulated par anum.
    • both were accompanied by high arousal.
  • Suggest that behavioral frequency-of-use corresponds rounghly to cortical rank-area order.
  • Note that the wave velocity (as imaged by his bavatron) in cortex can vary dramatically, from 1 m/sec to 0.1 m/sec.
    • With practice, one can see the boundaries between the 'arm' and 'leg' regions quite easily.
  • Stated our problem quite concisely: "One of the large difficulties in correlating structure, behavior, and CNS activity is the spatial problem of getting enough electrodes, and small enough electrodes, \emph{in} there with minimal injury. (This is why he was usnig pial electrodes). Still another problem is getting enough samples from each electrode per unit time, over a long enough time, to see what goes on during conditioning or learning [...] s for the problem of the investigator's absorbing the data -- if he has adequate recording techniques, he has a lot of time to work on a very short recorded part of a given monkey's life."
  • no figures :-(
  • Lilly could publish. a b -- though he appears to have ADHD (perhaps from the LSD)
    • also see his homepage -- He died in 2001, but it's still up.
  • images/1016_1.pdf

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ref: Nicolelis-2003.09 tags: nicolelis recording electrode monkeys MEA date: 01-04-2012 01:23 gmt revision:3 [2] [1] [0] [head]

PMID-12960378 Chronic, multisite, multielectrode recordings in macaque monkeys.

  • max 412 neurons, snr 5
  • up to 18 months, with precipitous decline
  • Miguel is the first author. well, that only makes sense.

____References____

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ref: Goldstein-1973.07 tags: Salcman microelectrodes bucking analysis stiffness youngs modulus mechanical MEA date: 01-04-2012 01:22 gmt revision:4 [3] [2] [1] [0] [head]

IEEE-4120642 (pdf) Mechanical Factors in the Design of Chronic Recording Intracortical Microelectrodes

____References____

Goldstein, Seth R. and Salcman, Michael Mechanical Factors in the Design of Chronic Recording Intracortical Microelectrodes Biomedical Engineering, IEEE Transactions on BME-20 4 260 -269 (1973)

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ref: Hubel-1957.03 tags: Hubel original tungsten electrode date: 01-03-2012 23:46 gmt revision:3 [2] [1] [0] [head]

PMID-17793797[0] Tungsten Microelectrode for Recording from Single Units.

  • Advancement upon the micropipette.
  • Lacquer insulation.
  • Suggest that 5um tips or smaller are the best for single unit recording.
  • Steel becomes too fragile near the tip of a very sharp point (what about steel blades?)
  • Electropolishing: immerse a few milimeters in KNO 2KNO_2 solution and apply 2-6V AC.
    • Such a result is explained by the fact that the meniscus height depends on the diameter of the wire, which decreases as the polishing proceeds.
  • 75M resistance (!!); 500k to 5M at 5-10kHz.
  • Note that he had been recording from at least 1959.

____References____

[0] Hubel DH, Tungsten Microelectrode for Recording from Single Units.Science 125:3247, 549-50 (1957 Mar 22)

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ref: Evarts-1969.05 tags: Evarts pyramidal tract motor control M1 tuning date: 01-03-2012 23:08 gmt revision:2 [1] [0] [head]

PMID-4977837[0] Activity of Pyramidal Tract neurons during postural fixation

  • Force was thus dissociated from displacement, and it was possible to determine whether PTN discharges were related to position or force.
  • for the majority of PTNs discharge frequency was related to to the magnitude and rate of change of force rather than to the joint position or the speed of joint movement (same as the MUA in the Kinarm data!!)
  • task was simple: just try to avoid joint movement.
  • in comparison to [1] where PTN were related to force under joint displacement, this task shows they are still related to force even when the joint angle is fixed.
  • used sharpened tungsten electrodes to record 102 pyramidal tract neurons.
  • monkeys were trained to do the tasks in their home cages (obviously weren't recorded there - need to be headposted)
  • I'm not sure how he determined if it was or was not a pyramidal tract neuron.

____References____

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ref: Fetz-2000.12 tags: motor control spinal neurons interneurons movement primitives Fetz review tuning date: 01-03-2012 23:08 gmt revision:4 [3] [2] [1] [0] [head]

PMID-11240278[0] Functions of mammalian spinal interneurons during movement

  • this issue of current opinion in neuro has many reviews of motor control
  • points out that the Bizzi results (they microstimulated & observed a force-field-primitive type organization)
    • others have found that this may be a consequence of decerebration + the structure of the biomechanical groupings of muscles. (see 'update').
  • intraspinal electrodes in the cat provide a secure and reliable method of eliciting forces and movements.
  • CM (corticomotor) cells more often represent synergistic groups of muscles, whereas premotor spinal interneurons are organized to target specific muscles.
    • CMs are therefore more strictly recruited for particular movements.
  • interneurons (IN) are, of course, arrayed in such a way so that antagonist and agonist muscles cross-inhibit eachother (for efficiency)
    • however, we are still able to control the endpoint impedance of the arm - how?
  • spinal interneurons modulate activity during wait period prior to movement!
    • there might be substantial interaction between the cortex and spinal cord.. subjects asked to imagine pressing a foot pedal showed enhanced reflexes in the involved soleus muscle.
      • cognitive priming?
  • spinal reflexes are strongly modulated in movement.

____References____

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ref: Sodagar-2007.06 tags: neural recording telemetry Wise Najafi mulitichannel electrophysiology Michigan ASIC date: 01-03-2012 23:07 gmt revision:4 [3] [2] [1] [0] [head]

PMID-17554826[0] A fully integrated mixed-signal neural processor for implantable multichannel cortical recording.

  • document is rich in details! looks pretty well designed, too.
  • Michigan 3-d electrodes
  • inductively powered, 2Mbps output
  • 64 channels
  • 18b/spike for 64 channels in scan mode, continuous waveforms on 2 channels in monitor mode
  • programmable analog spike detection. resolution: 5 bits.
  • no timestamps - send them out as they come in, with a clock rate fast enough so that this does not matter.
    • temporary storage in SRAM
    • time compression and buffering is somewhat complex (?)
  • only transmit threshold crossings, positive, negative, and both.
    • they do not detail how the signal is telemetered - perhaps this is for another publication.
  • fabricated chip occupies 3.5 x 2.7 mm. 0.5um process.
  • fabricated chip has a power of 200uw @ 1.8V. that's 6.4mW altogether! I need to get down to this figure! (well..)

____References____

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ref: Olson-2005 tags: Arizona rats BMI motor control training SVM single-unit left right closed-loop learning Olson Arizona date: 01-03-2012 23:06 gmt revision:1 [0] [head]

bibtex:Olson-2005 Evidence of a mechanism of neural adaptation in the closed loop control of directions

  • from abstract:
    • Trained rats to press left/right paddles to center a LED. e.g. paddles were arrow keys, LED was the cursor, which had to be centered. Smart rats.
      • Experiment & data from Olson 2005
    • Then trained a SVM to discriminate left/right from 2-10 motor units.
    • Once closed-loop BMI was established, monitored changes in the firing properties of the recorded neurons, specifically wrt the continually(?) re-adapted decoding SVM.
    • "but expect that the patients who use the devices will adapt to the devices using single neuron modulation changes. " --v. interesting!
  • First page of article has an excellent review back to Fetz and Schmidt. e.g. {303}
  • Excellent review of history altogether.
    • Notable is their interpretation of Sanchez 2004 {259}, who showed that most of the significant modulations are from a small group of neurons, not the large (up to 320 electrodes) populations that were actually recorded. Carmena 2003 showed that the population as a whole tended to group tuning, although this was imperfectly controlled.
  • Also reviewed: Zacksenhouse 2007 {901}
  • SVM is particularly interesting as a decoding algorithm as it weights the input vectors in projecting onto a decision boundary; these weights are experimentally informative.
  • Figure 7: The brain seems to modulate individual firing rate changes to move away from the decision boundary, or at least to minimize overlap.
  • For non-overt movements, the distance from decision function was greater than for overt movements.
  • Rho ( ρ\rho ) is the Mann-Whitney test statistic, which non-parametrically estimates the difference between two distributions.
  • δf(X t)\delta f(X_t) is the gradient wrt the p input dimensions o9f the NAV, as defined with their gaussian kernel SVM.
  • They show (i guess) that changes in ρ\rho are correlated with the gradient -- e.g. the brain focuses on neurons that increase fidelity of control?
    • But how does the brain figure this out??
  • Not sure if i fully understand their argument / support.
  • Conclusion comes early in the paper
    • figure 5 weakly supports the single-neuron modulation result.

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ref: Najafi-1990.05 tags: Najafi Michigan probe silicon strength electrodes recording MEA date: 01-03-2012 22:45 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-2345003[0] Strength characterization of silicon microprobes in neurophysiological tissues.

  • These active (with amplification/buffering circuitry) electrodes were around since 1990! It's been a while, and at least the devices are commercially available now.
  • Show that thin-film silicon is remarkably flexible and tough - about six times as strong as bulk silicon.
  • Have developed a silicon probe with an integrated phosphorous-doped polysilicon strain guague - nice.

____References____

[0] Najafi K, Hetke JF, Strength characterization of silicon microprobes in neurophysiological tissues.IEEE Trans Biomed Eng 37:5, 474-81 (1990 May)

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ref: GULD-1964.07 tags: platinum iridium microelectrode eltrolytic etching original date: 01-03-2012 19:05 gmt revision:2 [1] [0] [head]

PMID-14199966[0] A Glass-covered platinum microelectrode

  • Details the manufacture and testing of PT-IR (70/30) etched solder glass-coated microelectrodes.
  • Melt a bead of the glass on the top and gradually draw the bead downward, surrounded by the heater of a pipette drawing machine.

____References____

[0] GULD C, A GLASS-COVERED PLATINUM MICROELECTRODE.Med Electron Biol Eng 2no Issue 317-27 (1964 Jul)

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ref: Tian-2010.08 tags: nanowire nanoprobe silicon FET doping cis trans extracellular intracellular recording neuro MEA date: 01-03-2012 16:35 gmt revision:4 [3] [2] [1] [0] [head]

PMID-20705858[0] Three-Dimensional, Flexible Nanoscale Field-Effect Transistors as Localized Bioprobes

  • Made a silicon nanowire with 60 deg. kinks via trans/cis manipulation.
  • Doped one part of the N nanowire P to make a 200nm long FET whose gate is simply the surface of the nanowire (I think, have to check the refs)
  • Attached the nanoprobe / nanowire to flexible PMMA / SM-8 support which, due to interfacial stress, rose off the substrate (clever!)
  • Coated tip with phospholipid layers -> better cell attachment / penetration.
    • Possible to have the cell pull the nanoprobe in via endocytic pathways.
  • Were able to record intracellular and extracellular AP from rabbit cardiocytes. (!!!)

____References____

[0] Tian B, Cohen-Karni T, Qing Q, Duan X, Xie P, Lieber CM, Three-dimensional, flexible nanoscale field-effect transistors as localized bioprobes.Science 329:5993, 830-4 (2010 Aug 13)

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ref: Dabrowski-2003.1 tags: ASIC neural recording poland neuroplat pseudoresistor date: 01-03-2012 15:24 gmt revision:4 [3] [2] [1] [0] [head]

IEEE-1351853 (pdf) Development of integrated circuits for readout of microelectrode arrays to image neuronal activity in live retinal tissue

  • Use miller effect to increas capacitance for HPF.
  • resistors are long channel PMOS 3um / 500um, biased in linear region @ 0V.
    • Transistors must be in linear region: implement gate following of input signal. By varying this gate voltage, can change the filter characteristics.
  • Amplifier looks rather clever.
  • 7uV RMS input-referred noise.

____References____

Dabrowski, W. and Grybos, P. and Hottowy, P. and Skoczen, A. and Swientek, K. and Bezayiff, N. and Grillo, A.A. and Kachiguine, S. and Litke, A.M. and Sher, A. Nuclear Science Symposium Conference Record, 2003 IEEE 2 956 - 960 Vol.2 (2003)

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ref: Bures-1968 tags: inferior colliculus stimulation classical conditioning plasticity hebb Bures date: 01-03-2012 07:08 gmt revision:5 [4] [3] [2] [1] [0] [head]

bibtex:Bures-1968 Plastic changes of unit activity based on reinforcing properties of extracellular stimulation of single neurons

  • images/972_1.pdf
  • Trained neurons to respond to auditory stimuli throughout the brain (though mostly the IC) to a auditory tone.
    • Hebb's rule, verified.
  • Yoshii & Ogura (22): Reticular units, originally not responding to sciatic nerve US, started to respond to the CS after a few tens of trials, however the conditioned reactions disappeared with continued training.
    • This must be regarded as response to arousal at the initial stages of classical aversive (sciatic nerve pain?) conditioning.
  • Used capilary electrodes 1um in diameter, filled with KCl or sodium glutamate
  • Stimulation current 10-50nA DC, 0.3-1 sec.
  • Were able to record and stimulate at the same time using these glass microelectrodes.
  • The majority of units (cortex, reticular formation, thalamus) showed no response, though some did. These responses tended to fade with overtraining.
  • Quote: "The rather low incidence of positive results int he above experiment might be due to the fact that many examined neurons lack even an indirect acoustic input and cannot, therefore, be activated by acoustic stimuli."
  • Neurons in the IC show the strongest plastic change.
  • Their study is more specific than Loucks (15), Olds and Milner (17) Delgaso (6) Doty(7) which used less specific ICMS.
  • That said, there is no behavior .. so we don't know if the stimuli is being reacted to or attended to (might explain the low # of responses in areas).
  • They also think that the response can be credited to nonspecific phenomena like dominant focus, reflex sensitization, or heterosynaptic facilitation.
    • That said, the IC did show strong responses.

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ref: Pearce-2004.01 tags: neural recording microfluidics in-vitro MEA date: 01-03-2012 06:53 gmt revision:4 [3] [2] [1] [0] [head]

PMID-17271187[0] Dynamic control of extracellular environment in in vitro neural recording systems.

  • they show how to create microfluidic channels on top of in-vitro microfluidic arrays.
  • used dorsal root ganglion cells.
  • key aspect:
    • make a thin cavity/space between two polycarbonate panes.
    • fill the cavity with liquid-phase isobornyl acrylate
    • cover the panes with a high-resolution mask
    • upon exposure to UV light the isobornyl polymerizes.
    • did this on top of a MEA-60
  • looks like they can very accurately deliver pulses and streams of fluid.

____References____

[0] Pearce T, Oakes S, Pope R, Williams J, Dynamic control of extracellular environment in in vitro neural recording systems.Conf Proc IEEE Eng Med Biol Soc 6no Issue 4045-8 (2004)

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ref: notes-0 tags: k-means clustering neurophysiology sorting date: 01-03-2012 06:51 gmt revision:1 [0] [head]

k-means is easy!

% i want to do the k-means alg. 
v = [x y]; 
nc = 7;
dim = cols(v); 
n = rows(v); 
cent = rand(nc,dim); 
d = zeros(n, nc); 
for k = (1:500)
	for s = 1:nc
		d(:,s) = sqrt(sum((v - rvecrep(cent(s, :), n)).^2,2));
	end
	% select the smallest
	[nada, g] = min(d'); 
	g = g';
	for s = 1:nc
		if(numel(find(g==s)) > 0)
			cent(s, :) = mean(v(g==s, :));
		end
	end
end

real data from clementine:

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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: Moran-1999.11 tags: electrophysiology motor cortex Schwartz Moran M1 tuning date: 01-03-2012 03:36 gmt revision:2 [1] [0] [head]

PMID-10561437[0] Motor cortical representation of speed and direction during reaching

  • velocity is represented in the motor cortex.
  • they developed an equation relating firing rate to the position and velocity.
  • EMG direction had significantly different tuning from the cortical activity
    • the effect of speed on EMG was also different.
  • used single-electrode recording - 1,066 cells!!
  • introduce the square-root transformation of the firing rate (from Ashe and Georgopolous 1994)

____References____

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ref: Fu-1993.11 tags: electrophysiology Ebner premotor motor tuning M1 date: 01-03-2012 03:34 gmt revision:1 [0] [head]

PMID-8294972 Neuronal specification of direction and distance during reaching movements in the superior precentral premotor area and primary motor cortex of monkeys. 1993

  • trained monkey to do center-out task, 48 targets (8 angles, 6 distances).
  • single-electrode recording of 197 neurons in the primary motor and secondary motor / premotor (in the superior precentral sulcus).
  • cells were mostly tuned to direction, and less to distance, in both the premovement and movement periods. distance tuning was much stronger in the movement period.
    • tuning was measure by average firing rate for the premovement, movement, and total periods.
  • long, very detailed!

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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: Blum-2007.12 tags: stimulation recording Blum integrated circuit ASIC date: 01-03-2012 03:26 gmt revision:8 [7] [6] [5] [4] [3] [2] [head]

IEEE-4358608 (pdf) An Integrated System for Simultaneous, Multichannel Neuronal Stimulation and Recording

  • Use capacitor-feedback amplifier with a seperate feedback amp to provide a DC path.
  • Input amplifier is disabled during stimulation (hopefully without blowing out gate oxide..)
  • Charge stored in the feedback caps acts as a S/H. clever!
  • Due to topology, noise increases with bias current of feedback amp.
  • Stimluation was a measly 9ua.
  • Use a feedback amplifier to actively discharge the electrode after stimulation.
  • Generally a well-though-out, informative paper, with insight as to the design compromises.

Blum RA, Ross JD Brown EA and DeWeerth SP (2007) An Integrated System for Simultaneous, Multichannel Neuronal Stimulation and Recording IEEE Trans. Circuits Syst. I. Regular Pap 54, 2608-2618

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ref: -0 tags: Evarts force pyramidal tract M1 movement monkeys conduction velocity tuning date: 01-03-2012 03:25 gmt revision:3 [2] [1] [0] [head]

PMID-4966614 Relation of pyramidal tract activity to force exerted during voluntary movement.

  • One of the pioneering studies of electrophysiology in awake behaving animals; single electrode juice reward headposting: many followed.
  • {960} looked at conduction velocity, which we largely ignore now -- most highly mylenated axons are silent during motor quiescence and show phasic activity during movement.
    • Lower conduction velocity PTNs show + and - FR modulations. Again from [5]
  • [6] showed that PTN activity preceded EMG activity, implying that it was efferent rather than afferent feedback that was controlling the fr. as expected.
  • task: wrist flexion & extension under load.
  • task in monkey's home cage for a period of three months; monkeys carried out 3000 trials or more of the task (must have had strong wrists!)
  • Head fixated the monkeys for about 10 days prior unit recordings; "The monkeys learned to be quite cooperative in reentering the chair in the morning, since entrance to the chair was rewarded by the fruit juice of their choice (grape, apple, or orange). Indeed, some monkeys continued to work even in the presence of free water!
    • Maybe I should give mango some Hawaiian punch as well?
  • Mesured antidromic responses with a permanent electrode in the ipsilateral medullary pyramid.
  • Used glass insulated platinum-iridium electrodes [11]
  • traces are clean, very clean. I wonder if good insulation (in this case, glass) has anything to do with it?
  • controlled for displacement by varying the direction of load; PTNs seem to directly control muscles.
    • Fire during acceleration and movement for no load
    • Fire during load and co-contraction when loaded.
  • FR also related to δF/δt\delta F / \delta t : FR higher during a low but rising force than a high but falling force.
  • more than 100 PTN recorded from the precentral gyrus, but only 31' had clear and consistent relation to performance on the task.
    • 16 units on extension loads, 7 units flexion loads
    • It was only one joint afterall..
  • Cells responding to the same movement (flexion or extension) were often founf on the same vertical electrode tract.
  • Very little response to joint position.
  • Very clean moculations -- neurons are almost silent if there is no force production; FR goes up to 50-80Hz.
  • Prior to the exp Evart expected a position tuning model, but saw clear evidence of force tuning.
  • Group 1 muscle afferents have now been shown to project to the motor cortex of both monkey [1] and cat [9]. Make sense, as if the ctx is to control force, it needs feedback regarding its production.
  • Caveats: many muscles were involved in the study, mainly due to postural effects, and having one or two controls poorly delineates what is going on in the motor ctx.
    • Plus, all the muscles controlling the figers come into play -- the manipulandum must be gripped firmly, esp to resist extension loads.

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ref: WISE-2004.01 tags: wireless electrodes silicon Michigan Kipke Najafi recording MEA date: 01-03-2012 03:23 gmt revision:12 [11] [10] [9] [8] [7] [6] [head]

IEEE-01258173 (pdf) Wireless implantable microsystems: high-density electronic interfaces to the nervous system - January 2004.

  • very impressive!
  • based on the old / well established beam-lead technology (see the image of the paper at the bottom of that page).
    • required 20 years of development to create an etching process with sufficient yield, though. Microprobes have been in development since 1966.
    • Silicon is slowly attacked by saline; however, the use of a boron etch-stop to define the substrate virtually eliminates such erosion.
    • Silicon dioxide is known to slowly hydrate in water, but this can be mitigated by CVD of silicon nitride / silicon oxide stacks. Polysilicon can be used too, since it forms a tight bond with silicon oxide, keeping water out.
      • Why don't they just seal it with a known impermeable plastic/epoxy/whatever? (They do, later) Utah probe is sealed in parylene.
    • Shunt capacitance is negligible compared to site capacitance; heavy substrate doping minimizes electrical or optically induced noise & virtually eliminates crosstalk.
    • (Of course) Silicon allows amplifiers and circuitry to be formed at/near the electrode, eliminating the need for (some) interconnects.
    • Silicon ribbon connectors cannot be made much longer than a few centimeters. 4um thick silicon cables are 100x more flexible than a 25um gold wire (!!) - but that is out-of-plane; they are relatively weak for in-plane stress.
  • Gold has a maximum charge delivery of 20uC/cm^2 ; platinum, 75 uC/cm^2 ; iridium oxide, 3000 uC/cm^2.
  • Glass can be hermetically bonded to silicon if both flat clean surfaces are put in opposition with a high voltage (1500V) placed across the interface at an elevated temperature (400C). These packages have been shown to be stable and inert in guinea pigs.
    • Silicon nitride, thin metal films, and metal films over polymers are all attractive coatings for probes (with no mention of biocompatibility); they last decades in salt water, and eventually succumb to pinholes.
  • Silicon probes outperform microwire arrays by a factor of (up to) 50 in terms of volume of tissue displaced / recording site. Michigan probes are typically 15um thick x 60um in cross section.
  • they tend to use many more recording sites than recording channels, hence, have a low expected yield. e.g. they have a 1024 site electrode (see the cool figures!), and can record from the best 128 of those. good idea, reasonable strategy, I guess.
    • they demonstrate that it is not too hard to remove the artifact of multiplexing on their systems - the multiplexing noise is below electrode noise.
  • talk about spongifying their iridium electrodes using current pulses in a PBS solution to (apparently) lower electrode impedance.
  • talk about drug delivery too
  • describe the exact manufacturing procedures that the Michigan arrays are created, including the critical back-etch (which i don't exactly understand).
  • describe the circuits used to amplify low-level neural signals.
  • Their charge-redistribution ADC is okay - 250ksps, 9b resolution, 1.4mW from a 3v source. Commercial ADCS are better - AD7467 is 0.6mw, 200ksps, 10bits. (though it scales up to 1.3mW @ 3V, 200ksps ; 0.36mW @1.8V - so the devices are comparable.)
  • some of the (very tiny) electrodes have 'holes' (!)
  • also have wireless microstimulators.
  • demonstrate long-term recording: 383days post implant in a rat & there are still many cells (though the figure is not that great, it is easy to understand) (this might be an exemplar)
  • associated website?
  • (quote:) "For ranges of a few centimeters, the high attenuation of RF signals in biological tissue dictates carrier frequencies below 10Mhz." Their solution is to use FSK with octave jumps in freqency & modulation rates up to 60% that of the carrier frequency.

____References____

WISE, K.D. and ANDERSON, D.J. and HETKE, J.F. and KIPKE, D.R. and NAJAFI, K. Wireless implantable microsystems: high-density electronic interfaces to the nervous system Proceedings of the IEEE 92 1 76 - 97 (2004)

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ref: Csicsvari-2003.08 tags: recording michigan silicon electrodes Buzsaki MEA date: 01-03-2012 03:23 gmt revision:4 [3] [2] [1] [0] [head]

PMID-12904510[0] Csicsvari 2003 Massively parallel recording of unit and local field potentials with silicon-based electrodes

  • What's so massive? 64 or 96 channel Michigan probes.
  • Motivation: recording local connections and interactions requires precise knoledge of the location of your recording sites.
  • Some classic refs on cortical building blocks.
  • Optical recording: Mao et al 2001 PMID-11738033.
  • Wired recording:, Chicurel 2001; Deadwyler and Hampson 1995 PMID-7481817; Evarts 1968; {994}
  • Tetrodes: Drake 1988, Gray 1995, McNaughton et al 1983; Recce and O'Keefe 1989.
  • on-chip active circuitry (simple voltage feedback op-amp - without reference electrodes!) reduces microphone artifact. 6mm 'antenna'.
    • refs: Bai and Wise 2001 {995}; Olsson et al. 2002
    • also Najafi and Wise 1986 {996}; Wise and Najafi 1991 .
  • Stored wideband data; sorted via KlustaKwik.
  • Total recording area 1.6mm deep by 1.8mm wide. Shanks separated by 300um ; recordings sites separated by 100um; shanks 12um thick.
    • Made via double-sided deep reactive reactive ion etching (DRIE).
  • stimulated the entorhinal cortex & recorded in the hippocampus; used the precise spatial layout of the micromachined silicon electrodes to map out the evoked potentials.
  • figure 3 shows that they can record the 'same' neuron from multiple 100um-spaced sites on a given shank. Some of this is due to the physically large extent of the hippocampal cells which they recorded; spike propagate both down the axon and back into the soma, and by using Current Source Density maps, they could estimate some of spatio-temporal characterisics of the AP.
    • CSD is the second spatial derivtive of the local field potentials.
    • Could measure forward and back-propagation of APs to the dendrites (!)
  • quote: in contrast to wire tetrodes with blunt cute ends, it was possible to record from the same cell layer numerous times after moving the probe up and subsequently back to the previous recording location.
    • size of the electrode shanks: 62um wide x 12um thick at top of recording site of 12 site shank; 82um wide at top of 16 site shank.
    • Top 4 recording sites' recording quality deteriorated with multiple penetrations.
  • good place-cell map; cells were discriminated based on a PCA across both time and electrode.

____References____

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ref: Delgado-1968.1 tags: Delgado wireless stimulation recording electrode date: 01-03-2012 03:22 gmt revision:3 [2] [1] [0] [head]

PMID-5683678[0] Intracerebral radio stimulation and recording in completely free patients.

  • images/978_1.pdf
  • See: The cordoba bull ranch experiment (youtube).
  • "This paper reports instrumentation used and clinical application in four patients with psychomotor epilepsy in whom electrodes had been implanted in the temporal lobes. To our knowledge, this is the first clinical use of intracerebral radio stimulation and recording in man. "
  • Electrode: 1.2mm plastic stylus, 15 stainless steel 3mm wide contacts attached at 3mm intervals.
  • Implanted in the anterior medial amygdala.
  • The receiver-stimulator which is carried by the subject, measures 3.7cm x 3.0cm x 1.4cm, and weighs 20g. The solid-state circuitry is encapsulated in epoxy resin which provides it with very good mechanical strength and makes it waterproof. Space for the 7-volt Mercury battery is included in the size mentioned above.
  • 3 channels stim, individual pulse intensity, same pulse duration and repetition for all 3 channels.
    • Operating range 100ft.
    • max current 2uA.
  • 216Mhz IRIG EEG transimtter, FM modulated.
    • The size of the three-channel unit, including the battery, is 4.5cm x 4.5cm x 1.5cm, and it weighs 50g.
    • Input-referred noise: 5uV.
  • Remarkable: one cerebral contact could be shared by recording and stimulating units. (2MOhm input impedance in the EEG amps)
  • Radio stimulation of different points in the amygdala and hippocampus in the four patients produced a variety of effects including pleasant sensations, elation, deep, thoughtful, concentration, odd feelings , super relaxation, colored visions, and other responses.
  • Extensive information has been published about different systems for radio telemetry in biological studies (Barwick & Fullagar, 1967; Caceres, 1965; Geddes, 1962; Slater, 1963). The disparity between the large number of technical papers and the few reports of results indicates the existence of methodological problems.
    • Recall that cardiac pacemakers were by this time in common use.

____References____

[0] Delgado JM, Mark V, Sweet W, Ervin F, Weiss G, Bach-Y-Rita G, Hagiwara R, Intracerebral radio stimulation and recording in completely free patients.J Nerv Ment Dis 147:4, 329-40 (1968 Oct)

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ref: Otto-2006.02 tags: electrophysiology recording rejuvenation stimulation MEA date: 01-03-2012 03:21 gmt revision:3 [2] [1] [0] [head]

PMID-16485763[0] Voltage pulses change neural interface properties and improve unit recordings with chronically implanted microelectrodes.

  • stimulation protocol: 1.5 volts, cortical electrode positive, 4 seconds, DC, current measured.
  • results: 10% mean improvement in SNR (not that great, oh well)
    • however, some effects were really profound: complete rejuvenation of the recordings!
  • result: 67% lower impedance.

____References____

[0] 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)

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ref: Kennedy-1989.09 tags: Kennedy neurotrophic electrode recording fabrication 1989 electrophysiology date: 01-03-2012 03:21 gmt revision:2 [1] [0] [head]

PMID-2796391[0] The cone electrode: a long-term electrode that records from neurites grown onto its recording surface.

  • A piece of the sciatic nerve is placed in the glass cone before implantation in the cortex of a rat.
  • A neurite can be an axon or dendrite.

____References____

[0] Kennedy PR, The cone electrode: a long-term electrode that records from neurites grown onto its recording surface.J Neurosci Methods 29:3, 181-93 (1989 Sep)

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ref: Williams-1999.12 tags: recording microwire guinea kipke MEA Michigan date: 01-03-2012 03:18 gmt revision:2 [1] [0] [head]

PMID-10592339[0] Long term neural recording characteristics of wire microelectrode arrays implanted in cerebral cortex

  • details the williams microwire array assembly protocol - basically the same as what gary does here in the nicolelis lab, only written up nicely and for guinea pigs not rhesus macaques.
  • references miguel's book on multielectrode recordings

____References____

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ref: Rolston-2009.01 tags: ICMS artifacts stimulation Rolston Potter recording BMI date: 01-03-2012 02:38 gmt revision:3 [2] [1] [0] [head]

PMID-19668698[0] A low-cost multielectrode system for data acquisition enabling real-time closed-loop processing with rapid recovery from stimulation artifacts

  • Well written, well tested, but fundamentally simple system - only two poles active high-pass, one pole low-pass.
  • With TBSI headstages the stimulation artifact is brief - figure 8 shows < 4ms.
  • Includes NeuroWriter software, generously open-sourced (but alas windows only - C#).

____References____

[0] Rolston JD, Gross RE, Potter SM, A low-cost multielectrode system for data acquisition enabling real-time closed-loop processing with rapid recovery from stimulation artifacts.Front Neuroengineering 2no Issue 12 (2009)

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ref: -0 tags: reinforcement learning basis function policy specialization date: 01-03-2012 02:37 gmt revision:1 [0] [head]

To read:

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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: Fontani-2007.12 tags: mental training skilled motor control date: 01-03-2012 02:33 gmt revision:2 [1] [0] [head]

PMID-18229536[0] Effect of mental imagery on the development of skilled motor actions.

  • with trained subjects (performing something called Ura-Shuto-Uchi (Japanese? but the researchers are Italian)) showed a decrease in reaction time and EMG activity, as well as a increase in movement speed, muscle strength, power, and work. These results did not apply to untrained individuals. EEG also apparently changed vs. the untrained condition.

____References____

[0] Fontani G, Migliorini S, Benocci R, Facchini A, Casini M, Corradeschi F, Effect of mental imagery on the development of skilled motor actions.Percept Mot Skills 105:3 Pt 1, 803-26 (2007 Dec)

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ref: Sergio-1997.08 tags: M1 force tuning kinematics dynamics Kalaska date: 01-03-2012 02:31 gmt revision:1 [0] [head]

PMID-9307146[0] Systematic changes in directional tuning of motor cortex cell activity with hand location in the workspace during generation of static isometric forces in constant spatial directions.

  • The discharge rate of all proximal-arm M1 cells was affected by both hand location and by the direction of static force. w/ interaction between force direction and hand location.
    • this is consistent with cortical units controlling muscle activity directly or through the spinal cord.
  • conclusion: M1 controls muscles directly and contributes to the transformation from extrinsic coordinates to muscle activations while coordinating limb movements.

____References____

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ref: Shulgina-1986.09 tags: reinforcement learning review date: 01-03-2012 02:31 gmt revision:5 [4] [3] [2] [1] [0] [head]

Reinforcement learning in the cortex (a web scour/crawl):

  • http://www.springerlink.com/content/v211201413228x34/
    • short/long interspike intervals via pain reinforcement in immobilized rabbits.
  • PMID-3748636 Increased regularity of activity of cortical neurons in learning due to disinhibitory effect of reinforcement.
    • more rabbit shocking.
  • http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T0F-3S1PT00-P
    • applied glutamate & noradrenaline; both responses are complex.
  • Reinforcement learning in populations of spiking neurons
    • the result: reinforcement learning can function effectively in large populations of neurons if there is a trace of the population activity in addition to the reinforcement signal. this trace must be per-synapes or perhaps per-neuron (as has been anticipated for some time). very important result, helps with the 'specificity' problem.
    • in human terms, the standard reinforcement learning approach is analogous to having a class of students write an exam and being informed by the teacher on the next day whether the majority of students passed or not.
    • this learning method is slow and achieves limited fidelity; in contrast, behavioral reinforcement learning can be reliable and fast. (perhaps this is a result of already-existing maps and or activity in the cortex?)
    • reinforcement learning is almost the opposite of backpropagation, in that in backprop, a error signal is computed per neuron, while in reinforcement learning the error is only computed for the entire system. They posit that there must be a middle ground (need something less than one neuron to compute the training/error signal per neuron, othewise the system would not be very efficient...)
    • points out a good if obvious point: to learn from trial and error different responses to a given stimulus must be explored, and, for this, randomness in the neural activities provides a convenient mechanism.
    • they use the running mean as an eligibility trace per synapse. then change in weight = eta * eligibility trace(t), evaluated at the ends of trials.
    • implemented an asymmetric rule that updates the synapses only slightly if the output is reliable and correct.
    • also needed a population signal or fed-back version of the previous neural behavior. Then individual reinforcement is a product of the reinforcement signal * the population signal * the eligibility trace (the last per synapse). Roughly, if the population signal is different than the eligability trace, and the behavior is wrong, then that synapse should be reinforced. and vice-versa.
  • PMID-17444757 Reinforcement learning through modulation of spike-timing-dependent synaptic plasticity.
    • seems to give about the same result as above, except with STDP: reinforcement-modulated STDP with an eligibility trace stored at each synapse permits learning even if a reward signal is delayed.
    • network can learn XOR problem with firing-rate or temporally coded input.
    • they want someone to look for reward-moduled STDP. paper came out June 2007.
  • PMID: Metaplasticity: the plasticity of synaptic plasticity (1996, Mark Bear)
    • there is such thing as metaplasticity! (plasticity of plasticity, or control over how effective NMDAR are..)
    • he has several other papers on this topic after this..
  • PMID-2682404 Reward or reinforcement: what's the difference? (1989)
    • reward = certain environmental stimuli have the effect of eliciting approach responses. ventral striatum / nucleus accumbens is instrumental for this.
    • reinforcement = the tendency of certain stimuli to strengthen stimulus-response tendencies. dorsolateral striatum is used here.
  • PMID-9463469 Rapid plasticity of human cortical movement representation induced by practice.
  • used TMS to evoke isolated and directionally consistent thumb movements.
  • then asked the volunteers to practice moving their thumbs in an opposite direction
  • after 5-30 minutes of practice, then TMS evoked a response in the practiced direction. wow! this may be short-term memory or the first step in skill learning.
  • PMID-12736341 Learning input correlations through nonlinear temporally asymmetric Hebbian plasticity.
    • temporally asymmetric plasticity is apparently required for a stable network (aka no epilepsy?), and can be optimized to represent the temporal structure of input correlations.

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ref: Cheney-1980.1 tags: M1 kinematics dynamics tuning STA EMG Fetz date: 01-03-2012 02:30 gmt revision:3 [2] [1] [0] [head]

PMID-6253605[0] Functional classes of primate corticomotoneuronal cells and their relation to active force

  • monkeys made ramp and hold torque wrist movements/contractions.
  • corticomotoneuronal cells identified by clear postspike facilitation of rectified EMG activity.
  • all CM cells or PTNs were related to force - with a mixture/diversity of phasic, tonic, and ramp discharge rate profiles.
  • torque trajectory rather than velocity signal seems to be the primnary determinant of cell firing rate...
  • cells appear to be recruited at low force levels..with increasing rates as the torque increases.
  • high firing rates observed > 100!
    • and really low firing rate when there was no torque.

____References____

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ref: Fu-1995.02 tags: M1 motor tuning kinematics dynamic direction date: 01-03-2012 02:21 gmt revision:1 [0] [head]

PMID-7760138[0] Temporal encoding of movement kinematics in the discharge of primate primary motor and premotor neurons

  • 48 target 2D center out task
  • wanted to disambiguate temporal aspects of tuning vs. parallel (e.g. across a neuronal population) aspects of tuning.
  • On average we found a clear temporal segregation and ordering in the onset of the parameter-related partial R2 values: direction-related discharge occurred first (115 ms before movement onset), followed sequentially by target position (57 ms after movement onset) and movement distance (248 ms after movement onset).
  • therefore, the motor cortex seems to have strong temporal processing aspects. duh.
    • Probably explained by Todorov ...

____References____

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ref: Darmanjian-2005.03 tags: recording wifi 802.11 DSP BMI Principe date: 01-03-2012 02:13 gmt revision:2 [1] [0] [head]

IEEE-1419566 (pdf) A Portable Wireless DSP System for a Brain Machine Interface

  • 1400Mw (yuck!!), large design, PCMCIA 802.11 card @ 1.8 Mbps, external SRAM for models
  • implemented LMS and as expected it's faster on the Texas Instruments C33 floating-point DSP.

____References____

Darmanjian, S. and Morrison, S. and Dang, B. and Gugel, K. and Principe, J. Neural Engineering, 2005. Conference Proceedings. 2nd International IEEE EMBS Conference on 112 -115 (2005)

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ref: Mohseni-2004.05 tags: recording amplifier biopotential Mohseni Najafi date: 01-03-2012 01:09 gmt revision:2 [1] [0] [head]

PMID-15132510[0] A fully Integrated Neural Recording Amplifier with DC Input Stabilization

  • The DC stabilization is the interesting part - use subthreshold PMOS transistors.
  • NEF not so good on this one - about 10. {729} much better.

____References____

[0] Mohseni P, Najafi K, A fully integrated neural recording amplifier with DC input stabilization.IEEE Trans Biomed Eng 51:5, 832-7 (2004 May)

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ref: Perelman-2007.01 tags: Technion recording silicon date: 01-03-2012 01:07 gmt revision:2 [1] [0] [head]

PMID-17260864[0] An integrated system for multichannel neuronal recording with spike/LFP separation, integrated A/D conversion and threshold detection.

  • Use an RC filter (5MOhm resistor (polysilicon) + 160pf cap (gate oxide)) to split spike and LFP signals.
  • Weak-inversion MOS transistor to vary the high-pass pole. This can be varied over several orders of magnitude with a DAC (and can be varied to compensate for process variation).
  • Have some good debugging notes on their chip - how the weak inversion MOS transistors leaked more current than expected.

____References____

[0] Perelman Y, Ginosar R, An integrated system for multichannel neuronal recording with spike/LFP separation, integrated A/D conversion and threshold detection.IEEE Trans Biomed Eng 54:1, 130-7 (2007 Jan)

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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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