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{1128} is owned by tlh24.{1126} is owned by tlh24.{852} is owned by tlh24.{433} is owned by tlh24.{578} is owned by tlh24.{548} is owned by tlh24 ryohei.{569} is owned by tlh24 ryohei.{436} is owned by tlh24.{431} is owned by tlh24.
[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] Hochberg LR, Serruya MD, Friehs GM, Mukand JA, Saleh M, Caplan AH, Branner A, Chen D, Penn RD, Donoghue JP, Neuronal ensemble control of prosthetic devices by a human with tetraplegia.Nature 442:7099, 164-71 (2006 Jul 13)

[0] 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] Carpenter MB, Jayaraman A, Subthalamic nucleus of the monkey: connections and immunocytochemical features of afferents.J Hirnforsch 31:5, 653-68 (1990)

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

[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] 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)

[0] Carmena JM, Lebedev MA, Henriquez CS, Nicolelis MA, Stable ensemble performance with single-neuron variability during reaching movements in primates.J Neurosci 25:46, 10712-6 (2005 Nov 16)

[0] Patil PG, Carmena JM, Nicolelis MA, Turner DA, Ensemble recordings of human subcortical neurons as a source of motor control signals for a brain-machine interface.Neurosurgery 55:1, 27-35; discussion 35-8 (2004 Jul)

[0] Nishida M, Walker MP, Daytime naps, motor memory consolidation and regionally specific sleep spindles.PLoS ONE 2:4, e341 (2007 Apr 4)

[0] Rózsa B, Katona G, Kaszás A, Szipöcs R, Vizi ES, Dendritic nicotinic receptors modulate backpropagating action potentials and long-term plasticity of interneurons.Eur J Neurosci 27:2, 364-77 (2008 Jan)

[0] Gage GJ, Ludwig KA, Otto KJ, Ionides EL, Kipke DR, Naive coadaptive cortical control.J Neural Eng 2:2, 52-63 (2005 Jun)

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

[0] Kawato M, Internal models for motor control and trajectory planning.Curr Opin Neurobiol 9:6, 718-27 (1999 Dec)

[0] Scott SH, Optimal feedback control and the neural basis of volitional motor control.Nat Rev Neurosci 5:7, 532-46 (2004 Jul)

[0] Chan SS, Moran DW, Computational model of a primate arm: from hand position to joint angles, joint torques and muscle forces.J Neural Eng 3:4, 327-37 (2006 Dec)

[0] Humphrey DR, Schmidt EM, Thompson WD, Predicting measures of motor performance from multiple cortical spike trains.Science 170:959, 758-62 (1970 Nov 13)

[0] DeLong MR, Strick PL, Relation of basal ganglia, cerebellum, and motor cortex units to ramp and ballistic limb movements.Brain Res 71:2-3, 327-35 (1974 May 17)

[0] Wahnoun R, Helms Tillery S, He J, Neuron selection and visual training for population vector based cortical control.Conf Proc IEEE Eng Med Biol Soc 6no Issue 4607-10 (2004)[1] Wahnoun R, He J, Helms Tillery SI, Selection and parameterization of cortical neurons for neuroprosthetic control.J Neural Eng 3:2, 162-71 (2006 Jun)[2] Fetz EE, Operant conditioning of cortical unit activity.Science 163:870, 955-8 (1969 Feb 28)[3] Fetz EE, Finocchio DV, Operant conditioning of specific patterns of neural and muscular activity.Science 174:7, 431-5 (1971 Oct 22)[4] Fetz EE, Finocchio DV, Operant conditioning of isolated activity in specific muscles and precentral cells.Brain Res 40:1, 19-23 (1972 May 12)[5] Fetz EE, Baker MA, Operantly conditioned patterns on precentral unit activity and correlated responses in adjacent cells and contralateral muscles.J Neurophysiol 36:2, 179-204 (1973 Mar)[6] Humphrey DR, Schmidt EM, Thompson WD, Predicting measures of motor performance from multiple cortical spike trains.Science 170:959, 758-62 (1970 Nov 13)

[0] Sanchez J, Principe J, Carmena J, Lebedev M, Nicolelis MA, Simultaneus prediction of four kinematic variables for a brain-machine interface using a single recurrent neural network.Conf Proc IEEE Eng Med Biol Soc 7no Issue 5321-4 (2004)

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

[0] Cabel DW, Cisek P, Scott SH, Neural activity in primary motor cortex related to mechanical loads applied to the shoulder and elbow during a postural task.J Neurophysiol 86:4, 2102-8 (2001 Oct)

[0] Pollak P, Benabid AL, Gross C, Gao DM, Laurent A, Benazzouz A, Hoffmann D, Gentil M, Perret J, [Effects of the stimulation of the subthalamic nucleus in Parkinson disease]Rev Neurol (Paris) 149:3, 175-6 (1993)

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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: -0 tags: nanophotonics interferometry neural network mach zehnder interferometer optics date: 06-13-2019 21:55 gmt revision:3 [2] [1] [0] [head]

Deep Learning with Coherent Nanophotonic Circuits

  • Used a series of Mach-Zehnder interferometers with thermoelectric phase-shift elements to realize the unitary component of individual layer weight-matrix computation.
    • Weight matrix was decomposed via SVD into UV*, which formed the unitary matrix (4x4, Special unitary 4 group, SU(4)), as well as Σ\Sigma diagonal matrix via amplitude modulators. See figure above / original paper.
    • Note that interfereometric matrix multiplication can (theoretically) be zero energy with an optical system (modulo loss).
      • In practice, you need to run the phase-moduator heaters.
  • Nonlinearity was implemented electronically after the photodetector (e.g. they had only one photonic circuit; to get multiple layers, fed activations repeatedly through it. This was a demonstration!)
  • Fed network FFT'd / banded recordings of consonants through the network to get near-simulated vowel recognition.
    • Claim that noise was from imperfect phase setting in the MZI + lower resolution photodiode read-out.
  • They note that the network can more easily (??) be trained via the finite difference algorithm (e.g. test out an incremental change per weight / parameter) since running the network forward is so (relatively) low-energy and fast.
    • Well, that's not totally true -- you need to update multiple weights at once in a large / deep network to descend any high-dimensional valleys.

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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: -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: -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: 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].


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ref: -2012 tags: parvalbumin interneurons V1 perceptual discrimination mice date: 03-06-2019 01:46 gmt revision:0 [head]

PMID-22878719 Activation of specific interneurons improves V1 feature selectivity and visual perception

  • Lee SH1, Kwan AC, Zhang S, Phoumthipphavong V, Flannery JG, Masmanidis SC, Taniguchi H, Huang ZJ, Zhang F, Boyden ES, Deisseroth K, Dan Y.
  • Optogenetic Activation of PV+ interneurons improves neuronal feature selectivity and improves perceptual discrimination (!!!)

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ref: -2016 tags: MAPseq Zador connectome mRNA plasmic library barcodes Peikon date: 03-06-2019 00:51 gmt revision:1 [0] [head]

PMID-27545715 High-Throughput Mapping of Single-Neuron Projections by Sequencing of Barcoded RNA.

  • Justus M. Kebschull, Pedro Garcia da Silva, Ashlan P. Reid, Ian D. Peikon, Dinu F. Albeanu, Anthony M. Zador
  • Another tool for the toolboxes, but I still can't help but to like microscopy: while the number of labels in MAPseq is far higher, the information per read-oout is much lower; an imaged slice holds a lot of information, including dendritic / axonal morphology, which sequencing doesn't get. Natch, you'd wan to use both, or FISseq + ExM.

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ref: -0 tags: convolutional neural networks audio feature extraction vocals keras tensor flow fourier date: 02-18-2019 21:40 gmt revision:3 [2] [1] [0] [head]

Audio AI: isolating vocals from stereo music using Convolutional Neural Networks

  • Ale Koretzky
  • Fairly standard CNN, but use a binary STFT mask to isolate vocals from instruments.
    • Get Fourier-type time-domain artifacts as a results; but it sounds reasonable.
    • Didn't realize it until this paper / blog post: stacked conv layers combine channels.
    • E.g. Input size 513*25*16 513 * 25 * 16 (512 freq channels + DC, 25 time slices, 16 filter channels) into a 3x3 Conv2D -> 3*3*16+16=1603 * 3 * 16 + 16 = 160 total parameters (filter weights and bias).
    • If this is followed by a second Conv2D layer of the same parameters, the layer acts as a 'normal' fully connected network in the channel dimension.
    • This means there are (3*3*16)*16+16=2320(3 * 3 * 16) * 16 + 16 = 2320 parameters.
      • Each input channel from the previous conv layer has independent weights -- they are not shared -- whereas the spatial weights are shared.
      • Hence, same number of input channels and output channels (in this case; doesn't have to be).
      • This, naturally, falls out of spatial weight sharing, which might be obvious in retrospect; of course it doesn't make sense to share non-spatial weights.
      • See also: https://datascience.stackexchange.com/questions/17064/number-of-parameters-for-convolution-layers
  • Synthesized a large training set via acapella youtube videos plus instrument tabs .. that looked like a lot of work!
    • Need a karaoke database here.
  • Authors wrapped this into a realtime extraction toolkit.

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ref: -2019 tags: Arild Nokland local error signals backprop neural networks mnist cifar VGG date: 02-15-2019 03:15 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

Training neural networks with local error signals

  • Arild Nokland and Lars H Eidnes
  • Idea is to use one+ supplementary neural networks to measure within-batch matching loss between transformed hidden-layer output and one-hot label data to produce layer-local learning signals (gradients) for improving local representation.
  • Hence, no backprop. Error signals are all local, and inter-layer dependencies are not explicitly accounted for (! I think).
  • L simL_{sim} : given a mini-batch of hidden layer activations H=(h 1,...,h n)H = (h_1, ..., h_n) and a one-hot encoded label matrix Y=(y 1,...,y nY = (y_1, ..., y_n ,
    • L sim=||S(NeuralNet(H))S(Y)|| F 2 L_{sim} = || S(NeuralNet(H)) - S(Y)||^2_F (don't know what F is..)
    • NeuralNet()NeuralNet() is a convolutional neural net (trained how?) 3*3, stride 1, reduces output to 2.
    • S()S() is the cosine similarity matrix, or correlation matrix, of a mini-batch.
  • L pred=CrossEntropy(Y,W TH)L_{pred} = CrossEntropy(Y, W^T H) where W is a weight matrix, dim hidden_size * n_classes.
    • Cross-entropy is H(Y,W TH)=Σ i,jY i,jlog((W TH) i,j)+(1Y i,j)log(1(W TH) i,j) H(Y, W^T H) = \Sigma_{i,j} Y_{i,j} log((W^T H)_{i,j}) + (1-Y_{i,j}) log(1-(W^T H)_{i,j})
  • Sim-bio loss: replace NeuralNet()NeuralNet() with average-pooling and standard-deviation op. Plus one-hot target is replaced with a random transformation of the same target vector.
  • Overall loss 99% L simL_sim , 1% L predL_pred
    • Despite the unequal weighting, both seem to improve test prediction on all examples.
  • VGG like network, with dropout and cutout (blacking out square regions of input space), batch size 128.
  • Tested on all the relevant datasets: MNIST, Fashion-MNIST, Kuzushiji-MNIST, CIFAR-10, CIFAR-100, STL-10, SVHN.
  • Pretty decent review of similarity matching measures at the beginning of the paper; not extensive but puts everything in context.
    • See for example non-negative matrix factorization using Hebbian and anti-Hebbian learning in and Chklovskii 2014.
  • Emphasis put on biologically realistic learning, including the use of feedback alignment {1423}
    • Yet: this was entirely supervised learning, as the labels were propagated back to each layer.
    • More likely that biology is setup to maximize available labels (not a new concept).

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ref: -2008 tags: representational similarity analysis fMRI date: 02-15-2019 02:27 gmt revision:1 [0] [head]

PMID-19104670 Representational Similarity Analysis – Connecting the Branches of Systems Neuroscience

  • Nikolaus Kriegeskorte, Marieke Mur, and Peter Bandettini
  • Alright, there seems to be no math in the article (?), but it seems well cited so best be on the radar.
  • RDM = representational dissimilarity matrices
    • Just a symmetric matrix of dissimilarity, e.g. correlation, euclidean distance, absolute activation distance ( L 1L_1 ?)
  • RSA = representational similarity analysis
    • Comparison of the upper triangle of two RDMs, using the same metrics.
    • Or, alternately, second-order isomorphism.
  • So.. high level:

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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: -2019 tags: mosers hippocampus popsci nautilus grid cells date: 02-12-2019 07:32 gmt revision:1 [0] [head]

New Evidence for the Strange Geometry of Thought

  • Wow. Things are organized in 2d structures in the brain. The surprising thing about this article is that only the hiippocampus is mentioned, no discussion of the cortex. Well, it was written by a second year graduate student (though, admittedly, the writing style is perfectly fine.)

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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: 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: 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: -2015 tags: ice charles lieber silicon nanowire probes su-8 microwire extracellular date: 05-30-2018 23:40 gmt revision:3 [2] [1] [0] [head]

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

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

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

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

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

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

PMID-23451719 Synthetic Nanoelectronic Probes for Biological Cells and Tissue

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

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

Materials and technologies for soft implantable neuroprostheses

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

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

Evolutionary Plasticity and Innovations in Complex Metabolic Reaction Networks

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

PMID-22166016 Nanostraws for Direct Fluidic Intracellular Access

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

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

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

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

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

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

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

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

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

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

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

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

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

Thin films and microelectrode arrays for neuroprosthetics

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

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

PMID-8982987 Metallized polymer fibers as leadwires and intrafascicular microelectrodes

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

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

ImageNet Classification with Deep Convolutional Networks

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

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

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

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

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

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

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

Improved polyimide/metal adhesion by chemical modification approaches

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

PLoS One:

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

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

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

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

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

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

PMID-23408972 Credit Assignment during Movement Reinforcement Learning

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

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

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

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

  • unimanual / bimanual tasks.

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

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

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

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

Journal of Neural Engineering:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Nature Methods:

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

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

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

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

Nanowires, useful for Flip's idea.

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

Of personal interest:

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

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

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

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

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

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

  • Debatable causality.

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

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

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

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

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

  • Light and voltage controlled memsistors. Interesting.

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

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

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

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

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

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

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ref: -0 tags: 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.


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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}.


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

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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 .. ???


[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)

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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.

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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}


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

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ref: 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]


[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: Hochberg-2006.07 tags: BMI Donoghue Utah probe Nature tetraplegia Hochberg 2006 date: 01-23-2013 18:49 gmt revision:4 [3] [2] [1] [0] [head]

PMID-16838014[] Neuronal ensemble control of prosthetic devices by a human with tetraplegia

  • patient was able to talk?
  • 96-channel microelectrode array implanted in arm/hand knob or right precentral gyrus.
  • around 30 units / day observed.
  • 90% of units showed significantly varied firing rates (K-S test) during imagined movements.
  • 2D control. Good pursuit tracking and center-out performance.
  • Used Wiener filter.
  • also see the technology review


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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: 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/

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

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

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

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ref: 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


[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: Fuentes-2009.03 tags: Nicoelis DCS spinal cord stimulation PD Fuentes Petersson 6-OHDA date: 03-03-2012 02:46 gmt revision:3 [2] [1] [0] [head]

PMID-19299613[0] Spinal cord stimulation restores locomotion in animal models of Parkinson's disease.

  • Motivation: different levels of cortical oscillation during movement and rest (LFO decreased, medium-high freq increased); PD associated with abnormal synchronous corticostriatal oscillations.
  • In epilepsy patients, stimulation of peripheral nerve afferents is effective in desychronizing low-frequency neural activity, reducing the frequency and duration of seizures (8,9,10) PMID-11050139[1] PMID-16886985[2] PMID-18188148[3]
  • DCS (dorsal column stimulation)
    • Epidural, longitudal electrodes, horizontal electrical field.
    • Upper thoracic, mice.
    • 300Hz.
    • simpler and safer than brain surgery.
    • [24] DCS induces no increase in arousal. (Wall, PD. Brain 1970; 93:505.
  • used the tyrosine hydroxyalse inhibitor AMPT
  • M1 LFP: Osc around 1.5-4Hz and 10-15Hz enhanced; osc > 25Hz subdued.
  • DCS increased locomotion by 29x in depleted animals, and 4.9x in normal animals.
  • Also titrated L-DOPA with DAT-KO mice. Without dopamine, there is no movement.
    • DCS increased L-DOPA effectiveness by 5x (1/5 the dose was required)
  • Verified in a 6-OHDA lesion model in rats.
    • Lesioned animals moved more, sham moved less.
  • Activation of locomotion is via striatal medium spiny neurons projecting to the output nuclei of the basal ganglia [26 PMID-8402406[4] ,27 PMID-1695404[5]].
  • In PD, with reduced striatal dopamine levels, the activation threshold of the projection neurons from the striatum is significantly increased [25] PMID-17916382[6].


[0] Fuentes R, Petersson P, Siesser WB, Caron MG, Nicolelis MA, Spinal cord stimulation restores locomotion in animal models of Parkinson's disease.Science 323:5921, 1578-82 (2009 Mar 20)
[1] Fanselow EE, Reid AP, Nicolelis MA, Reduction of pentylenetetrazole-induced seizure activity in awake rats by seizure-triggered trigeminal nerve stimulation.J Neurosci 20:21, 8160-8 (2000 Nov 1)
[2] DeGiorgio CM, Shewmon A, Murray D, Whitehurst T, Pilot study of trigeminal nerve stimulation (TNS) for epilepsy: a proof-of-concept trial.Epilepsia 47:7, 1213-5 (2006 Jul)
[3] George MS, Nahas Z, Bohning DE, Lomarev M, Denslow S, Osenbach R, Ballenger JC, Vagus nerve stimulation: a new form of therapeutic brain stimulation.CNS Spectr 5:11, 43-52 (2000 Nov)
[4] Brudzynski SM, Wu M, Mogenson GJ, Decreases in rat locomotor activity as a result of changes in synaptic transmission to neurons within the mesencephalic locomotor region.Can J Physiol Pharmacol 71:5-6, 394-406 (1993 May-Jun)
[5] DeLong MR, Primate models of movement disorders of basal ganglia origin.Trends Neurosci 13:7, 281-5 (1990 Jul)
[6] Grillner S, Wallén P, Saitoh K, Kozlov A, Robertson B, Neural bases of goal-directed locomotion in vertebrates--an overview.Brain Res Rev 57:1, 2-12 (2008 Jan)

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ref: Plaha-2008.05 tags: zona incerta DBS date: 03-03-2012 01:45 gmt revision:4 [3] [2] [1] [0] [head]

PMID-18037630[0] Bilateral stimulation in the caudal zona incerta nucleus for tremor control

  • VL DBS does not always work, and patients may develop tolerance; tried instead the caudal Zona Incerta (cZI).
    • VL ~= VIM (?) -- differing thalamic naming nomenclatures -- see {1100}.
    • VL does not always work for proximal tremor.
  • nice results! Resting PD tremor improved by 94.8% and postural tremor by 88.2%. The total tremor score improved by 75.9% in 6 patients with ET
    • Works for both distal and proximal tremor.
  • Original finding: PMID-18671648
  • nice figure therein.


[0] Plaha P, Khan S, Gill SS, Bilateral stimulation of the caudal zona incerta nucleus for tremor control.J Neurol Neurosurg Psychiatry 79:5, 504-13 (2008 May)

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ref: Pollak-2002.01 tags: Benabid DBS VIM date: 03-02-2012 22:20 gmt revision:12 [11] [10] [9] [8] [7] [6] [head]

Relevant papers:

  • 1 PMID-11948771[0] Intraoperative micro- and macrostimulation of the subthalamic nucleus in Parkinson's disease.
    • Suggest using microelectrodes for precise mapping of suitable target area.
  • 2 PMID-11948758[1] Mechanisms of deep brain stimulation.
    • The mechanism could be either one or a combination of several causes: jamming of a feedback loop, activation of inhibitory structures included in a more complex network, blockade of membrane ion channels, deplorisation blockade, synaptic exhaustion, induction of early genes, changes in local blood flow, neuroplasticity. (I think that it's likely some sort of information block, since it's so immediately efficacious).
    • Emphasis on neuroplasticity.
  • 3 PMID-9400514[2] Stimulation of subthalamic nucleus alleviates tremor in Parkinson's disease.
    • Stimulation of the ventral intermediate nucleus of the thalamus (Vim) greatly improves tremor in 88% of patients with PD, but rigidity is only moderately improved and akinesia is not improved.
    • In patients with tremor-dominated PD, STN stimulation should be preferred to Vim stimulation since most of these patients will develop disabling akinesia not improved by Vim stimulation.
  • 4 PMID-7631092[3] Acute and long-term effects of subthalamic nucleus stimulation in Parkinson's disease.
    • The final position of the chronic electrodes was optimized using electrophysiological recording and stimulation along with clinical assessment and surface EMG of agonist and antagonist muscles of the examined limbs.
    • things have not changed much since then - 130 Hz, quadripolar medtronic electrode, electrophysiological and stereotaxic guidance.
    • no dyskinesia or hemiballismus observed.
  • 5 PMID-8235208[4] [Effects of the stimulation of the subthalamic nucleus in Parkinson disease].
    • same as above, but in French, and first.
  • 6 PMID-19081516[5] Deep brain stimulation of the subthalamic nucleus for the treatment of Parkinson's disease.
    • Side effects are mainly neurocognitive, with side-effects created by spread of stimulation to surrounding structures, depending on the precise location of electrodes.
    • Little pressure to optimize in the present system.
    • Needs to be extended to developing countries, too.
  • 7 PMID-17960811[6] Lifetime of Itrel II pulse generators for subthalamic nucleus stimulation in Parkinson's disease.
    • They last 83 +- 14 months -- wow!
    • Replace the device when the battery gets low. duh.
  • 8 PMID-15975946[7] Bilateral deep brain stimulation in Parkinson's disease: a multicentre study with 4 years follow-up.
    • DBS to the STN is effective.
      • assessed 3-4 years relative to baseline, UPDRS-III score.
      • Good mobility wityhout dyskinesias, better activities of daily living.
    • side effects: cognitive decline, speech difficulty, instability, gait disorders and depression.
  • 9 PMID-15040711[8] Deep brain stimulation of the subthalamic nucleus in Parkinson's disease 1993-2003: where are we 10 years on?
    • Efficacy still somewhat not clear.
    • STN improves motor function by at least 60% (!), and reduces the levodopa requirement.
    • Reviews some pathophysiology & basic science.


  • 10 PMID-15197715[9] Partial lesion of thalamic ventral intermediate nucleus after chronic high-frequency stimulation.
    • 60% cell loss within 0.5mm of the electrode tip.
    • still, tremor improvement attributable to chronic stimulation, not microthalamotomy.
  • 11 PMID-8592222[10] Chronic electrical stimulation of the ventralis intermedius nucleus of the thalamus as a treatment of movement disorders.
    • Ventralis intermedius stimulation has since been used by the authors over the last 8 years as a treatment in 117 patients with movement disorders (80 cases of Parkinson's disease, 20 cases of essential tremor, and 17 cases of various dyskinesias and dystonias including four multiple sclerosis)
    • Chronic VIM stimulation, which is reversible, adaptable, and well tolerated even by patients undergoing bilateral surgery (74 of 117 patients) and by elderly patients, should replace thalamotomy in the regular surgical treatment of parkinsonian and essential tremors.
  • 12 PMID-8748831[11] Stimulation of the ventral intermediate thalamic nucleus in tremor dominated Parkinson's disease and essential tremor.
    • LFS of VIM increases tremor, whereas HFS decreases it.
  • 13 PMID-8453462[12] Thalamic stimulation and suppression of parkinsonian tremor. Evidence of a cerebellar deactivation using positron emission tomography.
    • The suppression of tremor was specifically associated with a decrease of rCBF (PET) in the cerebellum, whereas the ineffective stimulation induced a decrease of rCBF in ipsilateral cerebral cortex.
  • 14 PMID-8420163[13] Long-term effects of chronic stimulation of the ventral intermediate thalamic nucleus in different types of tremor.
    • folow up.
    • HFS to the VIM in 26 PD, 6 ET patients.
    • Of the 43 thalami stimulated, 27 showed complete relief from tremor and 11 major improvement (88%).
    • Much better than thalamotomy.
  • 15 PMID-1671433[14] Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus.
    • same as above, but with abstract. 1991 -- original.

Stem cells / Gene therapy:

  • 16 PMID-16902198[15] Functional neuronal differentiation of bone marrow-derived mesenchymal stem cells.
    • cells express markers for neurons (shape, NF-L beta-tubulin.
    • cells can differentiate along the neural pathway.
    • but how will they migrate properly? hum, need a review on this.
  • 17 PMID-21087733[16] Gene therapy for Parkinson's disease: do we have the cure?
    • Levodopa dyskinesias occur 5-10 years after treatment start and decrease the benefit of treatment.
    • Levodopa does not alter the course of PD.
    • Neural grafts for PD have been in development for three decades now, yet they are still considered experimental as they have not provided therapeutic benefit.
    • Marks and colleagues report results of the first double-blind phase 2 trial for gene therapy of PD.
      • This involves growth factors, retrogradely transported from the striatum to the SNpc.
      • only saw effect at 18 months -- may have taken a long time for the gene to be expressed?
    • Gene therapy can cure. DBS cannot.
    • need to test with dopa-radiography PET scans.
    • might cause cancer.
    • See [17][18][19][20][21]


  • PMID-12725785[22] An unsupervised automatic method for sorting neuronal spike waveforms in awake and freely moving animals.
  • PMID-19882716[23] Neuroprotection of midbrain dopaminergic cells in MPTP-treated mice after near-infrared light treatment.


[0] Pollak P, Krack P, Fraix V, Mendes A, Moro E, Chabardes S, Benabid AL, Intraoperative micro- and macrostimulation of the subthalamic nucleus in Parkinson's disease.Mov Disord 17 Suppl 3no Issue S155-61 (2002)
[1] Benabid AL, Benazzous A, Pollak P, Mechanisms of deep brain stimulation.Mov Disord 17 Suppl 3no Issue S73-4 (2002)
[2] Krack P, Pollak P, Limousin P, Benazzouz A, Benabid AL, Stimulation of subthalamic nucleus alleviates tremor in Parkinson's disease.Lancet 350:9092, 1675 (1997 Dec 6)
[3] Benabid AL, Pollak P, Gross C, Hoffmann D, Benazzouz A, Gao DM, Laurent A, Gentil M, Perret J, Acute and long-term effects of subthalamic nucleus stimulation in Parkinson's disease.Stereotact Funct Neurosurg 62:1-4, 76-84 (1994)
[4] Pollak P, Benabid AL, Gross C, Gao DM, Laurent A, Benazzouz A, Hoffmann D, Gentil M, Perret J, [Effects of the stimulation of the subthalamic nucleus in Parkinson disease].Rev Neurol (Paris) 149:3, 175-6 (1993)
[5] Benabid AL, Chabardes S, Mitrofanis J, Pollak P, Deep brain stimulation of the subthalamic nucleus for the treatment of Parkinson's disease.Lancet Neurol 8:1, 67-81 (2009 Jan)
[6] Anheim M, Fraix V, Chabardès S, Krack P, Benabid AL, Pollak P, Lifetime of Itrel II pulse generators for subthalamic nucleus stimulation in Parkinson's disease.Mov Disord 22:16, 2436-9 (2007 Dec)
[7] Rodriguez-Oroz MC, Obeso JA, Lang AE, Houeto JL, Pollak P, Rehncrona S, Kulisevsky J, Albanese A, Volkmann J, Hariz MI, Quinn NP, Speelman JD, Guridi J, Zamarbide I, Gironell A, Molet J, Pascual-Sedano B, Pidoux B, Bonnet AM, Agid Y, Xie J, Benabid AL, Lozano AM, Saint-Cyr J, Romito L, Contarino MF, Scerrati M, Fraix V, Van Blercom N, Bilateral deep brain stimulation in Parkinson's disease: a multicentre study with 4 years follow-up.Brain 128:Pt 10, 2240-9 (2005 Oct)
[8] Ashkan K, Wallace B, Bell BA, Benabid AL, Deep brain stimulation of the subthalamic nucleus in Parkinson's disease 1993-2003: where are we 10 years on?Br J Neurosurg 18:1, 19-34 (2004 Feb)
[9] Henderson J, Rodriguez M, O'Sullivan D, Pell M, Fung V, Benabid AL, Halliday G, Partial lesion of thalamic ventral intermediate nucleus after chronic high-frequency stimulation.Mov Disord 19:6, 709-11 (2004 Jun)
[10] Benabid AL, Pollak P, Gao D, Hoffmann D, Limousin P, Gay E, Payen I, Benazzouz A, Chronic electrical stimulation of the ventralis intermedius nucleus of the thalamus as a treatment of movement disorders.J Neurosurg 84:2, 203-14 (1996 Feb)
[11] Alesch F, Pinter MM, Helscher RJ, Fertl L, Benabid AL, Koos WT, Stimulation of the ventral intermediate thalamic nucleus in tremor dominated Parkinson's disease and essential tremor.Acta Neurochir (Wien) 136:1-2, 75-81 (1995)
[12] Deiber MP, Pollak P, Passingham R, Landais P, Gervason C, Cinotti L, Friston K, Frackowiak R, Mauguière F, Benabid AL, Thalamic stimulation and suppression of parkinsonian tremor. Evidence of a cerebellar deactivation using positron emission tomography.Brain 116 ( Pt 1)no Issue 267-79 (1993 Feb)
[13] Pollak P, Benabid AL, Gervason CL, Hoffmann D, Seigneuret E, Perret J, Long-term effects of chronic stimulation of the ventral intermediate thalamic nucleus in different types of tremor.Adv Neurol 60no Issue 408-13 (1993)
[14] Benabid AL, Pollak P, Gervason C, Hoffmann D, Gao DM, Hommel M, Perret JE, de Rougemont J, Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus.Lancet 337:8738, 403-6 (1991 Feb 16)
[15] Tropel P, Platet N, Platel JC, Noël D, Albrieux M, Benabid AL, Berger F, Functional neuronal differentiation of bone marrow-derived mesenchymal stem cells.Stem Cells 24:12, 2868-76 (2006 Dec)
[16] Benabid AL, Gene therapy for Parkinson's disease: do we have the cure?Lancet Neurol 9:12, 1142-3 (2010 Dec)
[17] Marks WJ Jr, Bartus RT, Siffert J, Davis CS, Lozano A, Boulis N, Vitek J, Stacy M, Turner D, Verhagen L, Bakay R, Watts R, Guthrie B, Jankovic J, Simpson R, Tagliati M, Alterman R, Stern M, Baltuch G, Starr PA, Larson PS, Ostrem JL, Nutt J, Kieburtz K, Kordower JH, Olanow CW, Gene delivery of AAV2-neurturin for Parkinson's disease: a double-blind, randomised, controlled trial.Lancet Neurol 9:12, 1164-72 (2010 Dec)
[18] Herzog CD, Dass B, Holden JE, Stansell J 3rd, Gasmi M, Tuszynski MH, Bartus RT, Kordower JH, Striatal delivery of CERE-120, an AAV2 vector encoding human neurturin, enhances activity of the dopaminergic nigrostriatal system in aged monkeys.Mov Disord 22:8, 1124-32 (2007 Jun 15)
[19] Kordower JH, Herzog CD, Dass B, Bakay RA, Stansell J 3rd, Gasmi M, Bartus RT, Delivery of neurturin by AAV2 (CERE-120)-mediated gene transfer provides structural and functional neuroprotection and neurorestoration in MPTP-treated monkeys.Ann Neurol 60:6, 706-15 (2006 Dec)
[20] Kordower JH, Emborg ME, Bloch J, Ma SY, Chu Y, Leventhal L, McBride J, Chen EY, Palfi S, Roitberg BZ, Brown WD, Holden JE, Pyzalski R, Taylor MD, Carvey P, Ling Z, Trono D, Hantraye P, Déglon N, Aebischer P, Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson's disease.Science 290:5492, 767-73 (2000 Oct 27)
[21] Eslamboli A, Georgievska B, Ridley RM, Baker HF, Muzyczka N, Burger C, Mandel RJ, Annett L, Kirik D, Continuous low-level glial cell line-derived neurotrophic factor delivery using recombinant adeno-associated viral vectors provides neuroprotection and induces behavioral recovery in a primate model of Parkinson's disease.J Neurosci 25:4, 769-77 (2005 Jan 26)
[22] Aksenova TI, Chibirova OK, Dryga OA, Tetko IV, Benabid AL, Villa AE, An unsupervised automatic method for sorting neuronal spike waveforms in awake and freely moving animals.Methods 30:2, 178-87 (2003 Jun)
[23] Shaw VE, Spana S, Ashkan K, Benabid AL, Stone J, Baker GE, Mitrofanis J, Neuroprotection of midbrain dopaminergic cells in MPTP-treated mice after near-infrared light treatment.J Comp Neurol 518:1, 25-40 (2010 Jan 1)

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ref: -0 tags: locomotion decerebrated monkeys spinal cord section STN stimulation date: 03-01-2012 23:53 gmt revision:0 [head]

PMID-7326562 Locomotor control in macaque monkeys

  • Were not able to induce walking with in monkeys with a sectioned spinal cord
  • Were able to induce walking motion by pulsed stimulation of the STN, with varying walking speed with varying currents!
  • Detailed, informative report, more than I have time to record here today.

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ref: -0 tags: DBS dopamine synaptic plasticity striatum date: 02-27-2012 21:57 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

PMID-11285003 Dopaminergic control of synaptic plasticity in the dorsal striatum.

  • Repetitive stimulation of corticostriatal fibers causes a massive release of glutamate and DA in the striatum, and depending on the glutamate receptor subtype preferentially activated, produces either long-term depression (LTD) or long-term potentiation (LTP) of excitatory synaptic transmission.
  • D1 and D2 (like) receptors interact synergistically to allow LTD formation, and in opposition while inducing LTP.
  • Stimulation of DA receptors has been shown to modulate voltage-dependent conductances in striatal spiny neurons, but it does not cause depolarization or hyperpolarization (Calabresi et al 2000a PMID-11052221; Nicola et al 2000)
  • Striatal spiny neurons present a high degree of colocalization of subtypes of DA and glutamate receptors. PMID-9215599
  • Striatal cells have up and down states. Wilson and Kawaguchi 1996 PMID-8601819
  • Both LTD and LTP are induced in the striatum by the repetitive stimulation of corticostriatal fibers.
    • Repetition is associated with the dramatic increase of both glutamate and DA in the striatum. (presynaptic?)
  • LTP is enhanced by blocking or removing D2 receptors.
  • More complexity here - in terms of receptors and blocking. (sure magnesium blocks NMDA receptors, but there are many other drugs used...)

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ref: -0 tags: 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: 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.


[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: Holgado-2010.09 tags: DBS oscillations beta globus pallidus simulation computational model date: 02-22-2012 18:36 gmt revision:4 [3] [2] [1] [0] [head]

PMID-20844130[0] Conditions for the Generation of Beta Oscillations in the Subthalamic Nucleus–Globus Pallidus Network

  • Modeled the globus pallidus external & STN; arrived at criteria in which the system shows beta-band oscillations.
    • STN is primarily glutamergic and projects to GPe (along with many other areas..)
      • STN gets lots of cortical afferent, too.
    • GPe is GABAergic and projects profusely back to STN.
    • This inhibition leads to more accurate choices.
      • (Frank, 2006 PMID:,
        • The present [neural network] model incorporates the STN and shows that by modulating when a response is executed, the STN reduces premature responding and therefore has substantial effects on which response is ultimately selected, particularly when there are multiple competing responses.
        • Increased cortical response conflict leads to dynamic adjustments in response thresholds via cortico-subthalamic-pallidal pathways.
        • the model accounts for the beneficial effects of STN lesions on these oscillations, but suggests that this benefit may come at the expense of impaired decision making.
        • Not totally convinced -- impulsivity is due to larger network effects. Delay in conflict situations is an emergent property, not localized to STN.
      • Frank 2007 {1077}.
  • Beta band: cite Boraud et al 2005.
  • Huh parameters drawn from Misha's work, among others + Kita 2004, 2005.
    • Striatum has a low spike rate but high modulation? Schultz and Romo 1988.
  • In their model there are a wide range of parameters (bidirectional weights) which lead to oscillation
  • In PD the siatum is hyperactive in the indirect path (Obeso et al 2000); their model duplicates this.


[0] Holgado AJ, Terry JR, Bogacz R, Conditions for the generation of beta oscillations in the subthalamic nucleus-globus pallidus network.J Neurosci 30:37, 12340-52 (2010 Sep 15)

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ref: Prescott-2009.02 tags: PD levodopa synaptic plasticity SNr STN DBS date: 02-22-2012 18:28 gmt revision:2 [1] [0] [head]

PMID-19050033[0] Levodopa enhances synaptic plasticity in the substantia nigra pars reticulata of Parkinson's disease patients

  • In the SNpc -> SNr.
  • High frequency stimulation (HFS--four trains of 2 s at 100 Hz) in the SNr failed to induce a lasting change in test fEPs (1 Hz) amplitudes in patients OFF medication (decayed to baseline by 160 s). Following oral L-dopa administration, HFS induced a potentiation of the fEP amplitudes (+29.3% of baseline at 160 s following a plateau).
  • Aberrant synaptic plasticity may play a role in the pathophysiology of Parkinson's disease.


[0] Prescott IA, Dostrovsky JO, Moro E, Hodaie M, Lozano AM, Hutchison WD, Levodopa enhances synaptic plasticity in the substantia nigra pars reticulata of Parkinson's disease patients.Brain 132:Pt 2, 309-18 (2009 Feb)

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ref: RodriguezOroz-2011.01 tags: DBS dopamine impulse control spain pamplona ventral beta date: 02-22-2012 17:02 gmt revision:9 [8] [7] [6] [5] [4] [3] [head]

PMID-21059746[0] Involvement of the subthalamic nucleus in impulse control disorders associated with Parkinson’s disease

  • recorded LFP in the STN of 28 patients.
    • of these 10 had impulse control disorders, 9 had dyskinesias, and 9 had no complications.
  • compared ON and OFF medication.
  • no difference between groups in off states.
  • large differences in ON states.
    • Impulse control problems: theta-alpha activity(4-10 Hz) 6 Hz mean.
      • Larger coherence with frontal regions 4-7.5 Hz.
    • Dyskinesias: higher frequency theta-alpha 8 Hz mean.
      • Higher coherence with motor areas, 7.5 - 10Hz.
    • No problems: no noticeable LFP oscillations (?).
  • PD patients often have side-effects of Punding and hobbyism.
    • Does meth treat PD? Selegiline does. Fascinating history there regarding combining MAOI + amphetamine --> effective PD drug.
    • Why does both meth and levodopa induce impulsivity?
    • Some of the other effects of L-DOPA treatment: hypersexuality, manic behavior or shopping.
    • Lesion of the subthalamic nucleus by infarction or tumor is associated with behavioral alterations including agitation, manic states and logorrhoea, with or without hemiballismus.
  • In some patients with ICD (impulse control disorders) induced by subthalamic nucleus deep brain stimulation, the abnormal behavior was provoked by stimulation with a ventral contact and suppressed by switching it off. (dorsal region is more motor).
    • In three patients with ICD, stimulation through the ventral contact induced a euphoric state -- PPN?
  • STN recordings from rats and monkeys modify their frequency in response to reward related tasks (Aron and Poldrack 2006); in humans the STN is active during an inhibition task (LI et al 2008).
  • LFP recordings from the treatment electrode were very low! 16uV.
  • Typical results show large differences between ON and OFF: ON show more activity > 60 Hz, OFF more < 60 Hz (Brown et al 2001; Brown 2003 Gatev et al 2006).
  • LFP recordings in PD patients from the STN showed that emotional stimulus led to a decrease in alpha power in the ventral contacts (Brucke et al 2007), whereas active movement led to a decrease in the beta power recorded in the dorsal subthalamic nucleus (Alegre et al 2005).
  • Original work on STN mediating impulsivity: Delong 1983 PMID-6422317 The neurophysiologic basis of abnormal movements in basal ganglia disorders.
    • Single cell studies in the basal ganglia of behaving animals have revealed specific relations of neuronal activity to movements of individual body parts and a relation to specific parameters of movement, particularly direction, amplitude, and velocity. (no fulltext available).


[0] Rodriguez-Oroz MC, López-Azcárate J, Garcia-Garcia D, Alegre M, Toledo J, Valencia M, Guridi J, Artieda J, Obeso JA, Involvement of the subthalamic nucleus in impulse control disorders associated with Parkinson's disease.Brain 134:Pt 1, 36-49 (2011 Jan)

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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.


[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?


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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.


[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: 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.


[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: Gubellini-2009.09 tags: DBS PD 2009 review historical microstimulation ICMS chronaxie rheobase date: 02-22-2012 14:33 gmt revision:11 [10] [9] [8] [7] [6] [5] [head]

PMID-19559747[0] Deep brain stimulation in neurological diseases and experimental models: from molecule to complex behavior.

  • Wow, DBS has been used since the 1950s for localization of lesion targets; in the 1960's was discovered to alleviate tremor; 70s and 80s targeted at the cerebellum for treatimng movement disorders or epilepsy.
  • Extensive list of all the other studies & their stimulation protocols.
  • Large mylenated fibers have chronaxies ranging aruond 30-200 us, while cell bodies and dendrites this value is around 1-10ms. (Rank, 1975).
    • Lapique: minimum energy is a/b, where b is the rhreobase (the minimal electric current of infinite duration that results in an action potential), and chronaxie is the minimum time over which an electric current double the strength of the rheobase needs to be applied in order ti stimulate a nerve cell.
    • Q(t)t=U rh(1+t cht) \frac{Q(t)}{t} = U_{rh}(1 + \frac{t_ch}{t}) where U rhU_{rh} is the rheobase and t cht_{ch} is the chronaxie.
    • you can simplify this to: I th=I rh(1+t cht) I_{th} = I_{rh} (1 + \frac{t_{ch}}{t}) where I rhI_{rh} is the rheobase current and I thI_{th} is the threshold current (Irnich, 2002).
  • Measurements of chronaxie in VIM and GPi found values of 60-75us, hence DBS effects are likely mediated through the activation of afferent and efferent axons. (Holsheimer et al 2000a, 2000b)
    • In line with these findings, cortical stimulation also results in the activation of afferent and efferent axons (Nowak and Bullier, 1998a, 1998b PMID-9504844).
    • Ustim can result in cell body hyperpolarization coupled with action potential initiation in the axon (McIntyre and Grill, 1999; Nowak and Bullier 1998a b).
  • Stimulation depends on the direction of the electric field, obviously. When the axons and E\vec{E} are ||.
  • Acute stimulation is different from chronic DBS (as used in patients); it may be a mistake to extrapolate conclusions.
    • DBS electrodes become encapsulated, and current delivered hence decreases.
  • Strong placebo effect of just the DBS surgery.
    • Implantation of electrodes alone had therapeutic benefit in 6-mo trial. (Mann et al 2009).
  • mean lead impedance is 400-120 ohms in clinical DBS leads, PT-IR.
    • platinum is relatively non-toxic to the brain when compared to metals such as gold or rhodium.
  • If stimulation exceeds 30 uC/cm^2/phase, there is a risk of tissue damage. This equates to 30ma.
  • Stainless steel electrodes are damadged by days of in vivo stimulation -- metal ions are lost.
  • STN neurons spontaneously oscillate due to leak Ca currents and C-activated K channels.
  • STN DBS seems to disrupt abnormal synchronized activity recorded in the BG-thalamocortical loops in PD. (meta-analysis of several studies).
  • STN DBS seems to reduce FR in the SNr.
  • STN excitotoxic leasion in rats causes increased impulsivity, impaired accuracy, premature responses, and more attention to food reward location in rats.
    • There is a hyperdirect pathway from the medial prefrontal cortex to the STN; breaking this decreases attention and perseverance.
    • STN HFS sometimes induces impulsive behavior in humans, with which this is consistent. (This may be sequelae from levodopa treatment).
    • STN HFS often causes weight gain in patients. But it might be because they can eat more or are more 'motivated at life'.
    • Controlled studies in rats show that STN lesion does not effect quantity consumed, either food, ehanol, or cocaine.
      • Differential effect when the reward was food vs. cocaine -- the STN may modulate the reward system based on the nature of the reward.
  • Huh: HFS of the ZI (zona incerta) has been reported to be superior to STN HFS for improving contralateral parkinsonism in PD patients.
    • Could be current diffusion into the STN, however, as lesioning this structure in rats has less effect than lesioning STN.
    • See also {1098}.
  • Chronic GPi DBS does not allow reducing L-DOPA dosage, unlike STN stimulation, but it is a good treatment for dyskinesia.
  • VIM treatment is very effective for tremor, but it does not treat the other motor symptoms of PD. Furthermore, it wears off after a few years.
    • CM/Pf seems like an even better target (Center median / parafasicular complex of the thalamus -- see {1119}.
  • DBS in the PPN (pedunculo pontine nucleus, brainstem target of the BG) at 10 HZ induces a feeling of well-being , concomitant with a modest improvement in motor function; no effect at 80 Hz.
  • Dystonia: GPi is a efficacious target for DBS.
    • Full effect takes a year (!), suggesting that the effect is through reorganization of the BG / neuroplascticity.
  • ET : lesions of the VIM, STN, or cerebellum can reduce symptoms. DBS of the VIM, STN, or ZI all have been found effective.
  • Huntington's disease involves degeneration of the projection neurons from the caudate and putamen.
    • HD affects motor, cognitive, and psychiatric functioning.
  • Drug addiction: inactivating the Nucelus accumbens (NAc) may reduce motivation to obtain the drug, but it may also reduce the motivation to do anything (apathy).
  • GPi DBS also a target for reducing chorea.
  • STN DBS may worsen treatment-resistant-depression; this seen in an animal model, and anecdotally in humans with PD.
  • OCD can be treated with DBS through the internal capsule extending toward the NAc / ventral striatum.
    • side effects include hypomania or anxiety.
    • Alas there is no satisfactory animal model of OCD, which hampers research.


[0] Gubellini P, Salin P, Kerkerian-Le Goff L, Baunez C, Deep brain stimulation in neurological diseases and experimental models: from molecule to complex behavior.Prog Neurobiol 89:1, 79-123 (2009 Sep)

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ref: Benabid-2011.01 tags: DBS BMI Benabid date: 02-16-2012 17:48 gmt revision:3 [2] [1] [0] [head]

PMID-21867795[0] Deep brain stimulation: BCI at large, where are we going to?

  • Everybody on the bandwagon! Talks about their efforts to make a BCI using DBS techniques / electrodes.
  • Language is a bit telegraphic, perhaps because it's translated from the French.
  • Tested in rats using an 1D ECoG BMI.
  • Posits that DBS is just a particularly simple form of BMI.


[0] Benabid AL, Costecalde T, Torres N, Moro C, Aksenova T, Eliseyev A, Charvet G, Sauter F, Ratel D, Mestais C, Pollak P, Chabardes S, Deep brain stimulation: BCI at large, where are we going to?Prog Brain Res 194no Issue 71-82 (2011)

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ref: Sato-2000.08 tags: STN anatomy DBS date: 02-15-2012 03:43 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-10888744[0] Axonal branching pattern of neurons of the subthalamic nucleus in primates

  • 5 disctinct STN projection neurons:
    • projecting to the SNr, GPi and GPe (21.3%)
    • SNr and GPe (2.7%)
    • GPI and GPe (48%)
    • GPe only (10.7%)
    • Axons toward the striatum, but whose terminal arborization could not be visualized (17.3%)
  • collaterals are highly patterned and have specific subtypes
  • ramify on the two output structures, the GPi and SNr.
  • more camera-lucida beautiful computerized drawings/tracings.


[0] Sato F, Parent M, Levesque M, Parent A, Axonal branching pattern of neurons of the subthalamic nucleus in primates.J Comp Neurol 424:1, 142-52 (2000 Aug 14)

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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


[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: Carpenter-1990.01 tags: STN afferents anatomy DBS date: 01-26-2012 17:19 gmt revision:4 [3] [2] [1] [0] [head]

PMID-1707079 Subthalamic nucleus of the monkey: connections and immunocytochemical features of afferents.

  • retrograde and anterograde transport of horseradish peroxidase injected into parts of the STN.
  • did not label any afferents from the frontal cortex or CM/Pf, possibly because they are collaterals of projections to other areas.
  • is the globus pallidus arranged in rostral-caudal dorso-ventral parallel layers? the afferents seem to be so.


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

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

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


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

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ref: Klawans-1976.12 tags: STN DBS heminallisms date: 01-26-2012 17:17 gmt revision:3 [2] [1] [0] [head]

PMID-980081[0] Treatment and prognosis of hemiballismus.

  • Acute hemiballismus due to a cerebrovascular lesion may have a grave prognosis. In the past nine years, we have treated 11 patients who had an acute onset of hemiballismus believed to be the result of an acute vascular lesion with neuroleptic drugs (most frequently haloperidol). None of the 11 died, and the movement disorders were greatly reduced or eliminated. In eight patients the drugs were withdrawn within six months, without recurrence of the movement disorders. Spinal-fluid homovanillic acid levels were increased in three patients, suggesting that altered dopaminergic feedback mechanisms may be involved in the pathophysiology of hemiballismus. Our observations suggest that the prognosis of hemiballismus is not necessarily as grave as has been believed, and that neuroleptic therapy may alter the outcome of this disorder.


[0] Klawans HL, Moses H 3rd, Nausieda PA, Bergen D, Weiner WJ, Treatment and prognosis of hemiballismus.N Engl J Med 295:24, 1348-50 (1976 Dec 9)

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ref: Benabid-2005.12 tags: Benabid famous DBS STN review date: 01-25-2012 00:22 gmt revision:2 [1] [0] [head]

PMID-16280671[0] Deep-brain stimulation in Parkinson's disease: long-term efficacy and safety - What happened this year?

  • 260 reports on DBS in 2004!
  • (from the abstract) There is an urgent need for the organization of research and reports, and no need to report small series replicating well-established conclusions. oopsie.
  • Clinical reports should concentrate on unobserved effects in relation to causative parameters, based on the precise location of electrodes,
  • and on clinical reports comparable between teams and on methods to optimize and facilitate the tuning of parameters and postoperative evaluations in order to make this treatment easier to provide for the neurologist


[0] Benabid AL, Chabardès S, Seigneuret E, Deep-brain stimulation in Parkinson's disease: long-term efficacy and safety - What happened this year?Curr Opin Neurol 18:6, 623-30 (2005 Dec)

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ref: -0 tags: feedback stability resonance butterworth matlab date: 01-22-2012 03:46 gmt revision:4 [3] [2] [1] [0] [head]

Just fer kicks, I tested what happens to low-order butterworth filters when you maladjust one of the feedback coefficients.

[B, A] = butter(2, 0.1);
[h, w] = freqz(B,A);
A(2) = A(2) * 0.9;
[h2, ~] = freqz(B,A);
hold off
hold on; plot(w,abs(h2), 'r')
title('10% change in one FB filter coef 2nd order butterworth')
xlabel('freq, rads / sec'); 
ylabel('filter response');

% do the same for a higher order filter. 
[B, A] = butter(3, 0.1);
[h, w] = freqz(B,A);
A(2) = A(2) * 0.9;
[h2, ~] = freqz(B,A);
hold on
plot(w,abs(h), 'b')
plot(w,abs(h2), 'r')
title('10% change in one FB filter coef 3rd order butterworth')
xlabel('freq, rads / sec'); 
ylabel('filter response');

The filters show a resonant peak, even though feedback was reduced. Not surprising, really; a lot of systems will show reduced phase margin and will begin to oscillate when poles are moved. Does this mean that a given coefficient (anatomical area) is responsible for resonance? By itself, of course not; one can not extrapolate one effect from one manipulation in a feedback system, especially a higher-order feedback system.

This, of course hold in the mapping of digital (or analog) filters to pathology or anatomy. Pathology is likely reflective of how the loop is structured, not how one element functions (well, maybe).

For a paper, see {1083}

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ref: Hagbarth-1983.02 tags: piper rhythm oscillations feedback proprioception spinal reflex date: 01-19-2012 21:41 gmt revision:2 [1] [0] [head]

PMID-6869036[0] The Piper rhythm--a phenomenon related to muscle resonance characteristics?

  • Piper rhythm: the tendency towards rhytmical 40-60 Hz grouping of motor unit potentials in steadily contracting human muscles.
  • Recording of nerves in muscles did not support the idea that the Piper rhythm is dependent on afferent spindle pulses causing reflex entrainment. (loop too slow).
  • TThis wouldn't make sense anyway, as the same rhythm appears in different muscles with markedly different mechanical properties.
  • Likkely cause is the cerebrum, upper oscillations. Interesting!
  • See also: PMID-9862895[1] Cortical correlate of the Piper rhythm in humans.
    • MEG data is consistent with the cortex being the origin of the Piper rhythm.
  • And PMID-10203308[2] Rhythmical corticomotor communication.
    • The rhythmic modulation may form a tool for efficient driving of motor units but we express some reservations about the assumed binding and attention-related roles of the rolandic brain rhythms.
  • PMID-10622378[3] Cortical drives to human muscle: the Piper and related rhythms.
    • Alternately, oscillations may be a form of holding state.
    • They think gamma frequencies are a means of binding together simultaneously activated isometric muscles.
    • Inadequate output from the basal ganglia leads to a disappearance of the beta and piper drives to muscle.
    • Did we see and piper band osc activity? Did not look.


[0] Hagbarth KE, Jessop J, Eklund G, Wallin EU, The Piper rhythm--a phenomenon related to muscle resonance characteristics?Acta Physiol Scand 117:2, 263-71 (1983 Feb)
[1] Brown P, Salenius S, Rothwell JC, Hari R, Cortical correlate of the Piper rhythm in humans.J Neurophysiol 80:6, 2911-7 (1998 Dec)
[2] Hari R, Salenius S, Rhythmical corticomotor communication.Neuroreport 10:2, R1-10 (1999 Feb 5)
[3] Brown P, Cortical drives to human muscle: the Piper and related rhythms.Prog Neurobiol 60:1, 97-108 (2000 Jan)

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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


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ref: Deco-2009.05 tags: stochastic dynamics Romo memory computation date: 01-16-2012 18:54 gmt revision:1 [0] [head]

PMID-19428958[0] Stochastic dynamics as a principle of brain function

  • Noise produces a 'probabalistic choice'.
  • Used simulated integrate and fire neurons.
  • justification: "and the taking of probabilistic decisions that on an individual trial may be non-optimal, but that may be adaptive by providing evidence about whether the probability of opportunities is changing in the world". So, a broader optimality in an uncertain world?
  • I'm skimming this, but looks like they largely are focused on frequency discrimination tasks.
  • Lots of text.


[0] Deco G, Rolls ET, Romo R, Stochastic dynamics as a principle of brain function.Prog Neurobiol 88:1, 1-16 (2009 May)

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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: 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.


[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.


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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)


[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: 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


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: 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.


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: 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.


[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:


[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: 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: 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.


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.


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ref: Moritz-2008.12 tags: FES BMI Fetz Moritz Perlmutter spinal cord date: 01-08-2012 05:18 gmt revision:1 [0] [head]

PMID-18923392[0] Direct control of paralysed muscles by cortical neurons.

  • FES BMI: route signals around a broken spinal cord.
  • Found that "neurons could control functional stimulation equally well regardless of any prior association to movement". interesting. consistent with previous work. Wonder if I can duplicate this result.
  • Another relatively straightforward (?) paper where most of the difficulty is technology (!!). I mean, what new knowledge was needed to do this? Compare this with the technology that was needed. One of these was very challenging. now, as it come in for my stuff: what does technology let you do? Have to motivate.


[0] Moritz CT, Perlmutter SI, Fetz EE, Direct control of paralysed muscles by cortical neurons.Nature 456:7222, 639-42 (2008 Dec 4)

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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.


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ref: Romo-1998.03 tags: Romo ICMS stimulation discrimination flutter 1998 date: 01-06-2012 23:43 gmt revision:4 [3] [2] [1] [0] [head]

PMID-9537321[0] Somatosensory discrimination based on cortical microstimulation.

  • trained monkeys to discriminate flutter frequencies; showed it generalized to ICMS stimulation, in that they could compare mechanical and electrical frequencies.
  • Electrodes in area 3b of S1.
  • Showed that cortical neurons are entrained to peripheral stimulation freq.


[0] Romo R, Hernández A, Zainos A, Salinas E, Somatosensory discrimination based on cortical microstimulation.Nature 392:6674, 387-90 (1998 Mar 26)

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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.


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: Kim-2006.06 tags: Hyun Kim Carmena Nicolelis continuous shared control gripper BMI date: 01-06-2012 00:20 gmt revision:2 [1] [0] [head]

IEEE-1634510 (pdf) Continuous shared control for stabilizing reaching and grasping with brain-machine interfaces.

  • The pneumatic gripper for picking up objects.
  • 70% brain control, 30% sensor control optimal.
  • Talk about 20Hz nyquist frequency for fast human motor movements, versus the need to smooth and remove noise.
  • Method: proximity sensors
    • collision avoidance 'pain withdrawal'
    • 'infant palmar grasp reflex'
    • Potential field associated with these sensors to implement continuous shared control.
  • Not! online -- used Aurora's data.


Kim, H.K. and Biggs, J. and Schloerb, W. and Carmena, M. and Lebedev, M.A. and Nicolelis, M.A.L. and Srinivasan, M.A. Continuous shared control for stabilizing reaching and grasping with brain-machine interfaces Biomedical Engineering, IEEE Transactions on 53 6 1164 -1173 (2006)

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ref: Kim-2007.08 tags: Hyun Kim muscle activation method BMI model prediction kinarm impedance control date: 01-06-2012 00:19 gmt revision:1 [0] [head]

PMID-17694874[0] The muscle activation method: an approach to impedance control of brain-machine interfaces through a musculoskeletal model of the arm.

  • First BMI that successfully predicted interactions between the arm and a force field.
  • Previous BMIs are used to decode position, velocity, and acceleration, as each of these has been shown to be encoded in the motor cortex
  • Hyun talks about stiff tasks, like writing on paper vs . pliant tasks, like handling an egg; both require a mixture of force and position control.
  • Georgopoulous = velocity; Evarts = Force; Kalaska movement and force in an isometric task; [17-19] = joint dependence;
  • Todorov "On the role of primary motor cortex in arm movement control" [20] = muscle activation, which reproduces Georgouplous and Schwartz ("Direct cortical representation of drawing".
  • Kakei [19] "Muscle movement representations in the primary motor cortex" and Li [23] [1] show neurons correlate with both muscle activations and direction.
  • Argues that MAM is the best way to extract impedance information -- direct readout of impedance requires a supervised BMI to be trained on data where impedance is explicitly measured.
  • linear filter does not generalize to different force fields.
  • algorithm activity highly correlated with recorded EMG.
  • another interesting ref: [26] "Are complex control signals required for human arm movements?"


[0] Kim HK, Carmena JM, Biggs SJ, Hanson TL, Nicolelis MA, Srinivasan MA, The muscle activation method: an approach to impedance control of brain-machine interfaces through a musculoskeletal model of the arm.IEEE Trans Biomed Eng 54:8, 1520-9 (2007 Aug)
[1] Li CS, Padoa-Schioppa C, Bizzi E, Neuronal correlates of motor performance and motor learning in the primary motor cortex of monkeys adapting to an external force field.Neuron 30:2, 593-607 (2001 May)

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ref: Fagg-2007.1 tags: BMI kinarm Hatsopoulos Moxon Miller FES date: 01-06-2012 00:17 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-17978021[0] Biomimetic Brain Machine Interfaces for the Control of Movement.

  • images/482_1.pdf
  • describe structured models that include arm information & 'plant' dynamics.
    • current methods ignore the dynamics of the musculoskeletal system. Want to mimic natural arm movement.
    • To this end used a kinarm with a paralyzed monkey.
  • obtained real-time prediction of joint force, torque, and EMG
    • Concerning quality of prediction: they use fraction of movement variance that can be accounted for (FVAF) which, though google does not seem to know much about it, is probably the same as R^2. but it does not look that great:
      • 0.61 - 0.65 for torque prediction
      • 0.70 - 0.75 for EMG prediction once again, the limitation is the recording technology.
  • tested coupling predictions to the freehand FES system - see this crazy news brief
  • want to incorporate somatosensory feedback into the BMI.
  • they reference a paper from 2008 - huh? The document claims to be written/published in 2007.


[0] Fagg AH, Hatsopoulos NG, de Lafuente V, Moxon KA, Nemati S, Rebesco JM, Romo R, Solla SA, Reimer J, Tkach D, Pohlmeyer EA, Miller LE, Biomimetic brain machine interfaces for the control of movement.J Neurosci 27:44, 11842-6 (2007 Oct 31)

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ref: notes-2007 tags: clementine BMI robot kinarm timarm 032807 date: 01-06-2012 00:07 gmt revision:14 [13] [12] [11] [10] [9] [8] [head]

  1. http://m8ta.com/tim/clementine.MOV -- opens with totem, MJPG compressor.
  2. http://m8ta.com/tim/timarm_servocontroller.JPG
  3. http://m8ta.com/tim/images/spikeInformation_shuffled.jpg
    1. shuffled information distribution -- high significance level ;)
  4. kinarm.
    1. http://www.hardcarve.com/tim/kinarm.JPG
    2. http://www.hardcarve.com/tim/kinarm2.JPG
    3. http://www.hardcarve.com/tim/kinarm3.JPG
  5. robot svg or timarm png
    1. http://www.hardcarve.com/tim/timarm/timarm_side.jpg
    2. http://m8ta.com/tim/robotPulleyDetail.png
  6. bmi predictions clem 032807
      1. x & y predictions
      1. x & y predictions
      1. z velocity predictions - pretty darn good, snr 2
    1. Movie of the day: http://m8ta.com/tim/clem032807_3dBMI.MPG
      1. cells for that day - 40 in all

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ref: Jones-1992.01 tags: Utah MEA original date: 01-05-2012 22:08 gmt revision:2 [1] [0] [head]

PMID-1510294[0] A Glass/silicon Composite Intracortical Electrode Array.

  • Describe fabrication of the Utah probe.
  • Needles 1.5mm long, 80um in diameter at the base, tapered.
  • 10 x 10 array on 400um spacing.
  • Impedance 10T ohm, capacitance 50fF
  • Old array used diamond dicing saw.
    • electrodes were isolated via p-n-p junctions, formed via thermomigration.
    • Too clever! These electrodes leaked & had poor yield.
  • New method: melt glass into shallow saw kerfs on the backside of a p-doped 1.83mm thick wafer, then remove much of the silicon from the top using the same saw. This produces columns of silicon held together at the base by glass.
    • Diamond dicing saw has a kerf of 50um. These things sound awesome.
    • Photopatterned aluminum electrode lands on the back.
    • Points are made by an acid etch.
    • Then plated in metal of some sort
    • Followed by polymide insulation (3-6um thick) (rather round from the SEM).
    • DC resistance of 10 to 20k.


[0] Jones KE, Campbell PK, Normann RA, A glass/silicon composite intracortical electrode array.Ann Biomed Eng 20:4, 423-37 (1992)

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ref: 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!


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"


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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: Lilly-1950 tags: Lilly original MEA glass pipette date: 01-04-2012 01:52 gmt revision:4 [3] [2] [1] [0] [head]

bibtex:Lilly-1950 A Method of Recording the Moving Electrical Potential Gradients in the Brain. The 25-Channel Bavatron and Electro-Iconograms.

  • images/1017_2.pdf
  • Every cell in the cortex is within 25 um of a capillary (!). Really?
  • You can already see him wanting to record from whales / dolphins.
  • Used electrode arrays and photocathode tubes to record from cat.
  • 8x8mm array, 2mm spacing, 100um tip opening in the glass pipettes.
    • Pipettes could slide up & down to rest gently on the pia.
    • Were filled via capilary action
    • Both acute and chronic recording.
  • 1mm spacing of electrodes would still record on the order of 5,000 neurons; good thing there is exponential space dependence.
    • Resistance 50k, low so that thermal noise has little effect.
  • recorded 3,500 feet of film (!!); 1,200 feet of film accumulates in two minutes; this takes 48 minutes to see once.
  • Results in preparation ... were they ever published? where? Must have been nearly impossible to analyze without a computer!

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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


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.


[0] Hubel DH, Tungsten Microelectrode for Recording from Single Units.Science 125:3247, 549-50 (1957 Mar 22)

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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.


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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..)


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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.


[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.


[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. (!!!)


[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: 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.


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: 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.


[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: Bengtsson-2006.01 tags: inferior olive anatomy date: 01-03-2012 02:49 gmt revision:2 [1] [0] [head]


  • source of long-latency climbing fibers
  • projects to contralateral cerebellum.
  • destruction of IO = destruction of contralateral cerebellum.
  • conversely, removal of one cerebellar hemesphere -> atropy of contralateral IO.
  • the climbing fibers of the IO run through the inferior cerebellar peduncle.
  • according to {115}, the motor cortex projects to the inferior olive. from wikipedia: many collaterals from the reticular formation and from the pyramides enter the inferior olivary nucleus.
  • PMID-16527758 the afferents from the DCN to the IO are involved in feedback control of learning & feedback control of complex/simple spike activity in purkinje cells.
  • PMID-5967023 Afferent connexions to single units in the inferior olive of the cat
    • the immediate response to stimulation of the limb nerves was always excitation of the olivary units, sometimes which was followed by a slent period of inhibition.
    • single units in the olive could be excited by moving single hairs on the foot or be stroking the surface of the limbs.
    • stimulation of the ipsilateral caudate nucleus caused firing in IO units with a latency of 1.0 20ms
  • PMID-5340538 http://hardm.ath.cx:88/pdf/AfferentsInferiorOlive1967.pdf
    • there seem to be two classes of olive units: those that respond with low latency to motor cortex stimulation and spinal pathways (these have a high degree of topographic specificity), and those which respond with higher latency to stimulation of the caudate (with lower topographic specificity).
    • climbing fibers fire more of a wave than an isolated AP.
  • red nucleus and VA/VL thalamus are innervated from the deep cerebellar nuclei, which is inhibited by purkinje cells.

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ref: -0 tags: LDA myopen linear discriminant analysis classification date: 01-03-2012 02:36 gmt revision:2 [1] [0] [head]

How does LDA (Linear discriminant analysis) work?

It works by projecting data points onto a series of planes, one per class of output, and then deciding based which projection plane is the largest.

Below, to the left is a top-view of this projection with 9 different classes of 2D data each in a different color. Right is a size 3D view of the projection - note the surfaces seem to form a parabola.

Here is the matlab code that computes the LDA (from myopen's ceven

% TrainData and TrainClass are inputs, column major here.
% (observations on columns)
N = size(TrainData,1);
Ptrain = size(TrainData,2);
Ptest = size(TestData,2);

% add a bit of interpolating noise to the data.
sc = std(TrainData(:)); 
TrainData =  TrainData + sc./1000.*randn(size(TrainData));

K = max(TrainClass); % number of classes.

%%-- Compute the means and the pooled covariance matrix --%%
C = zeros(N,N);
for l = 1:K;
	idx = find(TrainClass==l);
		% measure the mean per class
	Mi(:,l) = mean(TrainData(:,idx)')';
		% sum all covariance matrices per class
	C = C + cov((TrainData(:,idx)-Mi(:,l)*ones(1,length(idx)))');

C = C./K; % turn sum into average covariance matrix
Pphi = 1/K;
Cinv = inv(C);

%%-- Compute the LDA weights --%%
for i = 1:K
	Wg(:,i) = Cinv*Mi(:,i);
		% this is the slope of the plane
	Cg(:,i) = -1/2*Mi(:,i)'*Cinv*Mi(:,i) + log(Pphi)';
		% and this, the origin-intersect.

%%-- Compute the decision functions --%%
Atr = TrainData'*Wg + ones(Ptrain,1)*Cg;
	% see - just a simple linear function! 
Ate = TestData'*Wg + ones(Ptest,1)*Cg;

errtr = 0;
AAtr = compet(Atr');
	% this compet function returns a sparse matrix with a 1
	% in the position of the largest element per row. 
	% convert to indices with vec2ind, below. 
TrainPredict = vec2ind(AAtr);
errtr = errtr + sum(sum(abs(AAtr-ind2vec(TrainClass))))/2;
netr = errtr/Ptrain;
PeTrain = 1-netr;

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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.


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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.


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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 ...


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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.


[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: Cho-2007.03 tags: SOM self organizing maps Prinicpe neural signal reconstruction recording compression date: 01-03-2012 00:59 gmt revision:2 [1] [0] [head]

PMID-17234384[0] Self-organizing maps with dynamic learning for signal reconstruction.

  • They use a dynamically-learning self-organizing map to compress (encode) continuous neural signals so they can be sent over a wireless link. In this way, you do not have to sort and bin on the device (but this is relatively easy; it seems that their SOM is more computationally expensive than simple thresholding.) Nonetheless, it is an interesting approach.


[0] Cho J, Paiva AR, Kim SP, Sanchez JC, Príncipe JC, Self-organizing maps with dynamic learning for signal reconstruction.Neural Netw 20:2, 274-84 (2007 Mar)

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ref: Wilson-1993.08 tags: Wilson McNaughton 1993 sleep hippocampus array recording date: 01-03-2012 00:57 gmt revision:2 [1] [0] [head]

PMID-8351520[0] Dynamics of the hippocampal ensemble code for space.

  • 73-148 neurons.
  • Could accurately decode the rat's movement through space.
  • "The parallel recording methods outlined here make possible the study of the dynamics of neuronal interactions during unique behavioral events."

PMID-8036517[1] Reactivation of hippocampal ensemble memories during sleep.

  • "Information acquired during active behavior is thus re-expressed in hippocampal circuits during sleep, as postulated by some theories of memory consolidation."


[0] Wilson MA, McNaughton BL, Dynamics of the hippocampal ensemble code for space.Science 261:5124, 1055-8 (1993 Aug 20)
[1] Wilson MA, McNaughton BL, Reactivation of hippocampal ensemble memories during sleep.Science 265:5172, 676-9 (1994 Jul 29)

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ref: Sodagar-2006.31 tags: Najafi michigan probe silicon recording 2006 date: 01-03-2012 00:56 gmt revision:5 [4] [3] [2] [1] [0] [head]

IEEE-4463150 (pdf) A neural signal processor for an implantable multi-channel cortical recording microsystem

  • Full 64 ch NPU (neural processing unit). The 'competition'.
    • Scan mode: all 64 channels are searched for the occurence of neural spikes. Addresses with neural activity are sorted, packed, and sent to the outside world.
      • Each channel can be individually set to +, -, or +- spikes. (no templates).
    • monitor mode: 2 channels of broadband transmission.
  • ref [3] claims 100 channels integrated.
  • inductive bidirectional wireless link.
  • Hierarchical design: 64 channels = 2 32 channel master/slave NPUs, each 4 8-channel modules.
  • External 8-bit A/D converter.
  • One 32-ch NPU in 0.5um AMI N-well CMOS process, 3.5mm x 2.7mm.
  • channel scan rate 64ksample/sec; 64 kspikes/sec, typical 8:1 data compression.
  • 2mbps output rate.
  • see also {393} and {149} - they report the same results, perhaps in more detail.


Sodagar, A.M. and Wise, K.D. and Najafi, K. Engineering in Medicine and Biology Society, 2006. EMBS '06. 28th Annual International Conference of the IEEE 5900 -5903 (2006)

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ref: Gregory-2009.09 tags: wireless recording FM modulation COTS Najafi date: 01-03-2012 00:56 gmt revision:3 [2] [1] [0] [head]

IEEE-5335132 (pdf) Low-cost wireless neural recording system and software

  • COTS design, using the USRP!
    • have a bootable Fedora system with the client s/w. I should do this as well.
  • 15-channel FM transmitter
  • only 6.3g
  • Only 10mW!
  • 24 hour transmission over a range of 3m
  • 25uV in-vivo noise floor.
  • about 2% cross-talk, due to limited b/w.
  • Parts:
    • AD8609 input amplifier (50uA/amp). Only 2 poles high a lowpass (?)
    • ADG706 Mux (low sw power, 1.8V supply)
    • MSP430F20xx uC
    • AD8541 mux buffer into VCO -- 1Mhz b/w, 45ua/amplifier.
    • MAX2608 VCO. No PA required. 6-pin SOT23.
  • Much lighter design than mine. Perhaps not so much filtering is required??


Gregory, J.A. and Borna, A. and Roy, S. and Xiaoqin Wang and Lewandowski, B. and Schmidt, M. and Najafi, K. Engineering in Medicine and Biology Society, 2009. EMBC 2009. Annual International Conference of the IEEE 3833 -3836 (2009)

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ref: Ghovanloo-2005.01 tags: Najafi microstimulation Ghovanloo date: 01-02-2012 03:06 gmt revision:2 [1] [0] [head]

PMID-15651568[0] A compact large voltage-compliance high output-impedance programmable current source for implantable microstimulators.

  • from NCSU - reprazent!
  • (from abtract:) "A new CMOS current source is described for biomedical implantable microstimulator applications, which utilizes MOS transistors in deep triode region as linearized voltage controlled resistors (VCR)."


[0] Ghovanloo M, Najafi K, A compact large voltage-compliance high output-impedance programmable current source for implantable microstimulators.IEEE Trans Biomed Eng 52:1, 97-105 (2005 Jan)

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ref: Akin-1995.06 tags: Najafi neural recording technology micromachined digital TETS 1995 PNS schematics date: 01-01-2012 20:23 gmt revision:8 [7] [6] [5] [4] [3] [2] [head]

IEEE-717081 (pdf) An Implantable Multichannel Digital neural recording system for a micromachined sieve electrode

  • Later pub: IEEE-654942 (pdf) -- apparently putting on-chip isolated diodes is a difficult task.
  • 90mw of power @ 5V, 4x4mm of area (!!)
  • targeted for regenerated peripheral neurons grown through a micromachined silicon sieve electrode.
    • PNS nerves are deliberately severed and allowed to regrow through the sieve.
  • 8bit low-power current-mode ADC. seems like a clever design to me - though I can't really follow the operation from the description written there.
  • class e transmitter amplifier.
  • 3um BiCMOS process. (you get vertical BJTs and Zener diodes)
  • has excellent schematics. - including the voltage regulator, envelop detector & ADC.
  • most of the power is dissipated in the voltage regulator (!!) - 80mW of 90mW.
  • tiny!
  • rather than using pseudoresistors, they use diode-capacitor input filter which avoids the need for chopping or off-chip hybrid components.
  • can record from any two of 32 input channels. I think the multiplexer is after the preamp - right?


Akin, T. and Najafi, K. and Bradley, R.M. Solid-State Sensors and Actuators, 1995 and Eurosensors IX.. Transducers '95. The 8th International Conference on 1 51 -54 (1995)

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ref: Carmena-2005.11 tags: carmena BMI nicolelis single-unit variability 2005 date: 01-01-2012 17:31 gmt revision:2 [1] [0] [head]

PMID-16291944[0] Stable ensemble performance with single-neuron variability during reaching movements in primates.

  • correlation between the firing of single neurons and movement parameters was nonstationary over 30-60 minute recording sessions.
  • yet! you could get stable prediction of arm movements, suggesting that movement parameters are redundantly encoded.
  • this, in turn, implies that you do not need a stable recorded population for good predictions.
  • suggest that the variance itself could be a means of neuronal 'computation' or exploration based on perturbations.
    • later Carmena papers do not mention this.


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

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

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


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

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ref: Thevathasan-2010.04 tags: DCS DBS spinal cord stimulation PD date: 12-28-2011 20:43 gmt revision:4 [3] [2] [1] [0] [head]

PMID-20404313[0] Spinal cord stimulation failed to relieve akinesia or restore locomotion in Parkinson disease.

  • motivated by [1]
  • Implanted two PD patients with commercial DBS stimulators and electrodes; observed no therapeutic effect.
  • Electric field was axial rather than transverse, hence likely did not activate the same way or same ammount as in the Nicolelis study.
  • Not sure if anyone has tried with other eletrodes... spinal cord stimulation would be great for inductive powering.


[0] Thevathasan W, Mazzone P, Jha A, Djamshidian A, Dileone M, Di Lazzaro V, Brown P, Spinal cord stimulation failed to relieve akinesia or restore locomotion in Parkinson disease.Neurology 74:16, 1325-7 (2010 Apr 20)
[1] Fuentes R, Petersson P, Siesser WB, Caron MG, Nicolelis MA, Spinal cord stimulation restores locomotion in animal models of Parkinson's disease.Science 323:5921, 1578-82 (2009 Mar 20)

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ref: -0 tags: M1 Evarts PTN conduction velocity monkey electrophysiology spinal cord date: 12-25-2011 04:25 gmt revision:0 [head]

PMID-14283057 Relation of Discharge Frequency to conduction velocity in pyramidal tract neurons

  • Not all PTN arise from the giant Betz cells -- there are too many pyramical tract axons, and not enough betz cells.
  • Most axons come from smaller cortical neurons [8,11,12].
  • Large cells have large axons hence the highest conduction velocity. (cite the squid studies...)
  • Estimate conduction velocity my stimulating in the medullary pyramid (e.g. the pyramidal tract at the level of the medulla)
  • Conduction velocity, in m/s, is six times diameter in microns (roughly; he lists no source here)
  • Mean frequency for 28 rapidly conductin units was 4.1 Hz;
    • These had a non-moving FR of fractional Hz.
    • Showed bursts with sleep, a few spikes when drowsy, very quiet when not moving.
  • MFR for 34 slower cells was 15.6 Hz.
    • Resting rate was higher in these cells.
    • Also showed bursts / more irregular firing with sleep.
  • Amazingly clean recordings. envy.
  • Some cells have much more irregular / more
  • Brookhart [2] concluded that large, rapidly conducting pyramidal fibers are probably responsible for the phasic element of movement control, whereas the smaller slower neurons are responsible for the tonic element.
  • Also true in the spinal cord: large afferents of the nuclear bag fibers in the muscle spindle carry transient info; group II are smaller and carry steady-state info.
  • ref Mountcastle [14] regarding reciprocal pairs of neurons being (surprise) reciprocally activated during joint movements.

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ref: Laubach-2003.03 tags: cluster matlab linux neurophysiology recording on-line data_analysis microstimulation nicolelis laubach date: 12-17-2011 00:38 gmt revision:4 [3] [2] [1] [0] [head]

IEEE-1215970 (pdf)

  • 2003
  • M. Laubach
  • Random Forests - what are these?
  • was this ever used??

follow up paper: http://spikelab.jbpierce.org/Publications/LaubachEMBS2003.pdf

  • discriminant pusuit algorithm & local regression basis (again what are these? lead me to find the lazy learning package: http://iridia.ulb.ac.be/~lazy/


Laubach, M. and Arieh, Y. and Luczak, A. and Oh, J. and Xu, Y. Bioengineering Conference, 2003 IEEE 29th Annual, Proceedings of 17 - 18 (2003.03)

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ref: Patil-2004.07 tags: BMI DBS Parag Patil Carmena Turner date: 12-14-2011 23:45 gmt revision:4 [3] [2] [1] [0] [head]

PMID-15214971[0] Ensemble recordings of human subcortical neurons as a source of motor control signals for a brain-machine interface

  • they do not show ISI or autocorrelations functions for any of the neurons. however, some of the continuous recordings look really *excellent*.
  • there are a lot of comments at the end of the paper, may which are quite intelligent & informative.
    • motor control becomes defocused in Parkinsons, e.g. too many motor units respond to a movement. This is reduced with the use of dopamine agonists like atrophine.
  • Parag Patil's Homepage


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ref: OReilly-2006.02 tags: computational model prefrontal_cortex basal_ganglia date: 12-07-2011 04:11 gmt revision:1 [0] [head]

PMID-16378516[0] Making Working Memory Work: A Computational Model of Learning in the Prefrontal Cortex and Basal Ganglia

found via: http://www.citeulike.org/tag/basal-ganglia


[0] O'Reilly RC, Frank MJ, Making working memory work: a computational model of learning in the prefrontal cortex and basal ganglia.Neural Comput 18:2, 283-328 (2006 Feb)

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ref: Kemp-1971.09 tags: globus pallidus striatum 1971 neuroanatomy date: 12-07-2011 04:03 gmt revision:1 [0] [head]

PMID-4399123[0] The connexions of the striatum and globus pallidus: synthesis and speculation. !! great figures, great synthesis !!

  • a striking feature of the striatum (caudate and putamen, functionally the same is the dense axonal plexus - this receives a major contribution from the contralateral branches the short axon terminals (interneurons) as well as afferent projections. perhaps the most important characteristic of the axonal plexus is that all the component fibers cross dendrites rather than lie parallel to them -- just like the cerebellum''.
  • the cerebellum also has excitatory input and inhibitory output. similar structure to do a similar thing? ++ plenty of interneurons ++plenty of dendritic spines.
  • all of the cerebral cortex projects to the cerebellum, even the visual cortex has projections to the pontine nuclei. however, there is an exceptionallly small projection from the visual cortex to both the cerebellum and striatum.


[0] Kemp JM, Powell TP, The connexions of the striatum and globus pallidus: synthesis and speculation.Philos Trans R Soc Lond B Biol Sci 262:845, 441-57 (1971 Sep 30)

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ref: Harris-2008.03 tags: retroaxonal retrosynaptic Harris learning cortex backprop date: 12-07-2011 02:34 gmt revision:2 [1] [0] [head]

PMID-18255165[0] Stability of the fittest: organizing learning through retroaxonal signals

  • the central hypothesis: strengthening of a neuron's output synapses stabilizes recent changes in the same neuron's inputs.
    • this causes representations (as are arrived at with backprop) that are tuned to task features.
  • Retroaxonal signaling in the brain is too slow for an instructive (says at least the sign of the error wrt a current neuron's output) backprop algorithm
  • hence, retroaxonal signals are not instructive but selective.
  • At SFN Harris was looking for people to test this in a model; as (yet) unmodeled and untested, I'm suspicious of it.
  • Seems plausible, yet it also just seems to be a way of moving the responsibility for learning computation to the postsynaptic neuron (which is then propagated back to the present neuron). The theory does not immediately suggest what neurons are doing to learn their stuff; rather how they may be learning.
    • If this stabilization is based on some sort of feedback (attention? reward?), which may guide learning (except for the cortex, which does not have many (any?) DA receptors...), then I may be more willing to accept it.
    • It seems likely that the cortex is doing a lot of unsupervised learning: predicting what sensory info will come next based on present sensory info (ICA, PCA).


[0] Harris KD, Stability of the fittest: organizing learning through retroaxonal signals.Trends Neurosci 31:3, 130-6 (2008 Mar)

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ref: Gandolfo-2000.02 tags: Gandolfo Bizzi dynamic environment force fields learning motor control MIT M1 date: 12-02-2011 00:10 gmt revision:1 [0] [head]

PMID-10681435 Cortical correlates of learning in monkey adapting to a new dynamical environment.

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ref: -0 tags: story falls lake journal mexican coincidence date: 08-18-2011 17:32 gmt revision:2 [1] [0] [head]

I'm an avid open-water swimmer, and other than the quarry and beach, I spend many fridays hoping the water in Falls lake is not too choppy. If it's glassy and smooth (and even sometimes when it's not), I can fall into the hypnotic 4/4 chug of stroke-stroke-stroke-breathe, stroke-str ... not hard, since the brown water is featureless, and the above-water scenery doesn't change much either.

Several years ago I was out on Falls lake doing my thing, comfortably clear in the middle of the lake, heading back to the beach. In my unawareness I failed to notice that a thunderstorm had grown in the hot summer afternoon. Normally I'm rather debonaire about these things, but have been in places just before they were struck by lightning, and this felt a little like that.

So, SOL Tim starts considering the rather limited options (god) (hold breath for as long as possible) (are they the same?). Just then, some Mexican guy on a kayak comes paddling out of ... nowhere ... and asks me if I need help. I bearhug the back of his boat and we get back to shore before the storm breaks. .... Another friday, another season and I set off with a friend clear across Falls lake, which is far, like 3mi round trip. I chat with a Mexican dude before we launch the ships; i guess he seems a bit familiar, but I'm too nervous, eager, and worrying about the thoughts/abilities of my friend to think much. That swim goes fine, minus all the damned speadboats and the ravenous hunger that sets in afterward.

Yesterday I had intended to swim at a pool, but some toddling kid chose to contaminate it, and so back to Falls Lake. It's choppy and hard to swim, and I don't make it as far as intended; again before launching, I meet a Mexican dude, and he asks me if I'm crossing the lake again. I tell him no, not enough time; the water envelops, and I'm back in the swim coma, gone to the point when I get back the sun is down and the moon has risen.

Surprisingly, when I get back the Mexican guy and his family are still there, slowly cleaning up BBQ debris by the light of highbeams and one crappy flashlight. It's cool and peaceful on the lake, but they probably should have left half an hour ago; as I go to the restroom to change, I wave to the guy and realize two things simultaneously: (1) fuck, it's been the same guy, (2) he may have delayed departure, gracefully and surreptitiously, until I was back. Curiosity makes me want to ask if he had, to see if coincidence licked me again, but that's not right; I did't.

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ref: -0 tags: hike Culbreth North Carolina date: 02-07-2011 04:44 gmt revision:2 [1] [0] [head]

Excellent hike with So-- and Vi-- today. We somehow completely overshot the original southward path toward the car @ ~ 5:30-5:45 (marked with 'oops' on the map). In our race against the falling sun we continued too far west, ultimately all the way to Uzzle Rd; hence we had to return for a good number of miles on the road under the cooling night sky. Gorgeous country; the hill in that area is even 'large' (740') for Piedmont standards, and affords a view of the farms.

for S & V: the hill we saw from the top is right by Pyrophyllite Lake 3 miles south of the lookout point. Total hike distance was 9.5 miles.

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ref: -0 tags: evolutionary psychology human mating sexuality discrimination wedlock date: 01-09-2011 18:22 gmt revision:1 [0] [head]

From Why Beautiful people have more daughters:

"Abuse, degradation, and intimidation are all part of men's unfortunate repertoire of tactics employed in competitive situations. In other words, men are not harassing women because they are treating them differently than men (which is the definition of discrimination under which harassment legally falls), but the exact opposite: men harass women because they are not discriminating between men and women."

Interesting argument. But in sexual discrimination cases, the women are not being treated the way they want to be treated - this is more a problem than the inequality.

The author then goes on to pose that current sexual discrimination law and policy in US corporations actually inhibits welcome sexual/romantic interest/advances. Many people do find partners at work. Again, I beg to differ: if there is passion between people, things will fall as they should; if policy and culture serves to make this more civilized (provided it's not completely inhibited, as the author suggests), then all the better.

In related news: An Analysis of Out-Of-Wedlock Births in the United States

Central hypothesis: Contraceptive technology shifted the balance of power between the sexes: prior the pill, women could force the men into promising to marry; in the case of preganancy, cultural standards forced marriage - shotgun marriage. Men accepted these terms because they were uniform across all women - sex implies pregnancy implies child rearing. When contraception became available, this was decoupled, as sex did not beget pregnancy; those women who negotiated on the old terms were likely to lose their mate, hence shotgun marriages (the result of such negotiations) gradually disappeared from culture.

The author generally approves of the idea of shotgun marriage, and suggests that a governmental body should enforce a form of it through child support payments. Presently about 40% of children in the US are born out of wedlock.

Finally, Serial monogamy increases reproductive success in men but not in women. It rests upon data, only recently gathered, that supports that having multiple partners increases reproductive success more strongly in male than in female humans. This implies that the variance of the fertility of men should be higher than that of women - again, which is borne out in the data, but only weakly: men have 10% higher variance in # of offspring than women. This effect is correlated to serial monogamy - "Compared with men with 1 spouse, men with 3 or more spouses had 19% more children in the total sample". This did not hold with women, nor did varying spouse number in men change the survival rate of their offspring.

Irregardless, this reading was spurred by someone mentioning that a genetic analysis of human populations reveals that while 80% of women reached reproductive success, only 40% of men did - implying that historically a few more successful men fathered a large fraction of children. I was unable to find evidence to support this on the internet (and indeed the Behavioral Ecology article gives much less dramatic figures), but it makes intuitive sense, especially in light of some patterns of male behavior.

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ref: ai-0 tags: automatic programming journal notes date: 12-31-2010 05:24 gmt revision:4 [3] [2] [1] [0] [head]

This evening, on the drive back from wacky (and difficult) Russian-style yoga, I got a chance to explain to my brother what I really want to be working on, the thing that really tickles my fancy. My brother and I, so much as genetic commonality and common upbringing seem to effect, have very similar styles of thinking, which made explaining things a bit easier. For you, dear readier, I'll expand a bit.

I'd like to write a program that writes other programs, iteratively, given some objective function / problem statement / environment in which to interact. The present concrete goal is to have a said program make a program that is able to lay out PCBs with quality similar to that of humans. The overarching framework that I'm planning on using is genetic/evolutionary algorithms (the latter does not have crossover, fyi), but no one has applied GA to the problem in this way: most people use GA to solve a particular instance of a problem. Rubbish, i say, this is energy wasteful!

Rubbish, you may return: the stated problem requires a degree of generalization and disconnect from the 'real world' (the PCB) that makes GAs extremely unlikely to come up with any solutions. Expressed another way: the space to be explored is too large (program begets program begets solution). This is a very sensible critique; there is no way in hell a GA can solve this problem. They are notably pathetic at exploring space in a energy-efficient way (to conclude a paragraph again with energy... ).

There are known solutions for this: memory -- cache the results, in terms of algorithm & behavior, of all 'hypotheses' or individuals tried out by a GA. This is what humans do -- they remember the results of their experiment, and substitute the result rather than running a test again. But humans do something far more sophisticated and interesting than just memory - they engineer systems; engineering is an iterative process that often goes down wrong design paths, yet it nonetheless delivers awesome things like Saabs and such.

As I described to K--, engineering is not magic and can be (has been?) described mechanistically. First of all, most engineering artifacts start off from established, well-characterized components, aggregated through the panoply of history. Some of these components describe how other components are put together, things that are either learned in school or by taking things apart. Every engineer, ala Newton, stands on the vast shoulders of the designers before; hence any program must also have these shoulders available. The components are assembled into a system in a seemingly ad-hoc and iterative procedure: sometimes you don't know what you want, so you play with the parts sorta randomly, and see what interesting stuff comes out. Other times you know damn well what you / your boss / the evil warlord who holds you captive wants. Both modes are interesting (and the dichotomy is artificial), but the latter is more computer-like, hence to be modeled.

Often the full details of the objective function or desired goal is very unclear in the hands of the boss / evil warlord (1), despite how reluctant they may be to admit this. Such an effect is well documented in Fred Brooks' book, __The Design of Design__. Likewise, how to get to a solution is unclear in the mind of an engineer, so he/she shuffles things around in the mind (2),

  1. looking for components that deliver particular desired features (e.g. in an electronic system, gain makes me think of an op-amp)
  2. looking for components that remove undesirable features (e.g. a recent noise problem on my wireless headstage made me think of a adaptive decorrelating filter I made once)
  3. looking for transforms that make the problem solvable in a linear space, something that Moshe Looks calls knob-twiddling.
    1. this is from both sides -- transforms that convert the problem or the nascent solution.
    2. An example would be the FFT. This makes it easy to see spectral features.
    3. Another example, used even more recently, is coordinate transforms - it makes thinks like line-line intersection much easier.
    4. When this doesn't work, you can do far more powerful automatic coordinate transform - math, calculus. This is ultimately what I needed when figuring out the shortest line segment between a line segment and a ellipse. Don't ask.

This search is applied iteratively, apparently a good bit of the time subconsciously. A component exists in our mind as a predictive model of how the thing behaves, so we simulate it on input, observe output, and check to see if anything there is correlated / decorrelated with target features. (One would imagine that our general purpose modeling ability grew from needing to model and predict the world and all the yummy food/dangerous animals/warlords in it). The bigger the number of internal models in the engineers mind, the bigger the engineers passion for the project, the more components can be simulated and selected for. Eventually progress is made, and a new subproblem is attacked in the same way, with a shorter path and different input/output to model/regress against.

This is very non-magical, which may appall the more intuitive designers among us. It is also a real issue, because it doesn't (or poorly) explains really interesting engineering: e.g. the creation of the Fourier transform, the creation of the expectation-maximization algorithm, all the statistical and mathematical hardware that lends beauty and power to our design lives. When humans create these things, they are at the height of their creative ability, and thus it's probably a bit ridiculous to propose having a computer program do the same. That does not prevent me from poking at the mystery here, though: perhaps it is something akin to random component assembly (and these must be well known components (highly accurate, fast internal models); most all innovations were done by people exceptionally familiar with their territory), with verification against similarly intimately known data (hence, all things in memory - fast 'iteration cycles'). This is not dissimilar to evolutionary approaches to deriving laws. A Cornell physicist / computer scientist was able to generate natural laws via a calculus-infused GA {842}, and other programs were able to derive Copernicus' laws from planetary data. Most interesting scientific formulae are short, which makes them accessible to GAs (and also aesthetically pleasurable, and/or memelike, but hey!). In contrast engineering has many important design patterns that are borrowed by analogy from real-world phenomena, such as the watermark algorithm, sorting, simulated annealing, the MVC framework, object-oriented programming, WIMP interface, verb/noun interface, programming language, even GAs themselves! Douglas Hofstadter has much more to say about analogies, so I defer to him here.

Irregardless, as K-- pointed out, without some model for creativity (even one as soulless as the one above), any proposed program-creating program will never come up with anything really new. To use a real-world analogy, at his work the boss is extremely crazy - namely, he mistook a circuit breaker for an elevator (in a one-story factory!). But, this boss also comes up with interminable and enthusiastic ideas, which he throws against the wall of his underlings a few dozen times a day. Usually these ideas are crap, but sometimes they are really good, and they stick. According to K--, the way his mind works is basically opaque and illogical (I've met a few of these myself), yet he performs an essential job in the company - he spontaneously creates new ideas. Without such a boss, he claimed, the creations of a program-creating-program will impoverished.

And perhaps hence this should be the first step. Tonight I also learned that at the company (a large medical devices firm) they try to start projects at the most difficult step. That way, projects that are unlikely to succeed are killed as soon as possible. The alternate strategy, which I have previously followed, is to start with the easiest things first, so you get some motivation to continue. Hmm...

The quandary to shuffle your internal models over tonight then, dear readers, is this: is creativity actually (or accurately modeled by) random component-combination creation (boss), followed by a selection/rejection (internal auditing, or colleague auditing)? (3)

  • (1) Are there any beneficent warlords?
  • (2) Yet: as I was educated in a good postmodernist tradition, this set of steps ('cultural software') is not the only way to design. I'm just using it since, well, best to start with something that already works.
  • (3) If anyone reads this and wants to comment, just edit this. Perhaps you want to draw a horizontal line and write comments below it? Anyway, writing is active thinking, so thanks for helping me think.

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ref: -0 tags: science decay truth observation bias Jonah Lehrer new yorker date: 12-20-2010 01:23 gmt revision:3 [2] [1] [0] [head]

"The Truth Wears Off" by Jonah Lehrer, the New Yorker.

  • "The disturbing implication of the Crabbe study is that a lot of extraordinary scientific data are nothing but noise. [...] This suggests that the decline effect is actually a decline of illusion."
  • "The situation is even worse when a subject is fashonable. In recent years, for instance, there have been hundreds of studies on the various genes that control the differences in risk between men and women. These findings have included the mutations responsible for the increased risk of schizophrenia to the genes underlying hypertension. Ioannidis and his colleagues looksed at 432 of these claims. [...] The most troubling fact emerged when he looked at the test of replication: out of four hundred thirty two claims, only a single one was consistently replicatable. "This doesn't mean that none of these claims will turn out to be true," he says. "But, given that most of them were done badly, I wouldn't hold my breath."
  • Some follow up discussion on wired science
  • Synopsis of the sources of this decline:
    • The original data was an outlier; we scientists are biased to look for interesting outliers & report them.
      • The decline is nothing less than a regression to the mean.
    • Scientists have strong observation bias, especially when measuring difficult things, like the length of wing feathers (hypothesis being that symmetrical males mate more, are selected for by the females of their species).
    • Publishers have strong bias; they like to publish positive results.
      • Hell, we humans like/love positive results (what works!) which is good and normal.
    • This is a trace - an 'impulse response' of the feedback system that is science. An idea is a fad for a few years, when other scientists will try to repeat and buttress it (which leads to a strong bias in publishing), then scientists seeking new novelty will attack it. The idea henceforth declines.
  • Anyway, have been thinking this for a while, good to see some evidence (meta-evidence?).
  • cached
  • Richard Feynman quote, courtesy of Joey, which illustrates another side of the coin: "Millikan measured the charge on an electron by an experiment with falling oil drops, and got an answer which we now know not to be quite right. It’s a little bit off, because he had the incorrect value for the viscosity of air. It’s interesting to look at the history of measurements of the charge of the electron, after Millikan. If you plot them as a function of time, you find that one is a little bigger than Millikan’s, and the next one’s a little bit bigger than that, and the next one’s a little bit bigger than that, until finally they settle down to a number which is higher. Why didn’t they discover that the new number was higher right away? It’s a thing that scientists are ashamed of–this history–because it’s apparent that people did things like this: When they got a number that was too high above Millikan’s, they thought something must be wrong–and they would look for and find a reason why something might be wrong. When they got a number closer to Millikan’s value they didn’t look so hard. And so they eliminated the numbers that were too far off, and did other things like that."

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ref: -0 tags: sciences artificial Simon organizations economic rationality date: 12-01-2010 07:33 gmt revision:2 [1] [0] [head]

These are notes from reading Herbert A. Simon’s The Sciences of the Artificial, third edition, 1996 (though most of the material seems from the 70s). They are half quoted / half paraphrased (as needed when the original phrasing was clunky). I’ve added a few of my own observations, and reordered the ideas from the book.

“A large body of evidence shows that human choices are not consistent and transitive, as they would be if a utility function existed ... In general a large gain along one axis is required to compensate for a small loss along another.” HA Simon.

Companies within a capitalist economy make almost negligible use of markets in their internal functioning” - HA Simon. Eg. they are internally command economies. (later, p 40...) We take the frequent movability and indefiniteness of organizational boundaries as evidence that there is often a near balance between the advantages of markets and organizations”

  • Retail sales of automobiles are handled by dealerships
  • Many other commodities are sold directly to the consumer
  • In fast food there are direct outlets and franchises.
  • There are sole source suppliers that produce parts for much larger manufacturers.
I’m realizing / imagining a very flexible system of organizations, tied together and communicating via a liquid ‘blood’ of the market economy.

That said: organizations are not highly centralized structures in which all the important decisions are made at the center; this would exceed the limits of procedural rationality and lose many of the advantages attainable from the use of hierarchical authority. Business organizations, like markets, are vast distributed computers whose decision processes are substantially decentralized. In fact, the work of the head of a corporation is a market-like activity: allocating capital to promising or desirable projects.

In organizations, uncertainty is often a good reason to shift from markets to hierarchies in making decisions. If two different arms of a corporation - production and marketing - make different decisions on the uncertain number of units to be sold next year, there will be a problem. It is better for the management to share assumptions. “Left to the market, this kind of uncertainty leads directly to the dilemmas of rationality that we described earlier in terms of game theory and rational expectations”

I retain vivid memories of the astonishment and disbelief expressed by the architecture students to whom I taught urban land economics many years ago when I pointed to medieval cities as marveluosly patterned systems that had mostly just ‘grown’ in response to myriads of individual human decisions. To my students a pattern implied a planner in whose mind it had been conceived and whose hand it had been implemented. The idea that a city could acquire its patter as naturally as a snowflake was foreign to them ... they reacted to it as many christian fundamentalists responded to Darwin: no design without a Designer!

Markets appear to conserve information and calculation by assigning decisions to actors who can make them on the basis of information that is available to them locally. von Hayek: “The most significant fact about this system is the economy of knowledge with which it operates, o how little the individual participants need to know in order to make the right action”. To maintain actual Pareto optimality in the markets would require information and computational requirements that are exceedingly burdensome and unrealistic (from The New Palgrave: A dictionary of Economics)

Nelson and winter observe that in economic evolution, in contract to biological evolution, sucessful algorithms (business practices) may be borrowed from one firm to the other. The hypothesized system is Lamarkian, because any new idea can be incorporated in opearting procedures as soon as its success is observed" . Also, it's good as corporations don't have secual reproduction / crossover.

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ref: work-0 tags: kinarm problem mathML date: 11-03-2010 16:05 gmt revision:8 [7] [6] [5] [4] [3] [2] [head]

Historical notes from using the Kinarm... this only seems to render properly in firefox / mozilla.

To apply cartesian force fields to the arm, the original kinarm PLCC (whatever that stands for) converted joint velocities to cartesian veolocities using the jacobian matrix. All well and good. The equation for endpoint location of the kinarm is:

x^=[l 1sin(θ sho)+l 2sin(θ sho+θ elb) l 1cos(θ sho)+l 2cos(θ sho+θ elb)] \hat{x} = { \left[ \array{ l_1 sin(\theta_{sho}) + l_2 sin(\theta_{sho} + \theta_{elb} ) \\ l_1 cos(\theta_{sho}) + l_2 cos(\theta_{sho} + \theta_{elb} ) } \right] }

L_1 = 0.115 meters, l_2 = 0.195 meters in our case. The jacobian of this function is: J=[l 1sin(θ sho)l 2sin(θ sho+θ elb) l 2sin(θ elb) l 1cos(θ sho)+l 2cos(θ sho+θ elb) l 2cos(θ elb)] J = { \left[ \array{ - l_1 sin(\theta_{sho}) - l_2 sin(\theta_{sho} + \theta_{elb} ) && - l_2 sin(\theta_{elb}) \\ l_1 cos(\theta_{sho}) + l_2 cos(\theta_{sho} + \theta_{elb} ) && l_2 cos(\theta_{elb}) } \right] } v^=Jθ^ \hat{v} = J \cdot \hat{\theta} etc. and (I think!) F^=Jτ^ \hat{F} = J \cdot \hat{\tau} where tau is the shoulder and elbow torques and F is the cartesian force. The flow of the PLCC is then:

  1. convert joint angluar velocities to cartesian velocities
  2. cartesian velocities to cartesian forces by a symmetric matrix A which effects simple viscious and curl fields.
F^=Av^ \hat{F} = A \cdot \hat{v}
  1. cartesian forces to joint torques via the inverse of the jacobian.
But, and I may be wrong here, rather than inverting the jacobian, the PLCC simply takes the transform. The inverse of the jacobian and the transpose are not even close to equal. viz (from mathworld):

J=[a b c d] J = { \left[ \array{ a & b \\ c & d } \right] }

J 1=1adbc[d b c a][a c b d]=J T J^{-1} = \frac{ 1}{a d - b c} { \left[ \array{d &-b \\ -c & a} \right] } \ne { \left[ \array{a & c \\ b & d} \right] } = J^{T}

substitute to see if the matrices look similar ...

|J|[l 2cos(θ elb) l 2sin(θ elb) l 1cos(θ sho)l 2cos(θ sho+θ elb) l 1sin(θ sho)l 2sin(θ sho+θ elb)][l 1sin(θ sho)l 2sin(θ sho+θ elb) l 1cos(θ sho)+l 2cos(θ sho+θ elb) l 2sin(θ elb) l 2cos(θ elb)]{\vert J \vert} \cdot { \left[ \array{ l_2 cos(\theta_{elb}) && l_2 sin(\theta_{elb}) \\ - l_1 cos(\theta_{sho}) - l_2 cos(\theta_{sho} + \theta_{elb} ) && - l_1 sin(\theta_{sho}) - l_2 sin(\theta_{sho} + \theta_{elb} ) } \right] } \ne { \left[ \array{ - l_1 sin(\theta_{sho}) - l_2 sin(\theta_{sho} + \theta_{elb} ) && l_1 cos(\theta_{sho}) + l_2 cos(\theta_{sho} + \theta_{elb} ) \\ - l_2 sin(\theta_{elb}) && l_2 cos(\theta_{elb}) } \right] }


|J|=l 1l 2sin(θ sho)cos(θ elb)l 2 2sin(θ sho+θ elb)cos(θ elb)+l 1l 2cos(θ sho)sin(θ elb)l 2 2cos(θ sho+θ elb)sin(θ elb) {\vert J \vert} = { - l_1 l_2 sin(\theta_sho) cos(\theta_elb) - l_2^2 sin(\theta_{sho} + \theta_{elb} ) cos(\theta_elb) + - l_1 l_2 cos(\theta_sho) sin(\theta_elb) - l_2^2 cos(\theta_{sho} + \theta_{elb} ) sin(\theta_elb) }

I'm surprised that we got something even like curl and viscous forces - the matrices are not similar. This explains why the forces seemed odd and poorly scaled, and why the constants for the viscious and curl fields were so small (the units should have been N/(cm/s) - 1 newton is a reasonable force, and the monkey moves at around 10cm/sec, so the constant should have been 1/10 or so. Instead, we usually put in a value of 0.0005 ! For typical values of the shoulder and elbow angles, the determinant of the matrix is 200 (the kinarm PLCC works in centimeters, not meters), so the transpose has entries ~ 200 x too big. Foolishly we compensated by making the constant (or entries in A) 200 times to small. i.e. 1/10 * 1/200 = 0.0005 :(

The end result is that a density-plot of the space spanned by the cartesian force and velocity is not very clean, as you can see in the picture below. The horizontal line is, of course, when the forces were turned off. A linear relationship between force and velocity should be manifested by a line in these plots - however, there are only suggestions of lines. The null field should have a negative - slope line in upper left and lower right; the curl field should have a positive sloped line in the upper right and negative in the lower left (or vice-vercia).


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ref: -0 tags: meta learning Artificial intelligence competent evolutionary programming Moshe Looks MOSES date: 08-07-2010 16:30 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

Competent Program Evolution

  • An excellent start, excellent good description + meta-description / review of existing literature.
  • He thinks about things in a slightly different way - separates what I call solutions and objective functions "post- and pre-representational levels" (respectively).
  • The thesis focuses on post-representational search/optimization, not pre-representational (though, I believe that both should meet in the middle - eg. pre-representational levels/ objective functions tuned iteratively during post-representational solution creation. This is what a human would do!)
  • The primary difficulty in competent program evolution is the intense non-decomposability of programs: every variable, constant, branch effects the execution of every other little bit.
  • Competent program creation is possible - humans create programs significantly shorter than lookup tables - hence it should be possible to make a program to do the same job.
  • One solution to the problem is representation - formulate the program creation as a set of 'knobs' that can be twiddled (here he means both gradient-descent partial-derivative optimization and simplex or heuristic one-dimensional probabilistic search, of which there are many good algorithms.)
  • pp 27: outline of his MOSES program. Read it for yourself, but looks like:
  • The representation step above "explicitly addresses the underlying (semantic) structure of program space independently of the search for any kind of modularity or problem decomposition."
    • In MOSES, optimization does not operate directly on program space, but rather on subspaces defined by the representation-building process. These subspaces may be considered as being defined by templates assigning values to some of the underlying dimensions (e.g., they restrict the size and shape of any resulting trees).
  • In chapter 3 he examines the properties of the boolean programming space, which is claimed to be a good model of larger/more complicated programming spaces in that:
    • Simpler functions are much more heavily sampled - e.g. he generated 1e6 samples of 100-term boolean functions, then reduced them to minimal form using standard operators. The vast majority of the resultant minimum length (compressed) functions were simple - tautologies or of a few terms.
    • A corollary is that simply increasing syntactic sample length is insufficient for increasing program behavioral complexity / variety.
      • Actually, as random program length increases, the percentage with interesting behaviors decreases due to the structure of the minimum length function distribution.
  • Also tests random perturbations to large boolean formulae (variable replacement/removal, operator swapping) - ~90% of these do nothing.
    • These randomly perturbed programs show a similar structure to above: most of them have very similar behavior to their neighbors; only a few have unique behaviors. makes sense.
    • Run the other way: "syntactic space of large programs is nearly uniform with respect to semantic distance." Semantically similar (boolean) programs are not grouped together.
  • Results somehow seem a let-down: the program does not scale to even moderately large problem spaces. No loops, only functions with conditional evalutation - Jacques Pitrat's results are far more impressive. {815}
    • Seems that, still, there were a lot of meta-knobs to tweak in each implementation. Perhaps this is always the case?
  • My thought: perhaps you can run the optimization not on program representations, but rather program codepaths. He claims that one problem is that behavior is loosely or at worst chaotically related to program structure - which is true - hence optimization on the program itself is very difficult. This is why Moshe runs optimization on the 'knobs' of a representational structure.

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ref: OSuilleabhain-1998.11 tags: analysis tremor parkinsons disease date: 07-19-2010 19:22 gmt revision:2 [1] [0] [head]

PMID-9827772[0] Time-frequency analysis of tremor

  • Frequency of tremor in non-attended, non-tapping leg and arm changed frequency and synchronized:
    • For example, arm and leg tremors at 5.2 and 3.8 Hz, respectively, shifted to a common frequency of 4.6 Hz in one Parkinsons disease patient while using the contralateral arm to perform a tapping movement in time with a metronome at 2 Hz.
    • Psychogneic tremor was sychronized to the metronome in normal volunteers (e.g. 2Hz or 4Hz).
  • PSD was estimated via the welch method of averaging periodograms (FFT length 128, kaiser window segments overlapping 50%)
  • Also used the wigner method for tracking frequency changes in the tremor; this yeilded estimates every 0.5s with 0.1Hz resolution.


[0] O'Suilleabhain PE, Matsumoto JY, Time-frequency analysis of tremors.Brain 121 ( Pt 11)no Issue 2127-34 (1998 Nov)

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ref: work-0 tags: PSD FFT periodogram autocorrelation time series analysis date: 07-19-2010 18:45 gmt revision:3 [2] [1] [0] [head]

Studies in astronomical time series analysis. II - Statistical aspects of spectral analysis of unevenly spaced data Scargle, J. D.

  • The power at a given frequency as computed by a periodigram (FFT is a specific case of the periodigram) of a gaussian white noise source with uniform variance is exponentially distributed: P z(z)=P(x<Z<z+dz)=e zdzP_z(z) = P(x&lt;Z&lt;z+dz) = e^{-z}dz
    • The corresponding CDF: 1e z 1- e^{-z} or P(Z>z)=e zP(Z&gt;z) = e^{-z} which gives the probability of a large observed power at a given freq.
    • If you need to average N samples, then P(Z>z)=1(1e z) NP(Z&gt;z) = 1 - (1-e^{-z})^N where Z=max nPow(ω n)Z = max_n Pow(\omega_n)
  • Means of improving detection using a periodogram:
    • Average in time - this means that N above will be smaller, hence a spectral peak becomes more significant.
      • Cannot average too much - at some point, averaging will start to attenuate the signal!
    • Decrease the number of frequencies inspected.
  • Deals a good bit with non-periodic sampling, which i guess is more common in astronomical data (the experimenter may not take a photo every day, or the same time every day (clouds!).

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ref: work-0 tags: DB Lenat Eurisko date: 07-19-2010 04:37 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

images/824_1.pdf -- Eurisko by DB Lenat, the program that made the fleet which won the 1981 and 1982 Traveller's challenge, as I discovered in this New Yorker article by Malcolm Gladwell.

  • Notable observations of the author: EURISKO'S progress in this domain was entertaining, and a fundamental feature of this domain became clear: large programs are carefully engineered artifacts, complex constructs with thousands of pieces in a kind of unstable equilibrium. Any sort of random perturbation is likely to produce an error rather than a novel mutant. The analogy to biological evolution is strong.
    • EURISKO had successes in automatic programming only when it modified functions which had been coded as units. Why was this?
  • He also tried simulating biological evolution, and found that progress was slow when the mutations were random, but were quite rapid when they were organized by a set of heuristics. Heuristics, in this case, refer to rules like 'fewer defenses require faster legs and better ears and noses' - which can be generalized by simple observations of nature - or 'large cranium requires large female cervical opening' which is a heuristic that has only weakly been encoded in our DNA in the form of mate preference (maybe).
    • Quote: The net effect of having these heuristics for guiding plausible mutations was that, in a single generation, an offspring would emerge with a whole constellation of related mutations that worked together. For example, one had thicker fur, a thicker fat layer, whiter fur, smaller ears, etc. It is not known whether there is any biological validity to this radical hypothesis, but there is no doubt that the simulated evolution progressed almost not at all when mutation was random, and quite rapidly when mutation was under control of a body of heuristic rules. See [10].
    • This is consistent with homeobox genes, which were discovered in 1983. ref
  • The introductory and explicit description of the program was more difficult to parse than the later examples illustrating exactly what Eurisko did/does; the introduction of weakly-weighted contrapositive heuristics to a defeated heuristics on page 90 (page 30 in the pdf), for example, is revealing.
  • Eurisko has a sensible trigger for invoking heuristic / generalizing rules: when a particular node has too many entries (slots, in his terminology), a set of heuristics are called in to segregate the set of entries by common features, e.g. clustering.
  • The conclusion - a list of ideas (heuristics!) regarding the development of his program - is well articulated and useful, even 29 years later! In particular: "In other words, even though the discovery of new heuristics is important, the presence (and maintenance) of an appropriate representation for knowledge is even more necessary." (my emphasis)
  • Again: "Brevity is a key attribute in any kind of asemantic exploration. If useful concepts are short expressions in your language, then you have some chance of coming across them often, even if you don't know much about the terrain."

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ref: notes-0 tags: CSV blog article group dynamics steinberg date: 07-05-2010 15:30 gmt revision:1 [0] [head]

Another excellent post from Steinberg regarding treating people as predictable nonlinear fluids. "The system works far better when a column is introduced off-center in front of the door,as demonstrated Mr. Torrens. "It's counterintuitive, but the column sends shock waves through the crowds to break up the congestion patterns." (...) Most traffic jams are emergent phenomena that begin with mistakes from just one or two drivers. According to Horvitz's models, they can actually "un-jam" traffic by calling drivers at a particular location, and giving them very specific instructions: "Move to the left-most lane, and then speed-up to 65."

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ref: work-0 tags: perl fork read lines external program date: 06-15-2010 18:08 gmt revision:0 [head]

Say you have a program, called from a perl script, that may run for a long time. Get at the program's output as it appears?

Simple - open a pipe to the programs STDOUT. See http://docstore.mik.ua/orelly/perl/prog3/ch16_03.htm Below is an example - I wanted to see the output of programs run, for convenience, from a perl script (didn't want to have to remember - or get wrong - all the command line arguments for each).


$numArgs = $#ARGV + 1;
if($numArgs == 1){
	if($ARGV[0] eq "table"){
		open STATUS, "sudo ./video 0xc1e9 15 4600 4601 0 |";
			print ; 
		close STATUS ; 
	}elsif($ARGV[0] eq "arm"){
		open STATUS, "sudo ./video 0x1ff6 60 4597 4594 4592 |";
			print ; 
		close STATUS ; 
	}else{ print "$ARGV[0] not understood - say arm or table!\n"; 

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ref: -0 tags: circular polarized antenna microstrip ultrawideband date: 02-03-2010 21:30 gmt revision:1 [0] [head]

excellent! Ultra-wideband circular polarized microstrip archimedean spiral

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ref: notes-0 tags: Gladwell talent narcissism management structure business date: 11-19-2009 06:02 gmt revision:1 [0] [head]

http://www.gladwell.com/pdf/talent.pdf -- From 2002. Old but excellent. Structure is required to achieve broad, slow to ROI projects. (It's almost common sense when expressed this way!)

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ref: work-0 tags: Ng computational leaning theory machine date: 10-25-2009 19:14 gmt revision:0 [head]

Andrew Ng's notes on learning theory

  • goes over the bias / variance tradeoff.
    • variance = when the model has a large testing error; large generalization error.
    • bias = the expected generalization error even if the model is fit to a very large training set.
  • proves that, with a sufficiently large training set, the training error will be the same as the fitting error.
    • also gives an upper bound on the generalization error in terms of fitting error in terms of the number of models available (discrete number)
    • this bound is only logarithmic in k, the number of hypotheses.
  • the training size m that a certain method or algorithm requires in order to achieve a certain level of performance is the algorithm's sample complexity.
  • shows that with infinite hypothesis space, the number of training examples needed is at most linear in the parameters of the model.
  • goes over the Vapnik-Chervonenkis dimension = the size of the largest set that is shattered by a hypothesis space. = VC(H)
    • A hypothesis space can shatter a set if it can realize any labeling (binary, i think) on the set of points in S. see his diagram.
    • In oder to prove that VC(H) is at least D, only need to show that there's at least one set of size d that H can shatter.
  • There are more notes in the containing directory - http://www.stanford.edu/class/cs229/notes/

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ref: life-0 tags: Little Pisgah mountain hiking Gerton North Carolina Florence nature preserve date: 10-21-2009 04:33 gmt revision:1 [0] [head]


awesome place! but watch out for the cows!

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ref: -0 tags: linux keyboard international characters symbols date: 10-01-2009 14:09 gmt revision:1 [0] [head]

Need to type international symbols and characters on your keyboard, e.g. for writing in another language? Do this:

 cp /usr/share/X11/locale/en_US.UTF-8/Compose ~/.XCompose 
xmodmap -e 'keycode 115 = Multi_key  Multi_key  Multi_key  Multi_key'
xmodmap -e 'keycode 116 = Multi_key  Multi_key  Multi_key  Multi_key'

Where 115 and 116 are the windows keys on my keyboard. (You can find this out for your keyboard by running 'xev');


  • <windows key> s s -> ß ("Wie heiße du?")
  • <windows><shift><~> a -> ã ("Eles estão bons")
  • <windows><shift><"> u -> ü ("Bücher")
  • <windows><,> c -> ç ("almoço")
  • <windows><=> c -> € ("Custa-la €2")


And now for something completely unrelated but highly amusing, at least in title: Optimal Brain Damage

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

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

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

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ref: work-0 tags: functional programming compilation ocaml date: 08-24-2009 14:33 gmt revision:0 [head]

The implementation of functional programming languages - book!

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ref: work-0 tags: ocaml mysql programming functional date: 07-03-2009 19:16 gmt revision:2 [1] [0] [head]

Foe my work I store a lot of analyzed data in SQL databases. In one of these, I have stored the anatomical target that the data was recorded from - namely, STN or VIM thalamus. After updating the analysis programs, I needed to copy the anatomical target data over to the new SQL tables. Where perl may have been my previous go-to language for this task, I've had enuogh of its strange quiks, hence decided to try it in Ruby (worked, but was not so elegant, as I don't actually know Ruby!) and then Ocaml.

#use "topfind"
#require "mysql"

(* this function takes a query and a function that converts entries 
in a row to Ocaml tuples *)
let read_table db query rowfunc =
	let r = Mysql.exec db query in
	let col = Mysql.column r in
	let rec loop = function
		| None      -> []
		| Some x    -> rowfunc col x :: loop (Mysql.fetch r)
	loop (Mysql.fetch r)

let _ = 
	let db = Mysql.quick_connect ~host:"crispy" ~database:"turner" ~password:"" ~user:"" () in
	let nn = Mysql.not_null in
	(* this function builds a table of files (recording sessions) from a given target, then 
	uses the mysql UPDATE command to propagate to the new SQL database. *)
	let propagate targ = 
		let t = read_table db 
			("SELECT file, COUNT(file) FROM `xcor2` WHERE target='"^targ^"' GROUP BY file")
			(fun col row -> (
				nn Mysql.str2ml (col ~key:"file" ~row), 
				nn Mysql.int2ml (col ~key:"COUNT(file)" ~row) )
		List.iter (fun (fname,_) -> 
			let query = "UPDATE `xcor3` SET `target`='"^targ^
				"' WHERE STRCMP(`file`,'"^fname^"')=0" in
			print_endline query ;
			ignore( Mysql.exec db query )
		) t ;
	propagate "STN" ; 
	propagate "VIM" ; 
	propagate "CTX" ; 
	Mysql.disconnect db ;;

Interacting with MySQL is quite easy with Ocaml - though the type system adds a certain overhead, it's not too bad.

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ref: picture-0 tags: photo arizona woman desolate fierce determined 1970 NewYorker date: 05-04-2009 20:49 gmt revision:3 [2] [1] [0] [head]

"One shot of [Lee Freidlander's], from 1969, traps an entire landscape of feeling: a boundless American sky, salted with high clouds, plus Freidlander's wife, Maria, with her slightly smiling face - inside the cab of a single truck, layering what we see through the side window with what is reflected in it. I know of long novels that tell you less "

(not the shot above, but just the same - )

some more - http://www.nga.gov.au/SurfaceBeauty/IMAGES/LRG/Fiedlander-1981.954.jpg

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ref: bookmark-0 tags: moral saints ethics personal Kant date: 05-01-2009 19:49 gmt revision:1 [0] [head]

Moral Saints by Susan Wolf

  • yes.
  • (to paraphrase:) "nothing is a good substitute for compelling personal ideals. "
  • (quote:) Perhaps what I have already said is enough to make some people begin to regard the absence of moral saints in their lives as a blessing. For there comes a point in the listing of virtues that a moral saint is likely to have that one might naturally begin to wonder whether the moral saint isn't, after all, too good - if not too good for his own good, but rather too good for hiw own well being. For the moral virtues [...] are apt to crowd out the nonmoral virtues, as well as many of the interests and personal characteristics that we generally think contribute to a healthy, well-rounded, richly developed character.
    • I agree with this, and it feels good to read this - it feels good to be justified in being another somewhat selfish, somewhat altruistic human. I imagine what she is trying to say is that extreme morality, perhaps like any extreme (and I'm cautious in apply this very broad generalization), is bad.
  • Roughly, perfectly moral people never discover anything really interesting, because discovery like this requires passion and selfishness of purpose: selfishess to pursue one's own intense interests.
  • (paraphrase) One would hope that moral figures, paragons even, would be not just moral but accomplished and attractive in nonmoral ways too. The attractiveness of most celebrities certainly does not hinge on their morality - rather it hinges on simply, how unusual, impassioned, and dominant in personality they are; yet they are not characteristically immoral.
    • Again I think this favors the mixture model..
    • On prefers the blunt, tactless, and opinionated Betsy Trotwood to the unfailingly kind and patient Agnes Copperfield.
  • (quote:) There seems to be a limit to the ammount of morality that we can stand.
  • (quote:) Morality itself does not seem to be a suitable object of passion.
    • cf. music or sports - Things which give us immense and immediate pleasure. This is what I think is necessary to sustain passion.
    • When someone gives up personal pleasures for moral obligations, one wonders not at how moral that person is, but rather how little he she loves the other things.
    • This may be because moral saints are unattractive because they make us feel uncomfortable - they expose our thoughts, vices, and flaws. Well, we don't want to give up activities that we enjoy (for more moral occupations). duh.
  • A utilitarian saint may observe that personal goals and interests are practically moral because the both enhance the happiness of the owner, as well as the happiness of those with whom the owner associates. Maximize integral given a realistic model of human behavior, yea mofos.
    • A utilitarian moral saint would then encourage others to pursue goals that are happiness-producing and attainable with a normal person's reach.
    • Ultimately this forces the argument that the utilitarian moral saint should give up sainthood (if not utilitarianism?)
    • It is to say that the hierarchy of valuations of actions, ideals, opinions, and judgments, is not exclusively hierarchal with morality at the top. Morality may be the most important, but it is not the only important criteria.
      • Morality may be the consequence of (some) humans desire to reduce things too much - to overfit the model, so to speak. It's like applying {723} to your life.
      • (quote:) The role morality plays in the development of our characters and the shape of our practical deliberations need neither be that of a universal medium through which all other values must be translated nor of an ever-present filter through which all other values must pass.
  • This is all observed from a very western viewpoint - but what about Zen Buddism? (subtext: I think is that these people are still seeking something through their studies and meditations (it is still goal directed behavior). They are frustrated by the temporal-difference structure of the reward signaling in us mammals, but abrogating it's activity does nothing to change it's homeostasis. Or maybe it does??)

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ref: Legenstein-2008.1 tags: Maass STDP reinforcement learning biofeedback Fetz synapse date: 04-09-2009 17:13 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-18846203[0] A Learning Theory for Reward-Modulated Spike-Timing-Dependent Plasticity with Application to Biofeedback

  • (from abstract) The resulting learning theory predicts that even difficult credit-assignment problems, where it is very hard to tell which synaptic weights should be modified in order to increase the global reward for the system, can be solved in a self-organizing manner through reward-modulated STDP.
    • This yields an explanation for a fundamental experimental result on biofeedback in monkeys by Fetz and Baker.
  • STDP is prevalent in the cortex ; however, it requires a second signal:
    • Dopamine seems to gate STDP in corticostriatal synapses
    • ACh does the same or similar in the cortex. -- see references 8-12
  • simple learning rule they use: d/dtW ij(t)=C ij(t)D(t) d/dt W_{ij}(t) = C_{ij}(t) D(t)
  • Their notes on the Fetz/Baker experiments: "Adjacent neurons tended to change their firing rate in the same direction, but also differential changes of directions of firing rates of pairs of neurons are reported in [17] (when these differential changes were rewarded). For example, it was shown in Figure 9 of [17] (see also Figure 1 in [19]) that pairs of neurons that were separated by no more than a few hundred microns could be independently trained to increase or decrease their firing rates."
  • Their result is actually really simple - there is no 'control' or biofeedback - there is no visual or sensory input, no real computation by the network (at least for this simulation). One neuron is simply reinforced, hence it's firing rate increases.
    • Fetz & later Schimdt's work involved feedback and precise control of firing rate; this does not.
    • This also does not address the problem that their rule may allow other synapses to forget during reinforcement.
  • They do show that exact spike times can be rewarded, which is kinda interesting ... kinda.
  • Tried a pattern classification task where all of the information was in the relative spike timings.
    • Had to run the pattern through the network 1000 times. That's a bit unrealistic (?).
      • The problem with all these algorithms is that they require so many presentations for gradient descent (or similar) to work, whereas biological systems can and do learn after one or a few presentations.
  • Next tried to train neurons to classify spoken input
    • Audio stimului was processed through a cochlear model
    • Maass previously has been able to train a network to perform speaker-independent classification.
    • Neuron model does, roughly, seem to discriminate between "one" and "two"... after 2000 trials (each with a presentation of 10 of the same digit utterance). I'm still not all that impressed. Feels like gradient descent / linear regression as per the original LSM.
  • A great many derivations in the Methods section... too much to follow.
  • Should read refs:
    • PMID-16907616[1] Gradient learning in spiking neural networks by dynamic perturbation of conductances.
    • PMID-17220510[2] Solving the distal reward problem through linkage of STDP and dopamine signaling.


[0] Legenstein R, Pecevski D, Maass W, A learning theory for reward-modulated spike-timing-dependent plasticity with application to biofeedback.PLoS Comput Biol 4:10, e1000180 (2008 Oct)
[1] Fiete IR, Seung HS, Gradient learning in spiking neural networks by dynamic perturbation of conductances.Phys Rev Lett 97:4, 048104 (2006 Jul 28)
[2] Izhikevich EM, Solving the distal reward problem through linkage of STDP and dopamine signaling.Cereb Cortex 17:10, 2443-52 (2007 Oct)

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ref: Oskoei-2008.08 tags: EMG pattern analysis classification neural network date: 04-07-2009 21:10 gmt revision:2 [1] [0] [head]

  • EMG pattern analysis and classification by Neural Network
    • 1989!
    • short, simple paper. showed that 20 patterns can accurately be decoded with a backprop-trained neural network.
  • PMID-18632358 Support vector machine-based classification scheme for myoelectric control applied to upper limb.
    • myoelectric discrimination with SVM running on features in both the time and frequency domain.
    • a survace MES (myoelectric sensor) is formed via the superposition of individual action potentials generated by irregular discharges of active motor units in a muscle fiber. It's amplitude, variance, energy, and frequency vary depending on contration level.
    • Time domain features:
      • Mean absolute value (MAV)
      • root mean square (RMS)
      • waveform length (WL)
      • variance
      • zero crossings (ZC)
      • slope sign changes (SSC)
      • William amplitude.
    • Frequency domain features:
      • power spectrum
      • autoregressive coefficients order 2 and 6
      • mean signal frequency
      • median signal frequency
      • good performance with just RMS + AR2 for 50 or 100ms segments. Used a SVM with a RBF kernel.
      • looks like you can just get away with time-domain metrics!!

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ref: Huber-2004.07 tags: sleep REM SWS wilson synaptic strength date: 04-01-2009 17:50 gmt revision:2 [1] [0] [head]

http://www.the-scientist.com/2009/04/1/34/1/ -- good layperson-level review of the present research on sleep. Includes interviews with Strickgold and other prominents. References:

http://www.the-scientist.com/2009/04/1/15/1/ -- points out that Western sleep style is a relative outlier compared to sleeping in other cultures. More 'primitive' cultures have polyphasic sleep, with different stages of alertness, dozing, napping, disengaged, vigilance, etc.

  • Quote: Other cultures tend towards "multiple and multiage sleeping partners; frequent proximity of animals; embeddedness of sleep in ongoing social interaction; fluid bedtimes and wake times; use of nighttime for ritual, sociality, and information exchange; and relatively exposed sleeping locations that require fire maintenance and sustained vigilance."


[0] Huber R, Ghilardi MF, Massimini M, Tononi G, Local sleep and learning.Nature 430:6995, 78-81 (2004 Jul 1)
[1] Klintsova AY, Greenough WT, Synaptic plasticity in cortical systems.Curr Opin Neurobiol 9:2, 203-8 (1999 Apr)
[2] Vyazovskiy VV, Cirelli C, Pfister-Genskow M, Faraguna U, Tononi G, Molecular and electrophysiological evidence for net synaptic potentiation in wake and depression in sleep.Nat Neurosci 11:2, 200-8 (2008 Feb)
[3] Pavlides C, Winson J, Influences of hippocampal place cell firing in the awake state on the activity of these cells during subsequent sleep episodes.J Neurosci 9:8, 2907-18 (1989 Aug)
[4] Pompeiano M, Cirelli C, Arrighi P, Tononi G, c-Fos expression during wakefulness and sleep.Neurophysiol Clin 25:6, 329-41 (1995)
[5] Hill S, Tononi G, Modeling sleep and wakefulness in the thalamocortical system.J Neurophysiol 93:3, 1671-98 (2005 Mar)
[6] Aton SJ, Seibt J, Dumoulin M, Jha SK, Steinmetz N, Coleman T, Naidoo N, Frank MG, Mechanisms of sleep-dependent consolidation of cortical plasticity.Neuron 61:3, 454-66 (2009 Feb 12)

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ref: Tononi-2006.02 tags: sleep synaptic homeostasis plasticity date: 03-20-2009 15:45 gmt revision:1 [0] [head]

PMID-16376591[0] Sleep function and synaptic homeostasis.

  • Sleep keeps the neural network stable & the synaptic weights in check.
    • if you don't sleep do you get epilepsy?? don't have access to the article, would have to read it.


[0] Tononi G, Cirelli C, Sleep function and synaptic homeostasis.Sleep Med Rev 10:1, 49-62 (2006 Feb)

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ref: Nishida-2007.04 tags: sleep spindle learning nap NREM date: 03-06-2009 17:56 gmt revision:1 [0] [head]

PMID-17406665[0] Daytime naps, motor memory consolidation and regionally specific sleep spindles.

  • asked subjects to learn a motor task with their non-dominant hand, and then tested them 8 hours later.
  • subjects that were allowed a 60-90 minute siesta improved their performance significantly relative to controls and relative to previous performance.
  • when they subtracted EEG activity of the non-learning hemisphere from the learning hemisphere, spindle activity was strongly correlated with offline memory improvement.


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ref: HilArio-2007.01 tags: Rui Costa endocannabinoid habit reward striatum basal ganglia date: 03-05-2009 19:04 gmt revision:0 [head]

PMID-18958234 Endocannabinoid Signaling is Critical for Habit Formation.

  • quick review (the intro is packed with grat information):
    • in goal-directed learning, behavior is highly sensitive to the incentive value of the outcome, and contingency between the action and the outcome.
    • with repetition actions become both more efficient and more automatic.
    • after extensive training, rats move from goal-directed behavior to more habitual response independent of outcome value.
      • random interval schedules favor this more than random ratio reward schedules.
        • in mice, random interval schedules promoted habit formation, whereas random ratio schedules promoted acquisition of goal-directed behaviors. does this also apply to humans? I would guess so. Might be an interesting tool to have in the toolbox.
        • interval schedules promoted the exploration of a random lever whereas ratio schedules promoted the exploitation of the reward lever.
    • the underlying circuitry supporting goal-directed behav and habit formation are different:
      • goal directed behavior seems to require the associative BG/cortex including:
        • dorsomedial or associative striatum (medial!)
          • COMT, a transporter, is more highly expressed here than DAT.
        • pre-limbic ctx
        • mediodorsal thalamus
      • habit formation requries:
        • dorsolateral or sensorimotor striatum (lateral!)
          • DAT, dopamine transporter, is highly expressed here.
        • infralimbic cortex
    • amphetamine sensitization can lead to increased spine density in medium spiny neurons in the dorsolateral striatum, while decreasing spine density in the dorsomedial striatum. (interesting!)
    • lesions of nigrostriatal input to dorsolateral striatum impairs habit formation;
    • infusion of dopamine into the ventral medial prefrontal cortex favors goal-directed behavior
      • that is a rather broad statement to make ...
  • endocannabinoid release in the striatum is required for LTD induction.
  • endocannabinoid signaling regulated bt DA.
  • CB1 (the receptor implicated in addiction) is highly expressed in the dorsolateral striatum (habit!) at both excitatory and inhibitory terminals.
  • used mice with CB1 mutations therefore!
  • CB1 mutant mice have impaired habit formation and enhanced exploration.
    • suggest that endocannabinoid signaling is critical for both habit formation and increased exploration in interval schedules.

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ref: -0 tags: computational geometry triangulation ocaml kicadocaml zone fill edge date: 01-26-2009 01:47 gmt revision:3 [2] [1] [0] [head]

I have been working hard to add zone support to kicadocaml since the implementation in kicad's PCBnew is somewhat borken (at least for my boards). It is not a very easy task!

Roughly, the task is this: given a zone of copper pour, perhaps attached to the ground net, and a series of tracks, vias, and pads also on that layer of the PCB but not on the same net, form cutouts in the zone so that there is an even spacing between the tracks/vias and zone.

Currently I'm attacking the problem using triangles (not polygons like the other PCB softwares). I chose triangles since I'm using OpenGL to display the PCB, and triangles are a very native mode of drawing in OpenGL. Points are added to the triangle mesh with an incremental algorithm, where the triangles are stored as a linked-mesh : each triangle has a pointer (index#) to the triangle off edge ab,bc,ca. This allows finding the containing triangle when inserting a point a matter of jumping between triangles; since many of the points to be inserted are close to eachother, this is a relatively efficient algorithm. Once the triangle containing a point to be inserted is found, the triangle is split into three, the pointers are updated appropriately, and each triangle is tested to see if flipping with it's pair would result in a net larger smallest interior angle between the two. (This is not the same as Delaunay's criteria, but it is simpler, and it produces equally beautiful pictures.)

The problem is when two triangles are allowed to overlap or a gap is allowed - this makes the search algorithm die or get into a loop, and is a major major problem of the approach. In Guibas and Stolfi's paper, "Primitives for the manipulation of general subdivisions and the computation of Voronoi diagrams", they use an edge data structure, rather than a triangle data structure, which I suppose avoids this problem. I was lazy when starting this project, and chose the more obvious triangle-centric way of storing the data.

The insertion of points is actually not so hard; the big problem is making sure the edges in the original list of polygons are represented in the list of edges in the triangle mesh. Otherwise, triangles will span edges, which will result in DRC violations (e.g.g copper too close to vias). My inefficient way of doing this is to calculate, for all triangles, their intersections with the polygon segments, then adding this to the mesh until all segments are represented in the list. This process, too, is prone to numerical instability.

Perhaps the solution is to move back to an edge-centric data representation, so that certain edges can be 'pinned' or frozen, and hence they are guaranteed to be in the triangle mesh's edge list. I don't know; need to think about this more.

Update: I got most of it working; at least the triangulation & making sure the edges are in the triangle mesh are working. Mostly there were issues with numerical precision with narrow / small triangles; I rewrote the inside triangle function to use the cross product, which helped (this seems like the simplest way, and it avoids divisions!):

let insidetri a b c d = 
	cross (sub b a) (sub d a) > 0.0 &&
	cross (sub c b) (sub d b) > 0.0 &&
	cross (sub a c) (sub d c) > 0.0 

as well as the segment-segment intersection algorithm:

let intersect a b c d = 
	(* see if two line segments intersect *)
	(* return the point of intersection too *)
	let ab = sub b a in
	(* a prime is the origin *)
	let bp = length ab in
	let xx = norm ab in
	let yy = (-1.) *. (snd xx) , (fst xx) in
	let project e = 
		(dot (sub e a) xx) , (dot (sub e a) yy)
	let cp = project c in
	let dp = project d in
	let cd = sub dp cp in
	let m = (fst cd) /. (snd cd) in
	let o = (fst cp) -. m *. (snd cp) in
	let e = add (scl ab (o /. bp)) a in
	(* cp and dp must span the x-axis *)
	if ((snd cp) <= 0. && (snd dp) >= 0.) || ((snd cp) >= 0. && (snd dp) <= 0.) then (
		if o >= 0. && o <= bp then ( true, e )
		else ( false, e )
	) else ( false, e )

Everything was very sensitive to ">" vs. ">=" -- all must be correct. All triangles must be CCW, too, for the inside algorithm to work - this requires that points to be inserted close to a triangle edge must be snapped to that edge to avoid any possible CW triangles. (Determining if a triangle is CW or CCW is as simple as measuring the sign of the smallest cross product between two segments). I tried, for a day or so, to include a specialized function to insert points along a triangle's edge, but that turned out not to matter; the normal flipping routine works fine. I also tried inserting auxiliary points to try to break up very small triangles, but that really didn't affect the stability of the algorithm much. It is either correct, or it is not, and my large board was a good test suite. I have, however, seeded the triangularization with a grid of (up to) 20x20 points (this depends on the aspect ratio of the region to be filled - the points are equally spaced in x and y). This adds (max) 800 triangles, but it makes the algorithm more stable - fewer very narrow triangles - and we are working with sets of 10,000 triangles anyway for the large zones of copper.

Some corrections remain to be done regarding removing triangles based on DRC violation and using the linked-mesh of triangles when calculating edge-triangle edge intersection, but that should be relatively minor. Now I have to figure out how to store it in Kicad's ".brd" file format. Kicad uses "Kbool" library for intersection polygons - much faster than my triangle methods (well, it's in C not ocaml) - and generates concave polygons not triangles. Would prefer to do this so that I don't have to re-implement gerber export. (Of course, look at how much I have re-implemented! This was originally a project just to learn ocaml - Well, gotta have some fun :-)

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ref: RAzsa-2008.01 tags: nAChR nicotinic acetylchoine receptor interneurons backpropagating LTP hippocampus date: 10-08-2008 17:37 gmt revision:0 [head]

PMID-18215234[0] Dendritic nicotinic receptors modulate backpropagating action potentials and long-term plasticity of interneurons.

  • idea: nAChRs are highly permeable to Ca+2, LTP is dependent on Ca2+, so they tested nAChR -> LTP in interneurons of rat hippocampus using whole-cell electrophysiology and 2-photon imaging.
  • Here we show that precisely timed activation of dendritic α7-nAChRs boosts the induction of LTP by excitatory postsynaptic potentials (EPSPs) and synaptically triggered dendritic Ca2+ transients.
  • suggest that this rapid (ionotropic) method of memory encoding and retrieval via LTP/D facilitated by acetylcholine.
  • I haven't read much of the article, since it is much out of my field of experience.


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ref: Gage-2005.06 tags: naive coadaptive control Kalman filter Kipke date: 10-03-2008 16:34 gmt revision:1 [0] [head]

PMID-15928412[0] Naive coadaptive Control May 2005. see notes


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ref: -0 tags: differential dynamic programming machine learning date: 09-24-2008 23:39 gmt revision:2 [1] [0] [head]

excellent bibliography.

  • Jacobson, D. and Mayne, D., Differential Dynamic Programming, Elsevier, New York, 1970. in Perkins library.
  • Bertsekas, Dimitri P. Dynamic programming and optimal control Ford Library.
  • Receding horizon differential dynamic programming
    • good for high-dimensional problems. for this paper, they demonstrate control of a swimming robot.
    • webpage, including a animated gif of the swimmer
    • above is a quote from the conclusions -- very interesting!

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ref: notes-0 tags: ocaml run external command stdin date: 09-10-2008 19:32 gmt revision:1 [0] [head]

It is not obvious how to run an external command in ocaml & get it's output from stdin. Here is my hack, which simply polls the output of the program until there is nothing left to read. Not very highly tested, but I wanted to share, as I don't think there is an example of the same on pleac

let run_command cmd = 
	let inch = Unix.open_process_in cmd in
	let infd = Unix.descr_of_in_channel inch in
	let buf = String.create 20000 in
	let il = ref 1 in
	let offset = ref 0 in
	while !il > 0 do (
		let inlen = Unix.read infd buf !offset (20000- !offset) in
		il := inlen ; 
		offset := !offset + inlen;
	) done; 
	ignore(Unix.close_process_in inch);  
	if !offset = 0 then "" else String.sub buf 0 !offset

Note: Fixed a nasty string-termination/memory-reuse bug Sept 10 2008

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ref: notes-0 tags: linear discriminant analysis LDA EMG date: 07-30-2008 20:56 gmt revision:2 [1] [0] [head]

images/588_1.pdf -- Good lecture on LDA. Below, simple LDA implementation in matlab based on the same:

% data matrix in this case is 36 x 16, 
% with 4 examples of each of 9 classes along the rows, 
% and the axes of the measurement (here the AR coef) 
% along the columns. 
Sw = zeros(16, 16); % within-class scatter covariance matrix. 
means = zeros(9,16); 
for k = 0:8
	m = data(1+k*4:4+k*4, :); % change for different counts / class
	Sw = Sw + cov( m ); % sum the 
	means(k+1, :) = mean( m ); %means of the individual classes
% compute the class-independent transform, 
% e.g. one transform applied to all points
% to project them into one plane. 
Sw = Sw ./ 9; % 9 classes
criterion = inv(Sw) * cov(means); 
[eigvec2, eigval2] = eig(criterion);

See {587} for results on EMG data.

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


dishdnanameconc ug/ululug

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ref: bookmark-0 tags: Ocaml python paradox programming finance date: 03-10-2008 21:29 gmt revision:2 [1] [0] [head]

  • this trading firm used OCaml, apparently to exclusion: http://www.janestcapital.com/yaron_minsky-cufp_2006.pdf
  • they also reference the python paradox. interesting, I'll have to check into Ocaml.
  • or, rather, Lisp. this article is quite convincing!
    • quote: If you're trying to solve a hard problem with a language that's too low-level, you reach a point where there is just too much to keep in your head at once.
    • quote: Any sufficiently complicated C or Fortran program contains an ad hoc informally-specified bug-ridden slow implementation of half of Common Lisp.
      • well, yes, this happened a bit in BMI with variables that were indexed by name :(
  • also see this excellent, extensive article.

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ref: business-0 tags: North Carolina Business guide taxes date: 01-06-2008 17:39 gmt revision:2 [1] [0] [head]

http://www.nccommerce.com/NR/rdonlyres/CC5488D0-9B3E-4C32-BEF4-4B88630CE3F1/0/BusinessNotes.pdf ; linked from NC department of commerce business center

  • business owners are responsible for listing personal property with the county's assessor office in the county where the business is located.
  • must file income and franchise tax (obviously)
  • Security offers and sales in NC are subject to NC Securities act -- 919-733-3924, http://www.sosnc.com/

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ref: notes-0 tags: patent maintenance fee date: 01-06-2008 17:23 gmt revision:0 [head]


  • A maintenance fee is due 3 1/2, 7 1/2 and 11 1/2 years after the original grant for all patents issuing from the applications filed on and after December 12, 1980

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ref: notes-0 tags: Blackfin perl loopcounters registers ABI application-binary interface gcc assembly date: 10-19-2007 17:24 gmt revision:2 [1] [0] [head]

The problem: I have an interrupt status routine (ISR) which can interrupt the main, radio-servicing routine at any time. To keep the ISR from corrupting the register values of the main routine while it works, these registers must be pushed, and later popped, to the stack. Now, doing this takes time, so I'd prefer to pop / push as few registers as possible. Namely, I don't want to push/pop the hardware loop registers - LC0 (loop counter 0), LB0 (loop bottom 0, where the hardware loop starts) & LT0 (loop top 0, where the hardware loop ends).

Gcc seems to only touch bank 1, never bank 0, so I don't have to save the 3 regs above. However, to make sure, I've written a perl file to examine the assembled code:

my $file = "decompile.asm"; 
open(FH, $file); 
@j = <FH>; 
my $i=0; 
my @badregs = ("LC0", "LB0", "LT0"); 
foreach $reg (@badregs){
	foreach $k (@j){
		if($k =~ /$reg/){
			print "touch register $reg : $k";
#tell make if we found problems or not.
	exit 1;
	exit 0;

'make' looks at the return value perl outputs, as instructed via the makefile (relevant portion below):

	rm -f *.ldr
	$(LDR) -T BF532 -c headstage.ldr $<
	bfin-elf-objdump -d headstage.dxe > decompile.asm
	perl register_check.pl

if it finds assembly which accesses the 'bad' registers, make fails.

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ref: bookmark-0 tags: phase converter gilbert cell analog multiplication RF bipolar transistors phase detector modulator date: 07-23-2007 20:48 gmt revision:0 [head]


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ref: life-0 tags: life diary portugal ana date: 07-08-2007 22:43 gmt revision:4 [3] [2] [1] [0] [head]

  • Thursday 28 June sat on runway for 5 hours, made it to NY but missed the connection to Lisbon so therefore had to wait in Newark for a Day. Slept in the meditation room and soiled the islamic rug.
  • Friday 29 June Called mom in the morning and went to NY, ate and slept, then went for a quick walk with the family & tux around little dam lake, ana liked the area alot, said it was super beautiful. Dad read my grant and said that i need to more clearly define Miguel's rights as a client/purchaser. Went back to newark, found the black ipod, got on the standby flight to lisbon, sat next to a really angsty portuguese.
  • Saturday 30 June Tired, picked up at airport by ana's parents, slept uncomfortably on the highway from Lisbon to Coimbra (ana's father drives very quickly). took a nap. went into Coimbra to go shopping at the big mall and later went to a oliveira family party where I spoke with Pedro (the elder).. too much portuguese, did not interact very much. Later went to Coimbra's republican square, to meet some of ana's friends, but i didn't have a great time - was too exhausted!
  • Sunday 1 July Went with the oliveira family to lunch in Figuiera de Foz, saw the ultralights, walked on the beach after a very long lunch & otherwise saw the town (pretty nice beachisde resort, Antonio went there frequently as a kid). Then went up to the Serra Boa Viagem, where it was damp, then to Praia de Mira where we rented paddle boats, walked along the boardwalk, and ate dinner after a long trip through the coastal wilderness. Went back and slept, slept, slept.
  • Monday 2 July - woke up late and went shopping for the stuff for our trip to the mountains (tent, sleeping mat, food). Left rather late, and traveled past Porto to Esposende where we had a long walk along the beach, coffee at the Bar de Praia. This eventually left us out of time, so we went to the orbitur camp site nearby, checked in late, then ate octopus black beans and flan at a nice local restaurant.. went to bed late, slept well.
  • Tuesday 3 July - Woke up late arg to a gray and rainy day. Discovered that we had put up the tent incorrectly late that night. spent a long time seaking out internet back in Esposende because ana wanted to meet up with her friends & tell them about the party she was planning for Friday. Eventually we were on our way to this area near the boarder of Portugal and Spain -- but then we ran out of gas! tried pushing the car up the slope, but it was too hard, too heavy, and ana called the road-rescue-crew then later we went into a absolutely beautiful farmhouse to locate some diesel. The people inside were rather affable, and gave us 5 liters of petrol, which was enough to get us to the next gas pump or 'bomba'. I managed to spill diesel on my shorts - not good because I only had two! Later we went to the beautiful village of Ponte Da Barca (I think) where we walked along the river , visited the public pool (absolutely gorgeous!), walked through the city, and eventually got hungry and started looking for somewhere to eat. We found a very nice place - Kibom i think - and i had steak and mushrooms. Left after yet another desultory meal, and went to the Dois Rios campismo, where we set up the tent (correctly, this time) and got some rest!
  • Wednesday 4 July - Awoke to a bright and clear day in the mountains; the campismo was much more interesting and nice during the day. Ate cereal and iogurte for breakfast, then traveled to Lindoso. Along the way we stopped to try a trail, but it turned out to be very overgrown and ana was afraid of vipers, so we did not go very far. In lindoso we visited a small ancient castle where ana's parents called to say that they were coming (this annoyed ana a bit), then went across the river up the hills , where we climbed pig hill and saw cows , horses, and feral dogs . it was really super incredible up there - wild, like scotland. I love that type of place. It was a clear day, too, so you could see at least 50km. we took the road further past many small vilages, winding through the hills, and saw many locals. Stopped for lunch by Lamas de Mouro, then continued to the small road by Castro Laboreiro, where we hiked for some 5 hours in the dazzling sunlight along the high plains of that region. It was truly incredible! I'll have to add photos: , , , , On the way there we had to go around a bunch of bulls and later we passed by a set of horses.. still later we crossed into Spain, as indicated by the Spanish no-trespassing sign (without needing to worry about border guards!). At the turnaround point we found a geyser of water .. in the middle of nowhere .. and ana called her parents to find out where they were. They had traveled all day & got stuck in the traffic around Porto, and eventually met us at the end of the trail in the high mountain pass. Ana and I then followed her parents through spain to a small restaurant in Campo do Geres (??), whence the subsequently left for Coimbra (Antonio had the day off - it was Coimbra day. Eventually got back to porto, found a campismo by Matosinhos. Got in too late to check in officially, so asked to pay later.
  • Thursday 5 July - Awoke early, too early, to take a bus to Porto to take the train to the boat trip down the river. Spent the little extra time in porto drinking cafe (of course!) and going to the river. Slept most of the trainride; ana slept almost all! The boatride was rather chill ; I liked the forest and ana liked the vineyards; we both liked to the small beaches along the way, some of which had people, especially as the day wore on. Stopped in Gaia to ride a small pedal kart (kinda the highlight of the day), and eat some spicy thai food (thank god - portuguese do not believe much in spices!). Then it was late, and we had to wait for the bus back to Matozinhos (10pm); eventually got back, but again too late to pay, but fortunately ana called ahead and the conta was filled out already. Drove back to Coimbra, once again at very high velocity ;)
  • Friday 6 July - woke up really late, like 1pm, and went shopping for the party, then later played in the pool and read calmly by the poolside, the waters of which had warmed up appreciably. Met Rita and Luisa (i think), who we met with Justin in NYC, then later Paulo and Vitor & their namoradas for dinner. This lasted until 3 in the morning, mostly because Paulos gf wouldn't shutup.
  • Saturday 7 July - Ana visited her grandfather whilest I fitzed with the computer; later Denisa and another Rita came over for lunch, after which we went into Coimbra. returned home @ 6, then went out again to see the graduation ceremony for 3 students in Pharmacy, after which we spent some time shopping and walking around the area near the university in Coimbra. Ate dinner and were too tired for further escapades in the city.

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ref: notes-0 tags: recording tech tbsi biosignal telemetry date: 05-20-2007 16:40 gmt revision:1 [0] [head]

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

Anatomy of the spinal cord

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


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ref: life-0 tags: Japan photos pictures Nathan Misha Kyoto date: 04-21-2007 20:41 gmt revision:1 [0] [head]

Nathan, Misha, and their lives went to Japan for a week to work with the roboticists @ ATR. During the off time, they spent time exploring and photographing Japan. Misha lent me his camera to video record Clementine, and in the process of trying to free up space in the camera's memory, I found these excellent pictures taken by (presumably) Misha. There were other very nice pictures, but they contain Misha, Nathan etc so I excluded them.

the photo below is by far the best.

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ref: Kawato-1999.12 tags: kawato inverse dynamics cerebellum motor control learning date: 04-09-2007 22:45 gmt revision:1 [0] [head]

PMID-10607637[0] Internal models for motor control and trajectory planning

  • in this review, I will discuss evidence supporting the existence of internal models.
  • fast coordinated arm movement canot be executed under feedback control, as biological feedback loops are slow and have low gains. hence, the brain mostly needs to control things in a pure feedforward manner.
    • visual feedback delay is about 150-200ms.
    • fast spinal reflexes still require 30-50ms; large compared to fast movements (150ms).
    • muscle intrinsic mechanical properties produce proportional (stiffness) and derivative (viscosity) gains without delay.
    • inverse models are required for fast robotics, too. http://www.erato.atr.co.jp/DB/
  • talk about switching external force field to gauge the nature of the internal model - these types of experiments verily prove that feedforward / model-based control is happening. has anyone shown what happens neuronally during the course of this learning? I guess it might be in my datar.


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ref: Scott-2004.07 tags: Scott motor control optimal feedback cortex reaching dynamics review date: 04-09-2007 22:40 gmt revision:1 [0] [head]

PMID-15208695[0] PDF HTML summary Optimal feedback control and the neural basis of volitional motor control by Stephen S. Scott


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ref: Chan-2006.12 tags: computational model primate arm musculoskeletal motor_control Moran date: 04-09-2007 22:35 gmt revision:1 [0] [head]

PMID-17124337[0] Computational Model of a Primate Arm: from hand position to joint angles, joint torques, and muscle forces ideas:

  • no study so far has been able to incorporate all of these variables (global hand position & velocity, joint angles, joint angular velocities, joint torques, muscle activations)
  • they have a 3D, 7DOF model that translate actual motion to optimized muscle activations.
  • knock the old center-out research (nice!)
  • 38 musculoskeletal-tendon units
  • past research: people have found correlations to both forces and higher-level parameters, like position and velocity. these must be transformed via inverse dynamics to generate a motor plan / actually move the arm.
  • used SIMM to optimize the joint locations to replicate actual movements...
  • assume that the torso is the inertial frame.
  • used infrared Optotrak 3020
  • their model is consistent - they can use the inverse model to calculate muscle activations, which when fed back into the forward model, results in realistic movements. still yet, they do not compare to actual EMG.
  • for working with the dynamic model of the arm, they used AUTOLEV
    • I wish i could figure out what the Kane method was, they seem to leverage it here.
  • their inverse model is pretty clever:
  1. take the present attitude/orientation & velocity of the arm, and using parts of the forward model, calculate the contributions from gravity & coriolis forces.
  2. subtract this from the torques estimated via M*A (moment of interia times angular acceleration) to yield the contributions of the muscles.
  3. perturb each of the joints / DOF & measure the resulting arm motion, integrated over the same period as measurement
  4. form a linear equation with the linearized torque-responses on the left, and the muscle torque contributions on the right. Invert this equation to get the actual joint torques. (presumably the matrix spans row space).
  5. to figure out the muscle contributions, do the same thing - apply activation, scaled by the PCSA, to each muscle & measure the resulting torque (this is effectively the moment arm).
  6. take the resulting 38x7 matrix & p-inverse, with the constraint that none of the muscle activations are negative, yielding a somewhat well-specified muscle activation. not all that complicated of a method


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ref: Humphrey-1970.11 tags: BMI original Humphrey date: 04-09-2007 19:47 gmt revision:1 [0] [head]

PMID-4991377[0] Predicting measures of motor performance from multiple cortical spike trains.

Recordings have been obtained simultaneously from several, individually selected neurons in the motor cortex of unanesthetized monkey as the animal performed simple arm movements. With the use of comparatively simple quantitative procedures, the activity of small sets of cells was found to be adequate for rather accurate real-time prediction of the time course of various response measurements. In addition, the results suggest that hypotheses concerning the response variables "controlled" by cortical motor systems may well depend upon whether or not the temporal relations between simultaneously active neurons are taken into account.

cited in miguel's book, "Methods for Neural ensemble recordings". However, I can't get the text online.


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ref: DeLong-1974.05 tags: motor control basal ganglia cerebellum motor cortex DeLong putamen original date: 04-09-2007 01:51 gmt revision:1 [0] [head]

PMID-4219745[0] Relation of basal ganglia, cerebellum, and motor cortex units to ramp and ballistic limb movements.

  • monkey trained to make both ballistic movement and slow, pulling movements by pulling a manipulandum between three targets.
  • cells in the putamen discharged preferentially during slow movements.
    • consistent with a sequence / temporal scaling (?) role.
    • also consistent with the cerebellum creating rapid/feedforward trajectories.
  • cells in the motor cortex discharged for both types of movements, though a bit more for ballisic type movements (where the forces were higher).
  • paper is thankfully short and concise.
    • and also humble: "the mere correlation of unit discharge with some aspect of a movement without knowledge of the peripheral site influenced by the unit under study can only provide grounds for speculation".


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

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

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

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

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


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ref: Sanchez-2004.01 tags: BMI nicolelis florida Carmena Principe date: 04-06-2007 21:02 gmt revision:3 [2] [1] [0] [head]

PMID-17271543[] http://hardm.ath.cx:88/pdf/sanchez2004.pdf


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

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

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


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ref: Cabel-2001.1 tags: Stephen Scott Kinarm motor control date: 04-04-2007 21:51 gmt revision:0 [head]

PMID-11600665[] Neural Activity in Primary Motor Cortex Related to Mechanical Loads Applied to the Shoulder and Elbow During a Postural Task

  • experiment w/ the kinarm. w/ Stephen Scott.
  • roughly equal numbers of neuons responsive to mechanical loads on shoulder, elbow, and both.
  • neural activity is also strongly influenced by the specific motor patterns used to perform a given task.


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ref: life-0 tags: spooky house ana adventure grave date: 03-19-2007 01:11 gmt revision:0 [head]


go there!! be frightened!!

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

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

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


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ref: SidibAc)-1997.06 tags: GPi anatomy retrograde tracing VL ventrolateral CM centromedian thalamus GPe striatum date: 03-11-2007 06:08 gmt revision:0 [head]

PMID-9183697 Efferent connections of the internal globus pallidus in the squirrel monkey: I. Topography and synaptic organization of the pallidothalamic projection.

  • ventrolateral (e.g. toward the bottom & side :) GPi projects to the postcommisural putamen & the VL thalamus & central CM.
  • dorsal GPi projects to the caudate and ventral striatum ("limbic striatum")
  • both areas also project to nuclei in the thalamus:
    • parvocellular ventral anterior nucleus (VApc)
    • dorsal VL
    • caudal CM/PF
  • the parafasicular nucleus (PF) was a site of a large number of associative/limbic projections.

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ref: Kita-1999.05 tags: globus pallidus GPe caudate putamen anatomy projection date: 03-11-2007 04:09 gmt revision:0 [head]

PMID-10380964 Monkey globus pallidus external segment neurons projecting to the neostriatum.

  • horseradish-peroxidase study in rhesus monkeys.
  • 30% of GPe neurons project to the neostriatum (caudate and putamen)

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ref: notes-0 tags: SNR MSE error multidimensional mutual information date: 03-08-2007 22:33 gmt revision:2 [1] [0] [head]

http://ieeexplore.ieee.org/iel5/516/3389/00116771.pdf or http://hardm.ath.cx:88/pdf/MultidimensionalSNR.pdf

  • the signal-to-noise ratio between two vectors is the ratio of the determinants of the correlation matrices. Just see equation 14.

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

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

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ref: Brown-2001.11 tags: Huntingtons motor_learning intentional implicit cognitive deficits date: 0-0-2007 0:0 revision:0 [head]

PMID-11673321 http://brain.oxfordjournals.org/cgi/content/full/124/11/2188 :

  • 16 genetically-confirmed Huntington's patients (and matched controls) trained on a task using trial and error learning (intentional), and implicit learning (unintentional).
  • the task setup was simple: they had to press one of four keys arranged in a cross (with center) either in response to commands or while guessing a sequence of a few keys.
  • Within the random, commanded task there was a sequence that could/should be noticed.
  • Huntington's patients performed worse on the intentional learning segment, but comparably on the implicit learning / implicit sequence awareness, though the latter test seems rather weak to me.

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ref: bookmark-0 tags: robot kinematics lagrangian dynamics date: 0-0-2007 0:0 revision:0 [head]


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ref: notes-0 tags: SQL kinarm count date: 0-0-2007 0:0 revision:0 [head]

SELECT file, COUNT(file) FROM info2 WHERE unit>1 AND maxinfo/infoshuf > 10 AND analog < 5 GROUP BY file ORDER BY COUNT(file) DESC

to count the number of files matching the criteria.. and get aggregate frequentist statistics.

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ref: bookmark-0 tags: thalamus basal ganglia neuroanatomy centromedian red nucleus images date: 0-0-2007 0:0 revision:0 [head]

http://www.neuroanatomy.wisc.edu/coro97/contents.htm --coronal sections through the thalamus, very nice!

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

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

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ref: Flash-2001.12 tags: Flash Sejnowski 2001 computational motor control learning PRR date: 0-0-2007 0:0 revision:0 [head]

PMID-11741014 Computational approaches to motor control. Tamar Flash and Terry Sejnowski.

  • PRR = parietal reach region
  • essential controviersies (to them):
    • the question of motor variables that are coded by neural populations.
    • equilibrium point control vs. inverse dynamics (the latter is obviously better/more correct)

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ref: bookmark-0 tags: plexon documenation data file structure reading plx date: 0-0-2006 0:0 revision:0 [head]


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ref: bookmark-0 tags: job_search professional employment wisdom date: 0-0-2006 0:0 revision:0 [head]


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ref: bookmark-0 tags: Bayes Baysian_networks probability probabalistic_networks Kalman ICA PCA HMM Dynamic_programming inference learning date: 0-0-2006 0:0 revision:0 [head]

http://www.cs.ubc.ca/~murphyk/Bayes/bnintro.html very, very good! many references, well explained too.

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ref: bookmark-0 tags: muscle artifial catalyst nanotubes shape-memory alloy date: 0-0-2006 0:0 revision:0 [head]


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ref: notes bookmarks-0 tags: spike sorting bayes spectral_analysis date: 0-0-2006 0:0 revision:0 [head]

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ref: abstract-0 tags: tlh24 error signals in the cortex and basal ganglia reinforcement_learning gradient_descent motor_learning date: 0-0-2006 0:0 revision:0 [head]

Title: Error signals in the cortex and basal ganglia.

Abstract: Numerous studies have found correlations between measures of neural activity, from single unit recordings to aggregate measures such as EEG, to motor behavior. Two general themes have emerged from this research: neurons are generally broadly tuned and are often arrayed in spatial maps. It is hypothesized that these are two features of a larger hierarchal structure of spatial and temporal transforms that allow mappings to procure complex behaviors from abstract goals, or similarly, complex sensory information to produce simple percepts. Much theoretical work has proved the suitability of this organization to both generate behavior and extract relevant information from the world. It is generally agreed that most transforms enacted by the cortex and basal ganglia are learned rather than genetically encoded. Therefore, it is the characterization of the learning process that describes the computational nature of the brain; the descriptions of the basis functions themselves are more descriptive of the brain’s environment. Here we hypothesize that learning in the mammalian brain is a stochastic maximization of reward and transform predictability, and a minimization of transform complexity and latency. It is probable that the optimizations employed in learning include both components of gradient descent and competitive elimination, which are two large classes of algorithms explored extensively in the field of machine learning. The former method requires the existence of a vectoral error signal, while the latter is less restrictive, and requires at least a scalar evaluator. We will look for the existence of candidate error or evaluator signals in the cortex and basal ganglia during force-field learning where the motor error is task-relevant and explicitly provided to the subject. By simultaneously recording large populations of neurons from multiple brain areas we can probe the existence of error or evaluator signals by measuring the stochastic relationship and predictive ability of neural activity to the provided error signal. From this data we will also be able to track dependence of neural tuning trajectory on trial-by-trial success; if the cortex operates under minimization principles, then tuning change will have a temporal relationship to reward. The overarching goal of this research is to look for one aspect of motor learning – the error signal – with the hope of using this data to better understand the normal function of the cortex and basal ganglia, and how this normal function is related to the symptoms caused by disease and lesions of the brain.

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ref: Stapleton-2006.04 tags: Stapleton Lavine poisson prediction gustatory discrimination statistical_model rats bayes BUGS date: 0-0-2006 0:0 revision:0 [head]



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ref: notes-0 tags: linux rename files add extension date: 0-0-2006 0:0 revision:0 [head]

pretty simple, to add a .mp3 to all files in a directory (e.g. if they originally were on an old mac):

     rename 's/(.*)/$1.mp3/' *
the expression in quotes is just a perl regular expression