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

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

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

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

[0] Ashe J, Force and the motor cortex.Behav Brain Res 87:2, 255-69 (1997 Sep)[1] 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)[2] Cheney PD, Fetz EE, Functional classes of primate corticomotoneuronal cells and their relation to active force.J Neurophysiol 44:4, 773-91 (1980 Oct)[3] Evarts EV, Relation of pyramidal tract activity to force exerted during voluntary movement.J Neurophysiol 31:1, 14-27 (1968 Jan)[4] Evarts EV, Activity of pyramidal tract neurons during postural fixation.J Neurophysiol 32:3, 375-85 (1969 May)[5] Humphrey DR, Schmidt EM, Thompson WD, Predicting measures of motor performance from multiple cortical spike trains.Science 170:959, 758-62 (1970 Nov 13)[6] Thach WT, Correlation of neural discharge with pattern and force of muscular activity, joint position, and direction of intended next movement in motor cortex and cerebellum.J Neurophysiol 41:3, 654-76 (1978 May)[7] Wetts R, Kalaska JF, Smith AM, Cerebellar nuclear cell activity during antagonist cocontraction and reciprocal inhibition of forearm muscles.J Neurophysiol 54:2, 231-44 (1985 Aug)[8] Georgopoulos AP, Ashe J, Smyrnis N, Taira M, The motor cortex and the coding of force.Science 256:5064, 1692-5 (1992 Jun 19)[9] Kalaska JF, Cohen DA, Hyde ML, Prud'homme M, A comparison of movement direction-related versus load direction-related activity in primate motor cortex, using a two-dimensional reaching task.J Neurosci 9:6, 2080-102 (1989 Jun)[10] 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)[11] 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)[12] Sergio LE, Kalaska JF, Systematic changes in motor cortex cell activity with arm posture during directional isometric force generation.J Neurophysiol 89:1, 212-28 (2003 Jan)[13] Taira M, Boline J, Smyrnis N, Georgopoulos AP, Ashe J, On the relations between single cell activity in the motor cortex and the direction and magnitude of three-dimensional static isometric force.Exp Brain Res 109:3, 367-76 (1996 Jun)[14] Maier MA, Bennett KM, Hepp-Reymond MC, Lemon RN, Contribution of the monkey corticomotoneuronal system to the control of force in precision grip.J Neurophysiol 69:3, 772-85 (1993 Mar)[15] Hepp-Reymond M, Kirkpatrick-Tanner M, Gabernet L, Qi HX, Weber B, Context-dependent force coding in motor and premotor cortical areas.Exp Brain Res 128:1-2, 123-33 (1999 Sep)[16] Smith AM, Hepp-Reymond MC, Wyss UR, Relation of activity in precentral cortical neurons to force and rate of force change during isometric contractions of finger muscles.Exp Brain Res 23:3, 315-32 (1975 Sep 29)[17] Cooke JD, Brown SH, Movement-related phasic muscle activation. II. Generation and functional role of the triphasic pattern.J Neurophysiol 63:3, 465-72 (1990 Mar)[18] Almeida GL, Hong DA, Corcos D, Gottlieb GL, Organizing principles for voluntary movement: extending single-joint rules.J Neurophysiol 74:4, 1374-81 (1995 Oct)[19] Gottlieb GL, Latash ML, Corcos DM, Liubinskas TJ, Agarwal GC, Organizing principles for single joint movements: V. Agonist-antagonist interactions.J Neurophysiol 67:6, 1417-27 (1992 Jun)[20] Corcos DM, Agarwal GC, Flaherty BP, Gottlieb GL, Organizing principles for single-joint movements. IV. Implications for isometric contractions.J Neurophysiol 64:3, 1033-42 (1990 Sep)[21] Gottlieb GL, Corcos DM, Agarwal GC, Latash ML, Organizing principles for single joint movements. III. Speed-insensitive strategy as a default.J Neurophysiol 63:3, 625-36 (1990 Mar)[22] Corcos DM, Gottlieb GL, Agarwal GC, Organizing principles for single-joint movements. II. 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[0] Matsuzaka Y, Picard N, Strick PL, Skill representation in the primary motor cortex after long-term practice.J Neurophysiol 97:2, 1819-32 (2007 Feb)

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[0] 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)[1] Caminiti R, Johnson PB, Urbano A, Making arm movements within different parts of space: dynamic aspects in the primate motor cortex.J Neurosci 10:7, 2039-58 (1990 Jul)

[0] Maravita A, Iriki A, Tools for the body (schema).Trends Cogn Sci 8:2, 79-86 (2004 Feb)[1] Iriki A, Tanaka M, Iwamura Y, Coding of modified body schema during tool use by macaque postcentral neurones.Neuroreport 7:14, 2325-30 (1996 Oct 2)

[0] Narayanan NS, Kimchi EY, Laubach M, Redundancy and synergy of neuronal ensembles in motor cortex.J Neurosci 25:17, 4207-16 (2005 Apr 27)

[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] Francis JT, Influence of the inter-reach-interval on motor learning.Exp Brain Res 167:1, 128-31 (2005 Nov)

[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] Boline J, Ashe J, On the relations between single cell activity in the motor cortex and the direction and magnitude of three-dimensional dynamic isometric force.Exp Brain Res 167:2, 148-59 (2005 Nov)

[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] Sergio LE, Hamel-Paquet C, Kalaska JF, Motor cortex neural correlates of output kinematics and kinetics during isometric-force and arm-reaching tasks.J Neurophysiol 94:4, 2353-78 (2005 Oct)[1] Hatsopoulos NG, Encoding in the motor cortex: was evarts right after all? Focus on "motor cortex neural correlates of output kinematics and kinetics during isometric-force and arm-reaching tasks".J Neurophysiol 94:4, 2261-2 (2005 Oct)[2] Cooke JD, Brown SH, Movement-related phasic muscle activation. II. Generation and functional role of the triphasic pattern.J Neurophysiol 63:3, 465-72 (1990 Mar)[3] Almeida GL, Hong DA, Corcos D, Gottlieb GL, Organizing principles for voluntary movement: extending single-joint rules.J Neurophysiol 74:4, 1374-81 (1995 Oct)[4] Gottlieb GL, Latash ML, Corcos DM, Liubinskas TJ, Agarwal GC, Organizing principles for single joint movements: V. Agonist-antagonist interactions.J Neurophysiol 67:6, 1417-27 (1992 Jun)[5] Corcos DM, Agarwal GC, Flaherty BP, Gottlieb GL, Organizing principles for single-joint movements. IV. Implications for isometric contractions.J Neurophysiol 64:3, 1033-42 (1990 Sep)[6] Gottlieb GL, Corcos DM, Agarwal GC, Latash ML, Organizing principles for single joint movements. III. Speed-insensitive strategy as a default.J Neurophysiol 63:3, 625-36 (1990 Mar)[7] Corcos DM, Gottlieb GL, Agarwal GC, Organizing principles for single-joint movements. II. A speed-sensitive strategy.J Neurophysiol 62:2, 358-68 (1989 Aug)[8] Gottlieb GL, Corcos DM, Agarwal GC, Organizing principles for single-joint movements. I. A speed-insensitive strategy.J Neurophysiol 62:2, 342-57 (1989 Aug)[9] Ghez C, Gordon J, Trajectory control in targeted force impulses. I. Role of opposing muscles.Exp Brain Res 67:2, 225-40 (1987)[10] Sainburg RL, Ghez C, Kalakanis D, Intersegmental dynamics are controlled by sequential anticipatory, error correction, and postural mechanisms.J Neurophysiol 81:3, 1045-56 (1999 Mar)

[0] Hatsopoulos NG, Encoding in the motor cortex: was evarts right after all? Focus on "motor cortex neural correlates of output kinematics and kinetics during isometric-force and arm-reaching tasks".J Neurophysiol 94:4, 2261-2 (2005 Oct)

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

[0] Maier MA, Bennett KM, Hepp-Reymond MC, Lemon RN, Contribution of the monkey corticomotoneuronal system to the control of force in precision grip.J Neurophysiol 69:3, 772-85 (1993 Mar)[1] Smith AM, Hepp-Reymond MC, Wyss UR, Relation of activity in precentral cortical neurons to force and rate of force change during isometric contractions of finger muscles.Exp Brain Res 23:3, 315-32 (1975 Sep 29)

[0] Hepp-Reymond M, Kirkpatrick-Tanner M, Gabernet L, Qi HX, Weber B, Context-dependent force coding in motor and premotor cortical areas.Exp Brain Res 128:1-2, 123-33 (1999 Sep)

[0] Caminiti R, Johnson PB, Galli C, Ferraina S, Burnod Y, Making arm movements within different parts of space: the premotor and motor cortical representation of a coordinate system for reaching to visual targets.J Neurosci 11:5, 1182-97 (1991 May)

[0] Caminiti R, Johnson PB, Urbano A, Making arm movements within different parts of space: dynamic aspects in the primate motor cortex.J Neurosci 10:7, 2039-58 (1990 Jul)[1] Caminiti R, Johnson PB, Galli C, Ferraina S, Burnod Y, Making arm movements within different parts of space: the premotor and motor cortical representation of a coordinate system for reaching to visual targets.J Neurosci 11:5, 1182-97 (1991 May)

[0] Kalaska JF, Cohen DA, Hyde ML, Prud'homme M, A comparison of movement direction-related versus load direction-related activity in primate motor cortex, using a two-dimensional reaching task.J Neurosci 9:6, 2080-102 (1989 Jun)

[0] Georgopoulos AP, Ashe J, Smyrnis N, Taira M, The motor cortex and the coding of force.Science 256:5064, 1692-5 (1992 Jun 19)

[0] Wetts R, Kalaska JF, Smith AM, Cerebellar nuclear cell activity during antagonist cocontraction and reciprocal inhibition of forearm muscles.J Neurophysiol 54:2, 231-44 (1985 Aug)

[0] Thach WT, Correlation of neural discharge with pattern and force of muscular activity, joint position, and direction of intended next movement in motor cortex and cerebellum.J Neurophysiol 41:3, 654-76 (1978 May)

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

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

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

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[0] Ferrari PF, Rozzi S, Fogassi L, Mirror neurons responding to observation of actions made with tools in monkey ventral premotor cortex.J Cogn Neurosci 17:2, 212-26 (2005 Feb)

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

PMID-27225074 Somatostatin-expressing neurons in cortical networks.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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


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

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

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

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


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

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

Aqueous degradation of polyimides

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

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

Physical Metallurgy of Refactory Metals and Alloys

Properties of tungsten-rhenium alloys

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

PMID-23900251 Parallel super-resolution imaging

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

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

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

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


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

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

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

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

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

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

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

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

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

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

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

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

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


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

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

PMID-24187539 Physical principles for scalable neural recording.

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

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

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

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

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

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

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

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

Biomechanics of substrate boring by fig wasps

  • Lakshminath Kundanati and Namrata Gundiah 2014

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


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

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

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

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

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

A damage-tolerant glass

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

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

ImageNet Classification with Deep Convolutional Networks

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

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

#!/usr/bin/perl -w

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

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

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

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


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

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

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

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

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ref: -0 tags: DBS dystonia globus pallidus witt date: 10-05-2013 23:42 gmt revision:2 [1] [0] [head]

PMID-23549056 Use of pallidal deep brain stimulation in postinfarct hemidystonia.

  • Witt J, Starr PA, Ostrem JL. 2013
  • Result: GPi DBS generates subjective improvements in movement after surgery;
  • However, one year after implantation, no effect could be measured.
  • See also: {1263}

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ref: -0 tags: DBS dystonia trial globus pallidus GPI witt date: 10-05-2013 23:41 gmt revision:1 [0] [head]

PMID-23787946 Predictive factors of outcome in primary cervical dystonia following pallidal deep brain stimulation.

  • Witt JL, Moro E, Ash RS, Hamani C, Starr PA, Lozano AM, Hodaie M, Poon YY, Markun LC, Ostrem JL. 2013
  • Some of the treatments do work, but the authors were unsuccessful in determining criteria to suggest proper candidates.

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ref: -0 tags: DBS dystonia starr date: 10-05-2013 22:42 gmt revision:0 [head]

PMID-17618522 Pallidal deep brain stimulation in patients with cranial-cervical dystonia (Meige syndrome).

  • Ostrem JL, Marks WJ Jr, Volz MM, Heath SL, Starr PA. 2007
  • Six patients underwent bilateral stereotactic implantation of DBS leads into the sensorimotor GPi.
  • Patients were evaluated with the Burke-Fahn-Marsden dystonia rating scale (BFMDRS) and Toronto western spamodic torticollis rating scale (TWSTRS) before surgery and 6 months postoperatively.
  • At 6 months, patients showed a 72% mean improvement in the BFMDRS total movement score (P < 0.028, Wilcoxin signed rank test).
  • Despite improvement in dystonia, mild worsening of motor function was reported in previously nondystonic body regions with stimulation in 4 patients.
  • Although GPi DBS was effective in these patients, the influence of GPi DBS on nondystonic body regions deserves further investigation.

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

PMID-17848864 Deep brain stimulation

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

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

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

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

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

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

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

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

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

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


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

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

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

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

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

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

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

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

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

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

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

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

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

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


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

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

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

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ref: Yuen-1995.08 tags: stab wound histology rabbits date: 01-29-2013 03:56 gmt revision:1 [0] [head]

PMID-8562785[0] Histological evaluation of polyesterimide-insulated gold wires in brain.

  • no evidence of needle pull-through (stab wound) in rabbits


[0] Yuen TG, Agnew WF, Histological evaluation of polyesterimide-insulated gold wires in brain.Biomaterials 16:12, 951-6 (1995 Aug)

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

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

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


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

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

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

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


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

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

Things to read!


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


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

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

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

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


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

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

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

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

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

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

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


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

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

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

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


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

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

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

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


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

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

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

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


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

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

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

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


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

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

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

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


fiber diametercapsule thickness


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

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

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

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


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

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

PMID-7814435 Fate and biocompatibility of three types of microspheres implanted into the brain.

  • microspheres ( 24μm ) appear to be engulfed or surrounded by histocytic cells.
  • poly(e-caprolactone), which is supposed to be biodegradable, did not dissolve in the brain. The polymer is hydrophobic.
  • 20um spheres could be engulfed by macrophages; their microspheres were too large, and were encapsulated in a thin coallagen layer and astrocytic process.
  • no scale bars - annoying - but we can estimate the size of the coating to be about the same size as the beads themselves.

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ref: Stensaas-1976.01 tags: histology implant electrodes immune response date: 01-25-2013 02:52 gmt revision:1 [0] [head]

PMID-782142[0] The reaction of the cerebral cortex to chronically implanted plastic needles.

  • Three different classes of result:
    • Type I is characterized by little or no gliosis and synapses within 1-5mu of the implant;
    • type II contains a pronounced zone of reactive astrocytes;
    • type III is typified by a zone of connective tissue near the implant surface
      • One implant can evince all 3 different types!
  • Already were thinking of neuroprosthetic devices.


[0] Stensaas SS, Stensaas LJ, The reaction of the cerebral cortex to chronically implanted plastic needles.Acta Neuropathol 35:3, 187-203 (1976)

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ref: Skousen-2011.01 tags: electrodes immune response Tresco Wise Michigan histology GFAP atrocyte surface area foreign body response date: 01-25-2013 01:44 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-21867802[0] Reducing surface area while maintaining implant penetrating profile lowers the brain foreign body response to chronically implanted planar silicon microelectrode arrays.

  • We studied the chronic brain foreign body response to planar solid silicon microelectrode arrays and planar lattice arrays with identical penetrating profiles but with reduced surface area in rats after an 8-week indwelling period.
  • Using quantitative immunohistochemistry, we found that presenting less surface area after equivalent iatrogenic injury is accompanied by significantly less
    • persistent macrophage activation,
    • decreased blood brain barrier leakiness,
    • and reduced neuronal cell loss.
  • Could be a factor of micromotion, too -- the lattice array has more anchoring points (?)
  • They propose it's a factor of TNF- α concentration around the implants. This, and other proinflammatory and cytoxic cytokines, is released by macrophages.
  • "Recent studies from our lab have described disruption of BBB integrity, indicated by the presence of autologous IgG in the brain parenchyma, surrounding both microwire and planar silicon recording devices ([1][2]. Under normal conditions, autologous IgG is excluded from the brain parenchyma (Azzi et al., 1990; Seitz et al., 1985) but has been observed following BBB disruption (Aihara et al., 1994).
    • E.g. the presence of IgG proves that the BBB was compromised.
      • Less so with the lattice implants.
  • Previous work from our lab using single microwires and single shaft, planar silicon microelectrode arrays indicated that the spatial distribution of GFAP does not increase with time over the indwelling period and did not support the “increase in astrogliosis over time hypothesis” as a dominant or general biologically related failure mechanism for this type of microelectrode recording device {1197}.


[0] Skousen JL, Merriam SM, Srivannavit O, Perlin G, Wise KD, Tresco PA, Reducing surface area while maintaining implant penetrating profile lowers the brain foreign body response to chronically implanted planar silicon microelectrode arrays.Prog Brain Res 194no Issue 167-80 (2011)
[1] Winslow BD, Christensen MB, Yang WK, Solzbacher F, Tresco PA, A comparison of the tissue response to chronically implanted Parylene-C-coated and uncoated planar silicon microelectrode arrays in rat cortex.Biomaterials 31:35, 9163-72 (2010 Dec)
[2] Winslow BD, Tresco PA, Quantitative analysis of the tissue response to chronically implanted microwire electrodes in rat cortex.Biomaterials 31:7, 1558-67 (2010 Mar)

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

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

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


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

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

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

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


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

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

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

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

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ref: Thelin-2011.01 tags: histology MEA tether tissue response malmo lund date: 01-24-2013 22:17 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-21298109[0] Implant size and fixation mode strongly influence tissue reactions in the CNS.

  • Overview: tethering and size both increase immune response, and causes continued GFAP activity.
    • An untethered 50um electrode exhibited very weak inflammatory response after 12 weeks.
      • Suggesting that a small electrode can move with the brain.
  • Tethering in their context means affixed rigidly to the bone.
    • Small-diameter, untethered implants cause the smallest tissue reactions.
    • Likely that this scales.
  • Stice et al 2007 {1111} -- GFAP expression was significantly smaller for 12 um diameter implants than 25um implants @ 4 weeks.
  • They used 50um and 200um stainless steel implants.
    • implants glued to micromanipulator using gelatine
  • 24 rats.
  • Much more GFAP and ED1 actviity in tethered implants; NEuN neural density about the same.
  • 50um implant had a higher NeuN + count.
  • Regarding implantation: not sure. Have to find a reference for stab wounds (where the inserter is retracted).


[0] Thelin J, Jörntell H, Psouni E, Garwicz M, Schouenborg J, Danielsen N, Linsmeier CE, Implant size and fixation mode strongly influence tissue reactions in the CNS.PLoS One 6:1, e16267 (2011 Jan 26)

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

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

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


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

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ref: Biran-2005.09 tags: microelectrode Michigan probe glia tissue response electrode immune histology MEA Biran date: 01-24-2013 20:49 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-16045910[0] Neuronal cell loss accompanies the brain tissue response to chronically implanted silicon microelectrode arrays.

  • See also {1190} (wow, I'm redundant!)
  • Important point: ED1 up-regulation and neuronal loss were not observed in microelectrode stab controls, indicating that the phenotype did not result from the initial mechanical trauma of electrode implantation, but was associated with the foreign body response.
    • CD68 = ED1 is a marker for microglia and other macrophages. (wikipedia article is informative).
    • GFAP = glial fibrillary acidic protein, marker for astrocytes.
  • Recording failure is caused by chronic inflammation (mostly activated microglia) at the microelectrode brain tissue interface.
  • Only tested response 2 and 4 weeks after implantation. Makes sense for stab wound, but didn't the want to see a longer term response? Or do their electrodes just not last that long?
  • What did they coat the silicon probes in?
  • Used silastic to shock-mount their floating electrodes, but this apparently made no difference compared to conventional dental cement and bone screw mounting.
  • Suggest that chronic inflammatory response may be related to the absorption of fibrogen and complement to the surface of the device (device should not be porous?), the subsequent release of pro-inflammatory and cytotoxic cytokines by activated microphages, and the persistence of activated macrophages around materials which cannot be broken down.
    • Well then, how do you make the electrodes biochemically / biologically 'invisible'?
    • Persistently activated microglia are found around insoluble plaques in AD (plaques that cannot be / are not removed from the brain via proteolysis. Microglia form 'glitter cells' when they engulf undigestible stubstances). This has been termed 'frustrated phagocytosis', which results in increased secretion of proinflamatory cytokines that directly or indirectly cause neuronal death.
  • Significant reductions in neurofiliament reactivity was seen up to 230um from the microelectrode interface; this was not seen for stab wounds. Maximum recording distance is about 130um; 100um more reasonable in normal conditions.
  • Accumulating evidence from postmortem analysis of patients implanted with DBS electrodes reveals that chronic neuroinflamation is part of the response to such (duller, larger) implants as well. They have seen cell loss up to 1mm fromt the electrode surface here.


[0] Biran R, Martin DC, Tresco PA, Neuronal cell loss accompanies the brain tissue response to chronically implanted silicon microelectrode arrays.Exp Neurol 195:1, 115-26 (2005 Sep)

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ref: -0 tags: histology atryocytes immune response electrode arrays lund multiple exacerbate date: 01-24-2013 19:56 gmt revision:1 [0] [head]

PMID-23091629 Multiple implants do not aggravate the tissue reaction in rat brain.

  • After six weeks, the astrocytic scar surrounding the middle out of five implants was significantly smaller compared to the single contralateral implant, suggesting that an intrahemispheric interaction might be taking place, reducing the astrocytic response around the central implant.
  • Weak (?) staining for ED1 in this study?
  • -- after 6 weeks.
  • Thought: every paper has a different method for quantify immune response, GFAP staining in this case.

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ref: COLLIAS-1957.05 tags: histology microelectrode vasulature date: 01-23-2013 23:56 gmt revision:4 [3] [2] [1] [0] [head]

PMID-13429398[0] Histopathological changes produced by implanted electrodes in cat brains; comparison with histopathological changes in human and experimental puncture wounds.

  • Quite a good and overcomplete / long article -- fully describes their result of implanting bundles of 0.005" varnished steel wires into the brains of cats.
    • Saw hemorrhagic necrosis, necrosis from edema, and eventual encapsulation and collapse of capilaries around the chronic implant. All things that we still have to contend with.
  • From [1]: ... For single penetrating electrodes into cat cortex, Collias and Manuelidis noted and increase in hemorrhagic damage near electrode tracks of the cortex nearest the point of electrode entry into the pia.
  • They also reported that the damage appeared to be randomly distributed among the implants, which they attributed to differences in local vasculature.
  • The toxicity of certain metals, namely, platinum, platinum-8% tungsten, platinum-10% rhodium, platinum-10% iridium, platinum-10% nickel, platinized platinum, a gold-nickel-chromium alloy, a gold-palladium-rhodium alloy, a chromium-nickel-molybdenum alloy (Vitallium), stainless steel, silver, rhenium, and gold, was evaluated histologically following chronic implantation for 2 months in the brains of cats. Of the above metals, all but silver were found to be nontoxic. Boron was also evaluated and found to be nontoxic.


[0] COLLIAS JC, MANUELIDIS EE, Histopathological changes produced by implanted electrodes in cat brains; comparison with histopathological changes in human and experimental puncture wounds.J Neurosurg 14:3, 302-28 (1957 May)
[1] Rousche PJ, Normann RA, Chronic recording capability of the Utah Intracortical Electrode Array in cat sensory cortex.J Neurosci Methods 82:1, 1-15 (1998 Jul 1)

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

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

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

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ref: Gilletti-2006.09 tags: electrode micromotion histology GFAP variable reluctance date: 01-04-2013 02:28 gmt revision:2 [1] [0] [head]

PMID-16921202[0] Brain micromotion around implants in the rodent somatosensory cortex.

  • Used a differential variable reluctance transducer (DVRT) in adult rats (n = 6) to monitor micromotion normal to the somatosensory cortex surface
    • Reluctance e.g. AC inductance varied with a floating bobbin (or so -- they do not list the details of this COTS device).
  • Pulsatile surface micromotion was observed to be in the order of 10-30 um due to pressure changes during respiration and 2-4 um due to vascular pulsatility.
  • Large inward displacements of brain tissue between 10-60 um were observed in n = 3 animals immediately following the administration of anesthesia


[0] Gilletti A, Muthuswamy J, Brain micromotion around implants in the rodent somatosensory cortex.J Neural Eng 3:3, 189-95 (2006 Sep)

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ref: Biran-2005.09 tags: Tresco histology chronic implantation astrocytes microglia date: 01-04-2013 02:28 gmt revision:3 [2] [1] [0] [head]

PMID-16045910[0] Neuronal cell loss accompanies the brain tissue response to chronically implanted silicon microelectrode arrays.

  • We observed persistent ED1 immunoreactivity around implanted silicon microelectrode arrays implanted in adult rat cortex that was accompanied by a significant reduction in nerve fiber density and nerve cell bodies in the tissue immediately surrounding the implanted silicon microelectrode arrays.
  • We found that explanted electrodes were covered with ED1/MAC-1 immunoreactive cells and that the cells released MCP-1 and TNF-a under serum-free conditions in vitro.
  • See also [1] and [2]
  • Electrodes: Michigan type, 5mm long, 200um wide tapering to 30um, 15um thick at the shank tapering to 2um.
    • Show that the chronic response is markedly different than acute stab wounds.
    • "Stab wounds resulted in comparatively minimal neurofilament loss at 2 weeks (A) and no apparent loss by 4 weeks".
    • "The number of neuronal bodies is reduced in the area adjacent to microelectrodes (B, D) but appears unaltered surrounding stab wound lesions (A, C; lesion site in center of each image)."
  • Includes details of immunostaining, which could be useful.


[0] Biran R, Martin DC, Tresco PA, Neuronal cell loss accompanies the brain tissue response to chronically implanted silicon microelectrode arrays.Exp Neurol 195:1, 115-26 (2005 Sep)
[1] Szarowski DH, Andersen MD, Retterer S, Spence AJ, Isaacson M, Craighead HG, Turner JN, Shain W, Brain responses to micro-machined silicon devices.Brain Res 983:1-2, 23-35 (2003 Sep 5)
[2] Gilletti A, Muthuswamy J, Brain micromotion around implants in the rodent somatosensory cortex.J Neural Eng 3:3, 189-95 (2006 Sep)

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

PMID-22163863 Recent advances in neural recording microsystems.

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

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

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

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

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

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

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

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

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

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

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ref: -0 tags: Hinton google tech talk dropout deep neural networks Boltzmann date: 11-09-2012 18:01 gmt revision:0 [head]


  • Hinton believes in the the power of crowds -- he thinks that the brain fits many, many different models to the data, then selects afterward.
    • Random forests, as used in predator, is an example of this: they average many simple to fit and simple to run decision trees. (is apparently what Kinect does)
  • Talk focuses on dropout, a clever new form of model averaging where only half of the units in the hidden layers are trained for a given example.
    • He is inspired by biological evolution, where sexual reproduction often spontaneously adds or removes genes, hence individual genes or small linked genes must be self-sufficient. This equates to a 'rugged individualism' of units.
    • Likewise, dropout forces neurons to be robust to the loss of co-workers.
    • This is also great for parallelization: each unit or sub-network can be trained independently, on it's own core, with little need for communication! Later, the units can be combined via genetic algorithms then re-trained.
  • Hinton then observes that sending a real value p (output of logistic function) with probability 0.5 is the same as sending 0.5 with probability p. Hence, it makes sense to try pure binary neurons, like biological neurons in the brain.
    • Indeed, if you replace the backpropagation with single bit propagation, the resulting neural network is trained more slowly and needs to be bigger, but it generalizes better.
    • Neurons (allegedly) do something very similar to this by poisson spiking. Hinton claims this is the right thing to do (rather than sending real numbers via precise spike timing) if you want to robustly fit models to data.
      • Sending stochastic spikes is a very good way to average over the large number of models fit to incoming data.
      • Yes but this really explains little in neuroscience...
  • Paper referred to in intro: Livnat, Papadimitriou and Feldman, PMID-19073912 and later by the same authors PMID-20080594

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

List of links from Moshe Looks google tech talk:

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ref: Chen-2004.08 tags: brain phantoms agar agarose proxy date: 07-13-2012 01:39 gmt revision:3 [2] [1] [0] [head]

Regarding brain phantoms:


Also, both hydrophilic and hydrophobic cleaning appears to be superior to bare tungsten, with the hydrophillic surface treatment slightly superior -- PMID-16686416[2]


[0] Chen ZJ, Gillies GT, Broaddus WC, Prabhu SS, Fillmore H, Mitchell RM, Corwin FD, Fatouros PP, A realistic brain tissue phantom for intraparenchymal infusion studies.J Neurosurg 101:2, 314-22 (2004 Aug)
[1] Ritter RC, Quate EG, Gillies GT, Grady MS, Howard MA 3rd, Broaddus WC, Measurement of friction on straight catheters in in vitro brain and phantom material.IEEE Trans Biomed Eng 45:4, 476-85 (1998 Apr)
[2] Jensen W, Yoshida K, Hofmann UG, In-vivo implant mechanics of flexible, silicon-based ACREO microelectrode arrays in rat cerebral cortex.IEEE Trans Biomed Eng 53:5, 934-40 (2006 May)

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ref: Freire-2011.01 tags: Nicolelis BMI electrodes immune respones immunohistochemistry chronic arrays rats 2011 MEA histology date: 06-29-2012 01:20 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-22096594[0] Comprehensive analysis of tissue preservation and recording quality from chronic multielectrode implants.

  • Says what might be expected: tungsten microelectrode arrays work, though the quality gradually declines over 6 months.
  • Histological markers correlated well with recording performance.
  • Shows persistent glial activation around electrode sites + cell body hypertropy.
    • Suggest that loss in recording quality may be due to glial encapsulation.
  • References
    • Szarowski et al 2003 {1028}
    • Ward et al 2009
  • Histology:
    • NADPH-d: nicotinamide adenine dinucleotide phosphate-diaphorase, via beta-NADP
    • CO: cytochrome oxidase, via diamnibenzidine DAB, cytochrome c and catalase.
      • both good for staining cortical layers; applied in a standard buffered solution and monitored to prevent overstaining.
  • Immunohistochemistry:
    • Activated microglia with ED-1 antibody.
    • Astrocytes labeled with glial fibrillary acid protein.
    • IEG with an antibody against EGR-1, 'a well-known marker of calcium dependent neuronal activity'
    • Neurofilament revealed using a monoclonal NF-M antibody.
    • Caspace-3 with the associated antibody
    • Details the steps for immunostaining -- wash, blocknig buffer, addition of the antibody in diluted blocking solution (skim milk) overnight, wash again, incubate in biotinylated secondary antibody, wash again, incubate in avidin-biotin-peroxidase solution.
    • Flourescent immunohistochemistry had biotynlation replaced with alexa Fluor 488-conjugated horse anti-mouse and Alexa Fluor 594-conjugated goat anti-rabbit overnight.


[0] Freire MA, Morya E, Faber J, Santos JR, Guimaraes JS, Lemos NA, Sameshima K, Pereira A, Ribeiro S, Nicolelis MA, Comprehensive analysis of tissue preservation and recording quality from chronic multielectrode implants.PLoS One 6:11, e27554 (2011)

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

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

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


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

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

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

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

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

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

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

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

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

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

PMID-2479133 The functional anatomy of basal ganglia disorders.

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

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


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

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

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

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

My thoughts:

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


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

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ref: Starr-2005.06 tags: STN DBS MPTP UCSF dystonia date: 02-28-2012 17:59 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-15703229[0] Spontaneous pallidal neuronal activity in human dystonia: comparison with Parkinson's disease and normal macaque.

  • both dystonia and PD.
  • Several firing rate changes:
    • dystonic patients showed decreased GPI firing.
    • PD patients showed higher pallidial discharge
    • GPi discharge rate was inversely correlated with dystonia severity.
  • Control with recordings from normal monkeys.
  • GPi showed increased oscillatory activity in the 2- to 10-Hz range (theta) and increased bursting activity in both dystonia and PD as compared with the normal NHPs.


[0] Starr PA, Rau GM, Davis V, Marks WJ Jr, Ostrem JL, Simmons D, Lindsey N, Turner RS, Spontaneous pallidal neuronal activity in human dystonia: comparison with Parkinson's disease and normal macaque.J Neurophysiol 93:6, 3165-76 (2005 Jun)

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ref: -0 tags: dopamine reward prediction striatum error striatum orbitofrontal reward date: 02-24-2012 21:26 gmt revision:1 [0] [head]

PMID-11105648 Involvement of basal ganglia and orbitofrontal cortex in goal-directed behavior.

  • Many regions have a complex set of activations, but dopamine neurons appear more homogenous: they report the error in reward prediction.
    • "The homogeneity of responsiveness across the population of dopamine neurons indicates that this error signal is widely broadcast to dopamine terminal regions where it could provide a teaching signal for synaptic modifications underlying the learning of goal-directed appetitive behaviors."
    • Signals are not contingent on the type of behavior needed to obtain the reward, and hence represent a relatively 'pure' reward prediction error.
  • Unlike dopamine neurons, many striatal neurons respond to predicted rewards, although at least some may reflect the relative degree of predictability in the magnitude of the responses to reward.
  • Neuronal activations in the orbitofrontal cortex appear to involve less integration of behavioral and reward-related information, but rather incorporate another aspect of reward, the relative motivational significance of different rewards.
  • Processing is hierarchical (or supposed to be so):
    • Dopamine neurons provide a relatively pure signal of an error in reward prediction,
    • Striatal neurons signal not only reward, but also behavioral contingencies,
    • Orbitofrontal neurons signal reward and incorporate relative reward preference.

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

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

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

Old notes:

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


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

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

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

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


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ref: Benabid-2009.01 tags: DBS historical perspective date: 02-22-2012 14:54 gmt revision:2 [1] [0] [head]

PMID-19660668[0] Functional neurosurgery for movement disorders: a historical perspective.

  • Spinal cord LFS (30 Hz) has been used to treat intractible pain for decades.
  • Based on experimental data obtained in MPTP-treated parkinsonian monkeys, the pedunculopontine nucleus has been used as a new target, and as suggested by the animal research results, its use indeed improves walking and stability when stimulation is performed at low frequency (25 Hz).
    • But donesn't it induce feelings of well-being {1074}
  • On freezing gait, which is non-dopamergic and not treated via STN DBS:
    • Based on experimental data obtained in MPTP-treated parkinsonian monkeys, the pedunculopontine nucleus has been used as a new target, and as suggested by the animal research results, its use indeed improves walking and stability when stimulation is performed at low frequency (25 Hz)
  • Many channel IPGS can target multiple structures with multiple frequencies; author thinks this is the future in terms of efficiency.
  • Suggests brain-machine interfaces (?)


[0] Benabid AL, Chabardes S, Torres N, Piallat B, Krack P, Fraix V, Pollak P, Functional neurosurgery for movement disorders: a historical perspective.Prog Brain Res 175no Issue 379-91 (2009)

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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) where U rh is the rheobase and t ch is the chronaxie.
    • you can simplify this to: I th=I rh(1+t cht) where I rh is the rheobase current and I 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 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: Turner-2010.12 tags: STN DBS basal ganglia motor learning vigor scaling review date: 02-16-2012 21:27 gmt revision:3 [2] [1] [0] [head]

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

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


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

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ref: work-2999 tags: autocorrelation poisson process test neural data ISI synchrony DBS date: 02-16-2012 17:53 gmt revision:5 [4] [3] [2] [1] [0] [head]

I recently wrote a matlab script to measure & plot the autocorrelation of a spike train; to test it, I generated a series of timestamps from a homogeneous Poisson process:

function [x, isi]= homopoisson(length, rate)
% function [x, isi]= homopoisson(length, rate)
% generate an instance of a poisson point process, unbinned.
% length in seconds, rate in spikes/sec. 
% x is the timestamps, isi is the intervals between them.

num = length * rate * 3; 
isi = -(1/rate).*log(1-rand(num, 1)); 
x = cumsum(isi); 
%%find the x that is greater than length. 
index = find(x > length); 
x = x(1:index(1,1)-1, 1); 
isi = isi(1:index(1,1)-1, 1); 

The autocorrelation of a Poisson process is, as it should be, flat:


  • Red lines are the autocorrelations estimated from shuffled timestamps (e.g. measure the ISIs - interspike intervals - shuffle these, and take the cumsum to generate a new series of timestamps). Hence, red lines are a type of control.
  • Blue lines are the autocorrelations estimated from segments of the full timestamp series. They are used to how stable the autocorrelation is over the recording
  • Black line is the actual autocorrelation estimated from the full timestamp series.

The problem with my recordings is that there is generally high long-range correlation, correlation which is destroyed by shuffling.

Above is a plot of 1/isi for a noise channel with very high mean 'firing rate' (> 100Hz) in blue. Behind it, in red, is 1/shuffled isi. Noise and changes in the experimental setup (bad!) make the channel very non-stationary.

Above is the autocorrelation plotted in the same way as figure 1. Normally, the firing rate is binned at 100Hz and high-pass filtered at 0.005hz so that long-range correlation is removed, but I turned this off for the plot. Note that the suffled data has a number of different offsets, primarily due to differing long-range correlations / nonstationarities.

Same plot as figure 3, with highpass filtering turned on. Shuffled data still has far more local correlation - why?

The answer seems to be in the relation between individual isis. Shuffling isi order obviuosly does not destroy the distribution of isi, but it does destroy the ordering or pair-wise correlation between isi(n) and isi(n+1). To check this, I plotted these two distributions:

-- Original log(isi(n)) vs. log(isi(n+1)

-- Shuffled log(isi_shuf(n)) vs. log(isi_shuf(n+1)

-- Close-up of log(isi(n)) vs. log(isi(n+1) using alpha-blending for a channel that seems heavily corrupted with electro-cauterizer noise.

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

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

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


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

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

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

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

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ref: Florio-2001.11 tags: STN PPN lesions preparatory rats DBS date: 01-26-2012 17:22 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

PMID-11704255[0] Unilateral lesions of the pedunculopontine nucleus do not alleviate subthalamic nucleus-mediated anticipatory responding in a delayed sensorimotor task in the rat.

  • the title says it all ;)
  • they describe hemiballismus as "stereotyped repetitive involuntary movements of the cotralateral limbs" (might have to see this to understand it)
  • what the rat had to do:
    1. press lever 1 upon trigger 1 stimuli
    2. wait 3-4 seconds for the trigger 2 stimuli
    3. then press lever 2, upon which a pellet of food was given to the rat.
  • lesions of the STN in the rat do not induce hyperkinetic movements in overt behaviors, but cause anticipatory motor responses in delayed-reaction tasks, like a nose-poke.
    • see figure 7 for the bar-graph of this.
    • rats tended to release the lever before the reward or CS for reward was triggered
    • still - this might be a cognitive problem, not a lack of anticipation.
  • the PPN has remarkable reciprocating connections with the STN, and other basal ganglia nuclei
    • PPN lesion increases reaction time during conditioned movements, making the animals bradykinetic or akinetic
      • "the animals bearing the combined lesion were severely impaired in conditioned responding to salient stimuli involved in the paradigm and showed side-specific lengthening of reaction and movement times without global motor impairments."
      • has anybody looked at activity in the PPN of parkinsonian monkeys? hum.
    • compare to [1] - PPN lesions can restore normal activity in SNr & STN. but, if you don't have the STN to restore, then PPN doesn't matter.


[0] Florio T, Capozzo A, Cellini R, Pizzuti G, Staderini EM, Scarnati E, Unilateral lesions of the pedunculopontine nucleus do not alleviate subthalamic nucleus-mediated anticipatory responding in a delayed sensorimotor task in the rat.Behav Brain Res 126:1-2, 93-103 (2001 Nov 29)
[1] Breit S, Lessmann L, Unterbrink D, Popa RC, Gasser T, Schulz JB, Lesion of the pedunculopontine nucleus reverses hyperactivity of the subthalamic nucleus and substantia nigra pars reticulata in a 6-hydroxydopamine rat model.Eur J Neurosci 24:8, 2275-82 (2006 Oct)

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

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

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


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

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

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

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

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ref: Brown-2001.12 tags: EMG ECoG motor control human coherence dopamine oscillations date: 01-19-2012 21:41 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-11765129[0] Cortical network resonance and motor activity in humans.

  • good review.
  • No coherence between ECoG and eMG below 12 Hz; frequency coherence around 18 Hz.
    • This seen only in high-resolution ECoG; lower resolution signals blurs the sharp peak.
  • Striking narrowband frequency of coherence.
  • ECoG - ECoG coherence not at same frequency as EMG-ECoG.
  • Marked task-dependence of these coherences, e.g. for wrist extension and flexion they observed similar EMG/ECoG coherences; for different tasks using the same muscles, different patterns of coherence.
  • Pyramidal cell discharge tends to be phase-locked to oscillations in the local field potential (Murthy and Fetz 1996)
    • All synchronization must ultimately be through spikes, as LFPs are not transmitted down the spinal cord.
  • Broadband coherence is pathological // they note it occurred during cortical myclonus (box 2)
  • Superficial chattering pyramidal cells (!!) firing bursts of frequency at 20 to 80 Hz, interconnected to produce spike doublets (Jefferys 1996).
  • Dopamine restores coherence between EMG and ECoG in a PD patient.


[0] Brown P, Marsden JF, Cortical network resonance and motor activity in humans.Neuroscientist 7:6, 518-27 (2001 Dec)

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ref: Evarts-1968.01 tags: Evarts motor control pyramidal tract M1 PTN tuning date: 01-16-2012 18:59 gmt revision:4 [3] [2] [1] [0] [head]

PMID-4966614[] Relation of pyramidal tract activity to force exerted during voluntary movement

  • PTNs with high conduction velocity tend to be silent during motor quiescence and show phasic activity with movement.
  • PTNs with lower axonal conduction velocities are active in the absence of movement; with movement they show both upward and downward modulations of the resting discharge.
  • many PTNs responded to a conditional stimulus before the movement.
  • in this study, they wanted to determine if phasic response was more correlated with displacement or with force.
    • did this with two different motions (flexion and extension) in two different force loads (opposing flexion and opposing extransion)
      • movements were slow (or at least nonballistic) and somewhat controlled - they had to last between 400 and 700ms.
      • monkeys usually carried out 3,000 cycles of the movement daily !!
  • "prior to the experiment, hte authour was biased to think that the displacement model (where the cortex commands a location/movement of the arm, which is then accomplished through feedback & feedforward mechanisms e.g. in the spinal cord) was correct; experimental results seem to indicate that force is very strongly represented in PTN population.
  • many PTN firing rates reflected dF/dt very strongly.
  • old, good paper. made with 'primitive' technology - but why do we need to redo this?


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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: Schwartz-1994.07 tags: Schwartz drawing spiral monkeys population vector PV date: 01-16-2012 18:52 gmt revision:1 [0] [head]

PMID-8036499[0] Direct cortical representation of drawing


[0] Schwartz AB, Direct cortical representation of drawing.Science 265:5171, 540-2 (1994 Jul 22)

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ref: Leach-2010.02 tags: BMI challenges histology biocompatibility review date: 01-16-2012 18:22 gmt revision:4 [3] [2] [1] [0] [head]

PMID-20161810[0] Bridging the Divide between Neuroprosthetic Design, Tissue Engineering and Neurobiology

  • Neuroprosthetic device technology has seen major advances in recent years but the full potential of these devices remains unrealized due to outstanding challenges, such as the ability to record consistently over long periods of time.
  • Discuss promising new treatments based on developmental and cancer biology (?)
  • Suggest controlled drug release as the tissue is healing. Makes sense.


[0] Leach JB, Achyuta AK, Murthy SK, Bridging the Divide between Neuroprosthetic Design, Tissue Engineering and Neurobiology.Front Neuroeng 2no Issue 18 (2010 Feb 8)

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ref: Wattanapanitch-2007 tags: recording tech amplifier cascode MOS-bipolar pseudoresistor MIT date: 01-15-2012 18:13 gmt revision:5 [4] [3] [2] [1] [0] [head]

IEEE-4358095 (pdf) An Ultra-Low-Power Neural Recording Amplifier and its use in Adaptively-Biased Multi-Amplifier Arrays.

  • images/729_1.pdf -- copy, just in case.
  • Masters thesis - shows the development of, as the title explains, an ultra low power neural amplifier.
  • Probably the best amplifier out there. NEF 2.67; theoretical limit 2.02.
  • Final design uses folded cascode operational transconductance amplifier (OTA)
    • Design employs a capacitor-feedback gain stage of 40db followed by a lowpass stage.
    • Majority of the current is passed through large subthreshold PMOS input transistors.
      • PMOS has lower noise than NMOS in most processes.
      • Subthreshold has the highest transconductance-to-current ratio. (ratio of a ratio)
    • Cascode transistors self-shunt their own current noise sources.
    • Design takes 0.16 mm^2 in 0.5 um AMI CMOS process, uses 2.7 uA from a ~2.8V supply, input referred noise of 3 uVrms
    • Thesis gives all design parameters for the transistors.
    • Input is AC coupled, DC path through gigaohm MOS-bipolar psudoresistor.
      • this path gracefully decays to diode-connected MOS or bipolar transistors if the voltage is high.
    • images/729_1.pdf
  • Last chapter details the use of envelope detection to adaptively change the bias current of the input stage
    • That is, if an electrode is noisy, the bias current is decreased!

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ref: Wyler-1980.05 tags: operant control motor learning interspike intervals ISI Wyler Lange Neafsey Robbins date: 01-07-2012 21:46 gmt revision:1 [0] [head]

PMID-6769536[0] Operant control of precentral neurons: Control of modal interspike intervals

  • Question: can monkeys control the ISI of operantly controlled neurons?
    • Answer: Seems they cannot. Operant and overt movement cells have about the same ISI, and this cannot be changed by conditioning.
  • Task requires a change from tonic to phasic firing, hence they call it "Differential reinforcement of Tonic Patterns".
    • That is, the monkey is trained to produce spikes within a certain ISI window.
    • PDP8 control, applesauce feedback.
    • modal ISI, in this case, means mode (vs. mean and median) of the ISI.
  • Interesting: "It was not uncommon for a neuron to display bi- or trimodal ISI distributions when the monkey was engaged in a movement unrelated to a unit's firing"
  • For 80% of the units, the more tightly a neuron's firing was related to a specific movement, the more gaussian its ISI became.
  • As the monkey gained control over reinforced units, the ISI became more gaussian.
  • Figure 2: monkey was not able to significantly change the modal ISI.
    • Monkeys instead seem to succeed at the task by decreasing the dispersion of the ISI distribution and increasing the occurrence of the modal ISI.
  • Monkeys mediate response through proprioceptive feedback:
    • Cervical spinal cord sectioning decreases the fidelity of control.
    • When contralateral C5-7 ventral roots were sectioned, PTN responsive to passive arm movements could not be statistically controlled.
    • Thus, monkeys operantly control precentral neurons through peripheral movements, perhaps even small and isometric contractions.
  • Excellent paper. Insightful conclusions.


[0] Wyler AR, Lange SC, Neafsey EJ, Robbins CA, Operant control of precentral neurons: control of modal interspike intervals.Brain Res 190:1, 29-38 (1980 May 19)

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ref: Fetz-1992 tags: Fetz 1992 Motor control M1 PV date: 01-06-2012 18:13 gmt revision:1 [0] [head]

bibtex: Fetz-1992 Are movement parameters recognizably coded in the activity of single neurons

  • Fetz seems to think that many of the reported correlations or specializations, whether in terms of latency or tuning, are largely a result of observer bias (e.g. to ignore non-obviously tuned cells), and that both simple and complex tuning to motor parameters can be found throughout the motor and premotor cortices.
    • Plus, evidence seems to point to the fact that most things happen simultaneously across multiple areas.
  • Shows that a neural-network model of M1 has complicated and interesting tuning within the hidden network, which he thinks is consistent with the observations.
  • Nice: "This suggests that the search for explicit coding may be diverting us from understanding distributed neural mechanisms that operate without literal representations. "

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ref: notes-0 tags: motor control BMI M1 date: 01-06-2012 03:11 gmt revision:13 [12] [11] [10] [9] [8] [7] [head]

with: {277}

  • Correlations have been described between neuronal activity and the static and dynamic forces and torques generated across single joints
  • or by the whole arm
  • or by precision pinch [14,15,16]
  • or there are strong correlations to muscle activity [17,18,19,20,21,22,23,24,25]
  • or there is strong correlations to kinematic parameters
  • these kinematic parameters are dependent on location in the external workspace [10][28,29]
  • kinematic tuning can be subserved by training! [30]
  • distance to target representation [31]


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ref: -2008 tags: OCZ NIA teardown autopsy BMI BCI date: 01-06-2012 03:09 gmt revision:19 [18] [17] [16] [15] [14] [13] [head]

Recently we bought a OCZ NIA device for our lab. Having designed similar hardware myself, I simply *had to* take the thing apart to inspect it, as others have done -- see Joe Pit's teardown (with schematic!!). Of course, I graciously let the others try it for a few hours (it doesn't work all that well) before taking the anodized, extruded, surface- ground aluminum case apart. Below is the top side of the 4-layer circuit board inside the case, as well as a key to indicate the function of the labeled devices. (some of the labels are hard to read due to the clutter of the silkscreen on the board; sorry).

  • A - Input connector. Center channel is isolated ground; outside two channels are the signal. They had to make this custom so people couldn't plug it into other (possibly dangerous) stuff.
  • B - Input current limiting resistors, in series with signal, 4.02K
  • C - Dual capacitor from input channels to shared ground (I think; the cap has 4 contacts, 2 at the end, 2 in the middle; I assume they use this package to get very accurately matched capacitance so as not to hurt the CMRR of the instrumentation amplifier).
  • D - Gain-setting resistor, 1.00K. Sets the instrumentation amplifier gain to 50 (I think).
    • I do not know what devices were intended for the 1206 footprints above and below this resistor...
  • E - Instrumentation amplifier, Analog Devices logo, AD8220 by my guess, A-grade. Measures the difference in voltage between the two input channels (left and right electrodes on the headband).
  • F - 47 ohm resistors & capacitors to filter the power supply to the instrumentation amplifier.
  • H - Opamp, Texas Instruments OPA348A. Looks like it is used as feedback to the instrumentation amplifier reference pin to effect highpass operation (?).
  • I - Quad opamp, TI OPA4348A. Used to filter the signal; I did not go through the filter topology, but they might have copied it off the AD8220 datasheet ;)
  • J - Stereo ADC, Texas Instruments (Burr-Brown logo, TI bought BB) PCM1803A. Only one channel is used. 24 bits, 96khz max sampling rate; device in master mode (Mode1 = 0V, Mode0 = 3.3v); Fs = SCLK/512 -> sampling rate = 3.90625 KHz.
  • K - Three channel digital isolator, Analog Devices ADUM1300. Transmits the ADC's DOUT, BCK, and LRCLK signals to the USB (non-isolated) side.
  • L - Two-channel optical (?) isolator; unknown type; used to drive the ADC's SCLK and some other signal ?
    • from Joe Pits: "Yeah, optical isolator with logic gates for high speed I guess (HCPL2631S). I'm also not sure what the second signal does, it goes to U4 (JSR marking). I suspect it could be a switch which adds C14 + R17 in the feedback loop of U2C (see the schematic). But I don't know what the reason for this is."
  • M - Isolated supply daughterboard, Texas Instruments logo, very simple design: driver is 2 BJTs (which get hot!) in push-pull topology; bases are driven by windings on the toroidal transformer; transformer center tap seems to go to USB VCC. Output is +-5V.
  • N - +3.9V, +3.3, and -3.9V power supply circuitry. I cannot identify the SOT-23-5's and SC-70's here.
  • O - PIC18F2455, with USB 2.0 (obviously!) SOIC-28 package.
    • device comes up as (on my Linux box, Debian Lenny, kernel 2.6.24):
      • usb 4-1: new full speed USB device using uhci_hcd and address 8
      • hiddev96hidraw1: USB HID v1.10 Device [Brain Actuated Technologies Neural Impulse Actuator Prototype 1.0] on usb-0000:00:1a.1-1
    • I'll put up a usbmon trace later, maybe.
  • P - Transistors for driving the tricolor LEDS on the bottom of the board.
  • Q - 16.0000 MHz crystal. Needed for correct USB timing; clocks the PIC at 48Mhz.
  • R - USB type B connector. Note the ferrites to the left. (I though they were fuses, but I accidentally shorted Vdd to ground while probing the programming connector, and these let out a little smoke rather than blowing completely. Had they been fuses, they would be open circuit now. This is consistent with Joe Pit's analysis.)
  • S - 74HCT595A 8-bit shift registers, to convert the serial data into parallel data for the PIC to read in. 3 devices = 24 bits in total.
    • Note that the 74HCT595A has a output enable, which permits the PIC to read the 3 bytes of the sample sequentially. Otherwise, as Stefan Jung (via the openeeg-list) points out, the PIC would not have enough data pins (28 pins vs. 24 bits)!
  • T - 74HCT393, Texas Instruments logo, Dual 4-bit binary ripple counter. Used to drive the ADC with a 2Mhz clock, which puts the sampling rate at (as before) 3.90625 KHz.
  • U - Programming connector. That's right, a programming connector! Looks to be the same as a PIC ICSP connector (pointed out on hack a day)
    • So far as I can tell:
      • Pin 1 = +5V, PIC pin 1, (through 100 ohm resistor), Vpp (?)
      • Pin 2 = PIC pin 20 , Vdd
      • Pin 3 = PIC pin 19 , Vss
      • Pin 4 = PIC pin 28 (through 100 ohm resistor), PGD
      • Pin 5 = PIC pin 27 (through 100 ohm resistor), PGC
    • I do not know if the device can be reprogrammed, though it looks that way.
    • from here - bootloader (to address 0x07ff) can be read, but everything above that is read-protected.
Bottom of board, showing the (very bright!) tricolor LEDs


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ref: Towe-2007.05 tags: RF recording passive backscatter variactors date: 01-06-2012 02:56 gmt revision:3 [2] [1] [0] [head]

IEEE-4227238 (pdf) Passive Backscatter Biotelemetry for Neural Interfacing

  • ahaha. Someone else had the same idea, about at the same time. And they got it to work!

IEEE-5993487 (pdf) A Fully Passive Wireless Microsystem for Recording of Neuropotentials Using RF Backscattering Methods

  • Still not that sensitive -- about an order of magnitude too coarse.
  • Also, no multiplexing.
  • But: there is room, I think this technology has potential.
  • range only 1.5cm.
  • suggest performance can be improved by increasing the nonlinearity of the variactors.
  • Other papers by the author feature ultrasound-powered microstimulation. He's clearly into alternative approaches.


Towe, B.C. Neural Engineering, 2007. CNE '07. 3rd International IEEE/EMBS Conference on 144 -147 (2007)

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ref: tlh24-2011 tags: motor learning models BMI date: 01-06-2012 00:19 gmt revision:1 [0] [head]

Experiment: you have a key. You want that key to learn to control a BMI, but you do not want the BMI to learn how the key does things, as

  1. That is not applicable for when you don't have training data - amputees, parapalegics.
  2. That does not tell much about motor learning, which is what we are interested in.

Given this, I propose a very simple groupweight: one axis is controlled by the summed action of a certain population of neurons, the other by a second, disjoint, population; a third population serves as control. The task of the key is to figure out what does what: how does the firing of a given unit translate to movement (forward model). Then the task during actual behavior is to invert this: given movement end, what sequence of firings should be generated? I assume, for now, that the brain has inbuilt mechanisms for inverting models (not that it isn't incredibly interesting -- and I'll venture a guess that it's related to replay, perhaps backwards replay of events). This leaves us with the task of inferring the tool-model from behavior, a task that can be done now with our modern (though here-mentioned quite simple) machine learning algorithms. Specifically, it can be done through supervised learning: we know the input (neural firing rates) and the output (cursor motion), and need to learn the transform between them. I can think of many ways of doing this on a computer:

  1. Linear regression -- This is obvious given the problem statement and knowledge that the model is inherently linear and separable (no multiplication factors between the input vectors). n matlab, you'd just do mldivide (backslash opeartor) -- but but! this requires storing all behavior to date. Does the brain do this? I doubt it, but this model, for a linear BMI, is optimal. (You could extend it to be Bayesian if you want confidence intervals -- but this won't make it faster).
  2. Gradient descent -- During online performance, you (or the brain) adjusts the estimates of the weights per neuron to minimize error between observed behavior and estimated behavior (the estimated behavior would constitute a forward model..) This is just LMS; it works, but has a exponential convergence and may get stuck in local minima. This model will make predictions on which neurons change relevance in the behavior (more needed for acquiring reward) based on continuous-time updates.
  3. Batched Gradient descent -- Hypothetically, one could bolster the learning rate by running batches of data multiple times through a gradient descent algorithm. The brain very well could offline (sleep), and we can observe this. Such a mechanism would improve performance after sleep, which has been observed behaviorally in people (and primates?).
  4. Gated Gradient Descent -- This is halfway between reinforcement learning and gradient descent. Basically, the brain only updates weights when something of motivational / sensory salience occurs, e.g. juice reward. It differs from raw reinforcement learning in that there is still multiplication between sensory and motor data + subsequent derivative.
  5. Reinforcement learning -- Neurons are 'rewarded' at the instant juice is delivered; they adjust their behavior based on behavioral context (a target), which presumably (given how long we train our keys), is present in the brain at the same time the cursor enters the target. Sensory data and model-building are largely absent.

{i need to think more about model-building, model inversion, and songbird learning?}

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ref: Velliste-2008.06 tags: Schwartz 2008 Velliste BMI feeding population vector date: 01-06-2012 00:19 gmt revision:1 [0] [head]

PMID-18509337[0] Cortical control of a prosthetic arm for self-feeding

  • Idea: move BMI into robotic control.
  • population vector control, which has been shown to be inferior to the Wiener filter.
  • 112 units for control in one monkey. 2 monkeys used.
  • 4D control -- x, y, z, gripper.
  • 1064 trials over 13 days, average success rate of 78%
  • Gripper opened as the arm returned to mouth. Works b/c marshmallows are sticky.


[0] Velliste M, Perel S, Spalding MC, Whitford AS, Schwartz AB, Cortical control of a prosthetic arm for self-feeding.Nature 453:7198, 1098-101 (2008 Jun 19)

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ref: Nicolelis-1993 tags: neurons somatosensory nicolelis rats thalamus date: 01-03-2012 23:30 gmt revision:2 [1] [0] [head]

from the Scientific American:

  • blocking (single?) neuron activity in S1 cortex affects the responses of VPM neurons in the thalamus - indicating that descending feedback signals in the cortex to the VPM could have a major role in modulating the ascending information.
  • if you implant a cuff electrode aroung the trigeminal nerve, the evoked responses in S1 and VPM are dependent on the behavioral state of the animal (of course!). this effect is so pronounced that, when the rats were not 'paying attention', only the first stimulus of a series evoked a response; when the rat was whisking, stimulation was faithfully reported.

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ref: Evarts-1969.05 tags: Evarts pyramidal tract motor control M1 tuning date: 01-03-2012 23:08 gmt revision:2 [1] [0] [head]

PMID-4977837[0] Activity of Pyramidal Tract neurons during postural fixation

  • Force was thus dissociated from displacement, and it was possible to determine whether PTN discharges were related to position or force.
  • for the majority of PTNs discharge frequency was related to to the magnitude and rate of change of force rather than to the joint position or the speed of joint movement (same as the MUA in the Kinarm data!!)
  • task was simple: just try to avoid joint movement.
  • in comparison to [1] where PTN were related to force under joint displacement, this task shows they are still related to force even when the joint angle is fixed.
  • used sharpened tungsten electrodes to record 102 pyramidal tract neurons.
  • monkeys were trained to do the tasks in their home cages (obviously weren't recorded there - need to be headposted)
  • I'm not sure how he determined if it was or was not a pyramidal tract neuron.


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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: 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 ) is the Mann-Whitney test statistic, which non-parametrically estimates the difference between two distributions.
  • δf(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 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: MolinaLuna-2007.03 tags: ICMS microstimulation cortical thin-film electrodes histology MEA date: 01-03-2012 22:54 gmt revision:2 [1] [0] [head]

PMID-17178423[0] Cortical stimulation mapping using epidurally implanted thin-film microelectrode arrays.

  • they claim that thin-film electrodes are better than microelectrode arrays, as they show less evidence of cortical damage.
    • thin-film electrodes show higher reproducability
    • more accurate spatial arrangement.
  • epidural stimulation (they were implanted between the dura and skull)


[0] Molina-Luna K, Buitrago MM, Hertler B, Schubring M, Haiss F, Nisch W, Schulz JB, Luft AR, Cortical stimulation mapping using epidurally implanted thin-film microelectrode arrays.J Neurosci Methods 161:1, 118-25 (2007 Mar 30)

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

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

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

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

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

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


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

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ref: Dabrowski-2003.1 tags: ASIC neural recording poland neuroplat pseudoresistor date: 01-03-2012 15:24 gmt revision:4 [3] [2] [1] [0] [head]

IEEE-1351853 (pdf) Development of integrated circuits for readout of microelectrode arrays to image neuronal activity in live retinal tissue

  • Use miller effect to increas capacitance for HPF.
  • resistors are long channel PMOS 3um / 500um, biased in linear region @ 0V.
    • Transistors must be in linear region: implement gate following of input signal. By varying this gate voltage, can change the filter characteristics.
  • Amplifier looks rather clever.
  • 7uV RMS input-referred noise.


Dabrowski, W. and Grybos, P. and Hottowy, P. and Skoczen, A. and Swientek, K. and Bezayiff, N. and Grillo, A.A. and Kachiguine, S. and Litke, A.M. and Sher, A. Nuclear Science Symposium Conference Record, 2003 IEEE 2 956 - 960 Vol.2 (2003)

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ref: neuro-2005 tags: NRSA background BMI tool use date: 01-03-2012 15:21 gmt revision:2 [1] [0] [head]

  • tool use:
    • [0]
    • [1] varying neural responses following tool acquisition
  • BMI
    • [2] simultaneous prediction of 4 variables
  • spike sorting
    • [3] donoghue
    • [4] LFP
    • [5] MUA
    • [6,7] - 1980!!
    • [8] STN bmi (nahh)
    • [9] Shenoy, eye movement better, 6.5 bits/sec
    • [10] PF
    • [11] in rats, in the cinglate, still they didn't get the point.
    • [12] Fetz stimulation


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ref: Lim-2009.09 tags: auditory midbrain implant deaf cochlea stimulation inferior colliculus date: 01-03-2012 06:55 gmt revision:2 [1] [0] [head]

PMID-19762428[0] Auditory midbrain implant: a review.

  • Inferior to a cochlear implant -- subjects, at the best, could understand speech only with lip-reading cues.
  • But! It's safe, and offers some degree of perception.
  • Also see: PMID-21157353[1]
    • Neurofibramatosis type 2 can also lead to cochlear deafness.
    • Implanted in the dorsal and ventral cochlear nuclei in the lateral recess of the IVth ventricle of the brain stem.
    • EABRs (evoked auditory brain stem responses); even though these were associated with electrodes in the right place, they could not be used for device fitting (?)


[0] Lim HH, Lenarz M, Lenarz T, Auditory midbrain implant: a review.Trends Amplif 13:3, 149-80 (2009 Sep)
[1] O'Driscoll M, El-Deredy W, Ramsden RT, Brain stem responses evoked by stimulation of the mature cochlear nucleus with an auditory brain stem implant.Ear Hear 32:3, 286-99 (2011 May-Jun)

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ref: Butovas-2007.04 tags: Butovas Schwarts ICMS stimulation rat barrel cortex date: 01-03-2012 06:55 gmt revision:2 [1] [0] [head]

PMID-17419757[0] Detection psychophysics of intracortical microstimulation in rat primary somatosensory cortex.

  • headposted rats, ICMS to barrel cortex
  • single pulse threshold = 2 nC, around the threshold for evocation of short-latency action potentials near an electrode.
  • one pulse saturated at 80% correct.
  • multiple pulses had a higher rate, though this saturated at 15 pulses.
  • double pulse optimal in terms of power / discrimination.


[0] Butovas S, Schwarz C, Detection psychophysics of intracortical microstimulation in rat primary somatosensory cortex.Eur J Neurosci 25:7, 2161-9 (2007 Apr)

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ref: Blum-2004.01 tags: microstimulator MEA Georgia Blum integrated circuit date: 01-03-2012 06:53 gmt revision:3 [2] [1] [0] [head]

PMID-17271195[0] Models of stimulation artifacts applied to integrated circuit design.

  • for MEAs.
  • Idea: develop a model of the stimulation artifact so they can optimize removal in SPICE.
  • reference documents that say that biphasic stimulation + active artifact suppression (by discharging the electrodes after stimulation, [1]) are acknowledged means of reducing stimulus artifact.
  • artifact appears to be 1ms saturating, 6ms non-saturating pulse.
  • a little light on details.


[0] Blum R, Ross J, Das S, Brown E, Deweerth S, Models of stimulation artifacts applied to integrated circuit design.Conf Proc IEEE Eng Med Biol Soc 6no Issue 4075-8 (2004)
[1] Jimbo Y, Kasai N, Torimitsu K, Tateno T, Robinson HP, A system for MEA-based multisite stimulation.IEEE Trans Biomed Eng 50:2, 241-8 (2003 Feb)

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

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

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


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ref: Moran-1999.11 tags: electrophysiology motor cortex Schwartz Moran M1 tuning date: 01-03-2012 03:36 gmt revision:2 [1] [0] [head]

PMID-10561437[0] Motor cortical representation of speed and direction during reaching

  • velocity is represented in the motor cortex.
  • they developed an equation relating firing rate to the position and velocity.
  • EMG direction had significantly different tuning from the cortical activity
    • the effect of speed on EMG was also different.
  • used single-electrode recording - 1,066 cells!!
  • introduce the square-root transformation of the firing rate (from Ashe and Georgopolous 1994)


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ref: Fu-1993.11 tags: electrophysiology Ebner premotor motor tuning M1 date: 01-03-2012 03:34 gmt revision:1 [0] [head]

PMID-8294972 Neuronal specification of direction and distance during reaching movements in the superior precentral premotor area and primary motor cortex of monkeys. 1993

  • trained monkey to do center-out task, 48 targets (8 angles, 6 distances).
  • single-electrode recording of 197 neurons in the primary motor and secondary motor / premotor (in the superior precentral sulcus).
  • cells were mostly tuned to direction, and less to distance, in both the premovement and movement periods. distance tuning was much stronger in the movement period.
    • tuning was measure by average firing rate for the premovement, movement, and total periods.
  • long, very detailed!

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

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

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


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

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ref: 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: Rolston-2009.01 tags: ICMS artifacts stimulation Rolston Potter recording BMI date: 01-03-2012 02:38 gmt revision:3 [2] [1] [0] [head]

PMID-19668698[0] A low-cost multielectrode system for data acquisition enabling real-time closed-loop processing with rapid recovery from stimulation artifacts

  • Well written, well tested, but fundamentally simple system - only two poles active high-pass, one pole low-pass.
  • With TBSI headstages the stimulation artifact is brief - figure 8 shows < 4ms.
  • Includes NeuroWriter software, generously open-sourced (but alas windows only - C#).


[0] Rolston JD, Gross RE, Potter SM, A low-cost multielectrode system for data acquisition enabling real-time closed-loop processing with rapid recovery from stimulation artifacts.Front Neuroengineering 2no Issue 12 (2009)

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ref: Fontani-2007.12 tags: mental training skilled motor control date: 01-03-2012 02:33 gmt revision:2 [1] [0] [head]

PMID-18229536[0] Effect of mental imagery on the development of skilled motor actions.

  • with trained subjects (performing something called Ura-Shuto-Uchi (Japanese? but the researchers are Italian)) showed a decrease in reaction time and EMG activity, as well as a increase in movement speed, muscle strength, power, and work. These results did not apply to untrained individuals. EEG also apparently changed vs. the untrained condition.


[0] Fontani G, Migliorini S, Benocci R, Facchini A, Casini M, Corradeschi F, Effect of mental imagery on the development of skilled motor actions.Percept Mot Skills 105:3 Pt 1, 803-26 (2007 Dec)

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ref: 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: Grutzendler-2011.09 tags: two-photon imaging in-vivo neurons recording dendrites spines date: 01-03-2012 01:02 gmt revision:3 [2] [1] [0] [head]

PMID-21880826[0] http://cshprotocols.cshlp.org/content/2011/9/pdb.prot065474.full?rss=1

  • Excellent source of information and references. Go CSH!
  • Possible to image up to 400um deep. PMID-12490949[1]
  • People have used TPLSM imaging for years in mice. PMID-19946265[2]


[0] Grutzendler J, Yang G, Pan F, Parkhurst CN, Gan WB, Transcranial two-photon imaging of the living mouse brain.Cold Spring Harb Protoc 2011:9, no Pages (2011 Sep 1)
[1] Grutzendler J, Kasthuri N, Gan WB, Long-term dendritic spine stability in the adult cortex.Nature 420:6917, 812-6 (2002 Dec 19-26)
[2] Yang G, Pan F, Gan WB, Stably maintained dendritic spines are associated with lifelong memories.Nature 462:7275, 920-4 (2009 Dec 17)

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ref: Lemon-1976.1 tags: Lemon motor recording afferent input date: 01-03-2012 01:01 gmt revision:1 [0] [head]

PMID-11491[0] Afferent input to movement-related precentral neurones in conscious monkeys.

  • Trained monkeys to make both a stereotyped movement and respond passively and calmly to external stimulation.
  • Most cells recorded responded to joint velocity; none to joint position.
  • A smaller subset responded to muscle palpitation
  • Cells were tuned to similar things as their neighbors, though sometimes they responded to markedly different stimuli. Consistent with Wyler.


[0] Lemon RN, Porter R, Afferent input to movement-related precentral neurones in conscious monkeys.Proc R Soc Lond B Biol Sci 194:1116, 313-39 (1976 Oct 29)

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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: YaoHong-2009.1 tags: wireless transmitter modulator QPSK date: 01-03-2012 00:56 gmt revision:2 [1] [0] [head]

IEEE-5256305 (pdf) A 200-pJ/b MUX-Based RF Transmitter for Implantable Multichannel Neural Recording

  • 400Mhz band
  • 17Mbps
  • 0.18um CMOS process, 1.2-1.8V, 2.9mA, -8dbM output power.
  • 0.2 nJ/bit
  • 1.2mm^2
  • no receiver, though a COTS one could probably be purchased.
  • O-QPSK (offset quadrature phase shift keying)
  • VCO operates at 2x the output frequency.
  • No IF.
  • PSK > FSK.
  • Measured error vector magnitude (EVM), which is approx 8% over the data rate.
    • This due to phase noise in the LO & phase mismatch.
    • Typical O-QPSK requires 23% EVM for a BER of 10^-4
  • Almost as good as UWB.


Yao-Hong Liu and Cheng-Lung Li and Tsung-Hsien Lin A 200-pJ/b MUX-Based RF Transmitter for Implantable Multichannel Neural Recording Microwave Theory and Techniques, IEEE Transactions on 57 10 2533 -2541 (2009)

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ref: -0 tags: bookmark Cory Doctorow EFF SOPA internet freedom date: 01-01-2012 21:51 gmt revision:0 [head]

The Coming War on General Computation "M.P.s and Congressmen and so on are elected to represent districts and people, not disciplines and issues. We don't have a Member of Parliament for biochemistry, and we don't have a Senator from the great state of urban planning, and we don't have an M.E.P. from child welfare. "

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

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

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


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ref: Nicolelis-1998.11 tags: spatiotemporal spiking nicolelis somatosensory tactile S1 3b microwire array rate temporal coding code date: 12-28-2011 20:42 gmt revision:3 [2] [1] [0] [head]

PMID-10196571[0] Simultaneous encoding of tactile information by three primate cortical areas

  • owl monkeys.
  • used microwires arrays to decode the location of tactile stimuli; location was encoded through te population, not within single units.
  • areas 3b, S1 & S2.
  • used LVQ (learning vector quantization) backprop, LDA to predict/ classify touch trials; all yielded about the same ~60% accuracy. Chance level 33%.
  • Interesting: "the spatiotemporal character of neuronal responses in the SII cortex was shown to contain the requisite information for the encoding of stimulus location using temporally patterned spike sequences, whereas the simultaneously recorded neuronal responses in areas 3b and 2 contained the requisite information for rate coding."
    • They support this result by varying bin widths and looking at the % of correctly classivied trials. in SII, increasing bin width decreases (slightly but significantly) the prediction accuracy.


[0] Nicolelis MA, Ghazanfar AA, Stambaugh CR, Oliveira LM, Laubach M, Chapin JK, Nelson RJ, Kaas JH, Simultaneous encoding of tactile information by three primate cortical areas.Nat Neurosci 1:7, 621-30 (1998 Nov)

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ref: -0 tags: Georgoplous todorov M1 controversy square root bias PV date: 12-22-2011 22:52 gmt revision:2 [1] [0] [head]

PMID-11017158 One motor cortex, two different views

  • ref {950}, {952}, {953}
  • Georgopoulos re-analyzed their data without squareroot transformation and without smothing -- using only binned rates -- and found that it did not substantially change the porportions of tuned cells
  • In return, Todorov {955} responds that classifying cells based on maximal R^2 is stupid -- many cells lie on the decision boundaries in this manifold.

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ref: -0 tags: todorov R2 M1 PV tuning bias decision boundaries controversy date: 12-22-2011 22:52 gmt revision:1 [0] [head]

PMID-11017160 Reply to One motor cortex, two different views

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ref: -0 tags: Scott M1 motor control pathlets filter EMG date: 12-22-2011 22:52 gmt revision:1 [0] [head]

PMID-19923243 Complex Spatiotemporal Tuning in Human Upper-Limb Muscles

  • Original idea: M1 neurons encode 'pathlets', sophisticated high-level movement trajectories, possibly through the action of both the musculoskeletal system and spinal cord circuitry.
  • Showed that muscle pathlets can be extracted from EMG data, relkiably and between patients, implying that M1 reflects 'filter-like' properties of the body, and not high level representations.

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ref: -0 tags: todorov PV M1 controversy Scott date: 12-22-2011 22:22 gmt revision:1 [0] [head]

PMID-10725914 Population vectors and motor cortex: neural coding or epiphenomenon?

  • Basic friendly editorial of {950}.
  • On the PV method: "These correlations have been interpreted as suggesting that the motor cortex controls higher-level features of hand movements, rather than the lower-level features related to the individual joints and muscles that bring about those movements"
  • Implies that conversion of the relatively abstract representation to the concrete muscle activations would be done by the spinal cord.
    • This in turn implies that the spinal cord is capable of organizatonal-level learning, or that gross properties are genetically / developmentally encoded.
  • On Schwartz's drawing experiments: [The variable latency for the correlation of the PV tuning and arm motion] was interpreted that motor cortex is involved in controlling movements with high curvature, but not relatively straight movements.
  • Nice: "Engineers have to understand the plant before they can figure out how to control it. Why should it be any different when examining biological control?"

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ref: -0 tags: Moran Schwartz Todorov controversy PV M1 motor control date: 12-22-2011 22:04 gmt revision:0 [head]

PMID-11017157 One motor cortex, two different views.

  • Commentary on {950}
  • Refutes Todorov's stiff -muscle perturbation analysis, saying that it grossly misapproximates what the monkey is actually doing (drawing on a touchscreen vertical in front of it), as the model of the arm in this case would be held stiffly in front of the monkey, rather than realistically falling to the animal's side.
  • They also claim that any acceleration term would cause the PV tuning to lead with higher curvature, which is not what they saw (?)

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ref: -0 tags: Todorov motor control models 2000 date: 12-22-2011 21:18 gmt revision:3 [2] [1] [0] [head]

PMID-10725930 Direct cortical control of muscle activation in voluntary arm movements: a model.

  • Argues that the observed high-level control of parameters (movement direction) is inconsistent with demonstrated low-level control (control of individual muscles / muscle groups, as revealed by STA [5] or force production [3]), but this inconsistency is false: the principle of low level control is correct, and high level control appears due to properties of the musculoskeletal system.
  • "Yet the same cells that encode hand velocity in movement tasks can also encode the forces exerted against external objects in both movement and isometric tasks [9,10].
  • The following other correlations have been observed:
    • arm position [11]
    • acceleration [12]
    • movement preparation [13]
    • target position [14]
    • distance to target [15]
    • overall trajectory [16]
    • muscle coactivation [17]
    • serial order [18]
    • visual target position [19]
    • joint configuration [20]
    • instantaneous movement curvature [7]
    • time from movement onset [15]
  • although these models can fit the data well, they leave a crucial question unanswered, namely, how such a mixed signal can be useful for generating motor behavior.
    • What? No! The diversity of voices gives rise to robust, dynamic computation. I think this is what Miguel has written about, will need to find a reference.
  • Anyway, all the motor parameters are related by the laws of physics -- the actual dimensionality of real reaches is relatively low.
  • His model: muscle activity simply reflects M1 PTN activity.
  • If you include real muscle parameters, a lot of the observed correlations make sense: muscle force depends not only on activation, but also on muscle length and rate of change of length.
  • In this scientific problem, the output (motor behavior) specified by the motor task is easily measured, and the input (M1 firing) must be explained.
    • Due to the many-to-one mapping, there is a large null-space of the inverse transform, so individual neurons cannot be predicted. Hence focus on population vector average.
  • Cosine tuning is the only activation pattern that minimizes neuromotor noise (derived in methods, Parseval's theorem)). Hence he uses force, velocity, and displacement tuning for his M1 cells.
  • Activity of M1 cells is constrained in endpoint space, hence depends only on behavioral parameters.
    • The muscles were "integrated out".
  • Using his equation, it is clear that for an isometric task, M1 activity is cosine tuned to force direction and magnitude -- x(t) is constant.
  • For hand kinematics in the physiological range with an experimentally measured inertia-to-damping ratio, the damping compensation signal dominates the acceleration signal.
    • Hence population x˙(t)
    • Muscle damping is asymmetric: predominant during shortening.
  • The population vector ... is equal not to the movement direction or velocity, but instead to the particular sum of position, velocity, acceleration, and force signals in eq. 1
  • PV reconstruction fails when movement and force direction are varied independently. [28]
  • Fig 4. Schwartz' drawing task -- {951} -- and shows how curvature, naturalistic velocity profiles, the resultant accelerations, and leading neuronal firing interact to distort the decoded PV.
    • Explains why, when assuming PV tuning, there seems to be variable M1-to-movement delay. At high curvature PV tuning can apprently lag movement. Impossible!
  • Fig 5 reproduces [21]
    • Mean firing rate (mfr, used to derive the poisson process spike times) and r^2 based classification remarkably different -- smoothing + square root biases toward finding direction-tuned cells.
    • Plus, as P, V, and A are all linearly related, a sum of the 3 is closer to D than any of the three.
    • "Such biases raise the important question of how one can determine what an individual neuron controls"
  • PV reversals occur when the force/acceleration term exceeds the velocity scaling term -- which is 'equivalent' to the triphasic burst pattern observed in EMG. Ergo monkeys should be trained to make faster movements.
  • The structure of your model -- for example firingrate=b 0+b xX+b yY+b mM biases analysis for direction, not magnitude; correct model is firingrate=b 0+b xmXM+b ymYM -- multiplicative.
  • "Most of these puzzling phenomena arise from the feedforward control of muscle viscoelasticity."
  • Implicit assumption is that for the simple, overtrained, unperturbed movements typically studied, feedforward neural control is quite accurate. When you get spinal reflexes involved things may change. Likewise for projections from the red nucleus.

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ref: -0 tags: Georgopoulos population vector arm motor control date: 12-20-2011 22:26 gmt revision:1 [0] [head]

PMID-3139485 Neural integration of movement: role of motor cortex in reaching.

  • Reviews his 2D and 3D population vector / cosine tuning results.
  • Isometric task in [13] varied as a sinusoidal function of load.
    • [1]3 Kalaska 1985 Area 4 and area 5: differences between the load direction-dependent discharge variability of cells during active postural fixation.
  • [14] suggests that separate motor cortical populations are concerned with the control of joint stiffness.
    • [14] Humphrey 1983 Seperate cortical systems for control of joint movement and joint stiffness: reciprocal activation and coactivation of antagonist muscles.
  • proximal muscles are controlled through C3-C4 propriospinal neurons, which receive input from corticospinal, rubrospinal, reticulospinal, and tectospinal tracts, and distribute axons to proximal motorneuron pools [25]
    • The propriospinal system seems to be selectively engaged during reaching movements [28].
    • There is corticspinal input on key inhibitory interneuron that mediates inhibition from afferent fibers to propriospinal neurons [29].
    • References in this from the cat.
  • This is similar to 'the sophisticated integration seen in the locomotor system' locomotive system.
  • From this, Georgopoulos supposes that the motor cortex is concerned with the specification of the direction of reaching in space.
  • He further supposes that this is enacted by individual motor cortical cells influence motoneuronal pools in a weighted fashion.
  • Looking back, I'm surprised at how clean his PV tuning plots are -- the neurons stop fiting when the monkey moves his arm in certain directions.

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ref: Hassell-2007.08 tags: microstimulator ICMS ASIC Hassel date: 12-20-2011 06:17 gmt revision:1 [0] [head]

IEEE-4352820 (pdf) Constant-Current Adjustable-Waveform Microstimulator for an Implantable Hybrid Neural Prosthesis

  • Focus on hybrid electro-chemical prosthesis: electrical release of glutamate. For "native output modality".
    • For use in neuronal culture, at least initially.
  • Talk about constant-current sources, typically current-mirrors. Want the following:
    • Linearity
    • High output impedance.
    • voltage compliance.
    • Are these things necessarily well motivated? constant power may be better. eh.
  • WAnt to cascode current output for greater output impedance.
  • They appear not to have completed the ASIC (at time of publication).


Hassell, T.J. and Jedlicka, S.S. and Rickus, J.L. and Irazoqui, P.P. Engineering in Medicine and Biology Society, 2007. EMBS 2007. 29th Annual International Conference of the IEEE 2436 -2439 (2007)

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ref: -0 tags: Georgopoulos 1988 population vector tuning date: 12-20-2011 01:13 gmt revision:1 [0] [head]

PMID-3411362[0] Primate motor cortex and free arm movements to visual targets in three-dimensional space. II. Coding of the direction of movement by a neuronal population.

  • This is the paper where they do predictions, and show that they can offline 'decode' 3D reaching movements.
    • Pretty spiffy 3D graphics, too.
  • Used three analyses to estimate variability of the population vector.
    • 1. Random sampling of the experimentally observed population (N= 475), using the mean discharge rate of each cell to each direction.
    • 2. Same cell population, but variability of discharge was drawn from a normal distro estimated from the mean and variance of the trial-to-trial recordings.
    • 3. Random sampling + trial-to-trial variability.
  • Plot 95% confidence interval over population size for the estimated direction; asymtopes at about 15%. Why not measured in steradians?
  • Figure 4 looks to have good SNR, and they look to be dataheads.
  • Use a bunch of different weighting functions to calculate the population vector; no numerical optimization?
    • best one basically looks like normalized, mean-removed firing rate.


[0] Georgopoulos AP, Kettner RE, Schwartz AB, Primate motor cortex and free arm movements to visual targets in three-dimensional space. II. Coding of the direction of movement by a neuronal population.J Neurosci 8:8, 2928-37 (1988 Aug)

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ref: -0 tags: Georgopoulos 1988 M1 population vector tuning 3D single unit date: 12-20-2011 00:58 gmt revision:2 [1] [0] [head]

PMID-3411363[0] Primate motor cortex and free arm movements to visual targets in three-dimensional space. III. Positional gradients and population coding of movement direction from various movement origins.

  • In comparison to the first experiment, where they showed that movement direction was encoded by single units within M1, here they varied the starting position of the movements.
  • tonic discharge of many cells varied in and orderly fashion with the position at which the hand was actively maintained in space.
  • however, cell activity changes were the same independent of movement onset and dependent on movement direction.
    • similar but not that similar -- vary based on tonic firing rate. See figure 9.


[0] Kettner RE, Schwartz AB, Georgopoulos AP, Primate motor cortex and free arm movements to visual targets in three-dimensional space. III. Positional gradients and population coding of movement direction from various movement origins.J Neurosci 8:8, 2938-47 (1988 Aug)

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ref: Schwartz-1988.08 tags: Georgopoulos 1988 motor coding cortex population vector date: 12-20-2011 00:49 gmt revision:3 [2] [1] [0] [head]

PMID-3411361[0] Primate motor cortex and free arm movements to visual targets in three-dimensional space. I. Relations between single cell discharge and direction of movement.

  • 475/568 (83%) of cells varied in an orderly fashion with movement -- tuned to a movement direction.
    • As before, binned the firing based on movement direction.
  • generalize 2-D results [1][2]
  • Totally awesome tracking system: a spark gap was attached to the monkey's wrist and was discharged every 20ms. The sonic signal was picked up by at least 3 of the 8 ultrasonic recievers placed at the corners of the workspace and the xyz coordinates were calculated from the sonic delays using a microprocessor-based system.
  • monkey(s) had to press lighted buttons (arcade buttons) within this workspace.
  • otherwise same materials / methods as before.
  • every effort was made to isolate initially negative-going action potentials, and indication that the neuron was less likely to be damaged.
    • fiber spikes are initially positive. Cite Mountcastle et al 1969.
  • EMG signals gained 3000 and bandpassed 100-500Hz. rather narrow, but normal I guess.
  • Neural data recorded as interspike intervals.
  • vectoral dot-product tuning of cells, with the coeficients set by multiple linear regression.
    • This is equivalent to cosine tuning.
  • rather complicated CUSUM for determining onset of activity - including inhibition.
  • as in the earlier study, 60% of cells were tuned in the reaction time, and 85% within the movement time.
  • EMG activity looks like it can be described with cosine tuning as well.
  • 3D tuning directed over the whole space.
  • Residuals of firing rates measured with respect to the tuning functions; residuals were mean zero and approximately the same spread, and were distributed equally over the 3D space.
  • movement latency about 300ms. pretty quick reaction time?
  • Got some pretty awesome graphics for 1986 :)
  • The discharge rate of motor cortical cells varies with the magnitude of force and that cells with higher thresholds are recruited at progressively higher forces (Hepp-Reymond et al 1978).
  • Murphy et al 1982 found that ICMS to M1 caused rotation about single joints, which is inconsistent with cosine tuning (would require complex tuning, or tuning to joints).
  • They argue that cosine tuning refects transformatino by the propriospinal system, which engages patterns of muscle activity.
    • Most PTNs can influence several motoneuron pools in the spinal cord. (Fetz and Finocchio 1975, Fetz and Cheney 1978, 1980 ... Lemon 1986, Cheney and Fetz 1985)
    • Suggest that PTNs related to the weighted combinations of muscles.


[0] Schwartz AB, Kettner RE, Georgopoulos AP, Primate motor cortex and free arm movements to visual targets in three-dimensional space. I. Relations between single cell discharge and direction of movement.J Neurosci 8:8, 2913-27 (1988 Aug)
[1] Georgopoulos AP, Kalaska JF, Caminiti R, Massey JT, On the relations between the direction of two-dimensional arm movements and cell discharge in primate motor cortex.J Neurosci 2:11, 1527-37 (1982 Nov)
[2] Thach WT, Correlation of neural discharge with pattern and force of muscular activity, joint position, and direction of intended next movement in motor cortex and cerebellum.J Neurophysiol 41:3, 654-76 (1978 May)

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ref: Georgopoulos-1982.11 tags: Georgopoulos 1982 motor tuning cortex M1 population vector date: 12-19-2011 23:52 gmt revision:1 [0] [head]

PMID-7143039 On the relations between the direction of two-dimensional arm movements and cell discharge in primate motor cortex.

  • eight directions 45deg intervals, 2D joystick, frictionless, LED tarkets in a blocked randomized experimental design.
    • MK made simultaneous saccades; saccade latency 150-170ms.
      • some motor cells responded to visual movement.
    • EMG activity began ~80ms before movement.
    • monkeys used both arms.
  • bell-shaped or cosine tuning in 75% of the cells.
    • This has also been described in the saccade system in the paramedian pontine reticular formation (Henn and Cohen 1976), the mesencelphatic reticular formation (Buttner eta la 1977) and the internal medullary lamina of the thalamus (Schlag and Schlag-Ney 1977)
  • cells tended to cluster by tuning in depth.
  • cells tended to respond to movement & small corrections to movement, but did not necessarily respond to non-task related movement. "Yet these same cells were frequently silent during other movements which also involved contraction of the same muscles [as used in the task]"
  • cell discharge was much stronger during active movements than during passive manipulations.
  • 64% of cells were activated before the earliest EMG changes; 87% before the onset of movement.
  • The famous one, where the population vector was formalized / conceived / validated.
  • most neurons begin firing ~ 100ms before movement begins.
  • useda PDP11/20 minicomputer to control the LEDs & data recording.
  • Thach 1978 -- approxmately equal proportions of motor cortical cells were related to muscle activity, hans position, and direction of intended movement Thach 1978) PMID-96223
  • single electrode Pt/Ir recording 2-3Mohm; recordings made for 6-7 hours.
  • cite georgopoulos 1983 -- they propose distributed population coding.
  • point out that the central problem -- upon which some progress has been made - is the translation between visual and motor coordinate frames.

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ref: Jackson-2006.11 tags: Fetz Andrew Jackson BMI motor learning microstimulation date: 12-16-2011 04:20 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

PMID-17057705 Long-term motor cortex plasticity induced by an electronic neural implant.

  • used an implanted neurochip.
  • record from site A in motor cortex (encodes movement A)
  • stimulate site B of motor cortex (encodes movement B)
  • after a few days of learning, stimulate A and generate mixure of AB then B-type movements.
  • changes only occurred when stimuli were delivered within 50ms of recorded spikes.
  • quantified with measurement of (to) radial/ulnar deviation and flexion/extension of the wrist.
  • stimulation in target (site B) was completely sub-threshold (40ua)
  • distance between recording and stimulation site did not matter.
  • they claim this is from Hebb's rule: if one neuron fires just before another (e.g. it contributes to the second's firing), then the connection between the two is strengthened. However, i originally thought this was because site A was controlling the betz cells in B, therefore for consistency A's map was modified to agree with its /function/.
  • repetitive high-frequency stimulation has been shown to expand movement representations in the motor cortex of rats (hmm.. interesting)
  • motor cortex is highly active in REM


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ref: Vijayakumar-2005.12 tags: schaal motor learning LWPL PLS partial least sqares date: 12-07-2011 04:09 gmt revision:1 [0] [head]

PMID-16212764[0] Incremental online learning in high dimensions


  • use locally linear models.
  • use a small number of regressions in selected dimensions of input space in the spirit of partial least squares regression. (like partial least-squares) hence, can operate in very high dimensions.
  • function to be approximated has locally low-dimensional structure, which holds for most real-world data.
  • use: the learning of of value functions, policies, and models for learning control in high-dimensional systems (like complex robots or humans).
  • important distinction between function-approximation learning:
    • methods that fit nonlinear functions globally, possibly using input space expansions.
      • gaussian process regression
      • support vector machine regression
        • problem: requires the right kernel choice & basis vector choice.
      • variational bayes for mixture models
        • represents the conditional joint expectation, which is expensive to update. (though this is factored).
      • each above were designed for data analysis, not incremental data. (biology is incremental).
    • methods that fit simple models locally and segment the input space automatically.
      • problem: the curse of dimensionality: they require an exponential number of models for accurate approximation.
        • this is not such a problem if the function is locally low-dim, as mentioned above.
  • projection regression (PR) works via decomposing multivariate regressions into a superposition of single-variate regressions along a few axes of input space.
    • projection pursuit regression is a well-known and useful example.
    • sigmoidal neural networks can be viewed as a method of projection regression.
  • they want to use factor analysis, which assumes that the observed data is generated from a low-dimensional distribution with a limited number of latent variables related to the output via a transformation matrix + noise. (PCA/ wiener filter)
    • problem: the factor analysis must represent all high-variance dimensions in the data, even if it is irrelevant for the output.
    • solution: use joint input and output space projection to avoid elimination of regression-important dimensions.
  • practical details: they use the LPWR algorithm to model the inverse dynamics of their 7DOF hydraulically-actuated gripper arm. That is, they applied random torques while recording the resulting accelerations, velocities, and angles, then fit a function to predict torques from these variables. The robot was compliant and not very well modeled with a rigid body model, though they tried this. The resulting LPWR generated model was 27 to 7, predicted torques. The control system uses this functional approximation to compute torques from desired trajectories, i think. The desired trajectories are generated using spline-smoothing ?? and the control system is adaptive in addition to the LPWR approximation being adaptive.
  • The core of the LPWR is partial-least squares regression / progression pursuit, coupled with gaussian kernels and a distance metric (just a matrix) learned via constrained gradient descent with cross-validation. The partial least squares (PLS) appears to be very popular in many fields, and there are an number of ways of computing it. Distance metric can expand without limit, and overlap freely. Local models are added based on MSE, i think, and model adding stops when the space is well covered.
  • I think this technique is very powerful - you separate the the function evaluation from the error minimization, to avoid the problem of ambiguous causes. Instead, when applying the LPWR to the robot, the torques cause the angles and accelerations -> but you invert this relationship: want to control the torques given trajectory. Of course, the whole function approximation is stationary in time - the p/v/a is sufficient to describe the state and the required torques. Does the brain work in the same way? do random things, observe consequences, work in consequence space and invert ?? e.g. i contracted my bicep and it caused my hand to move to the face; now I want my hand to move to my face again, what caused that? Need reverse memory... or something. Hmm. let's go back to conditional learning: if any animal does an action, and subsequently it is rewarded, it will do that action again. if this is conditional on a need, then that action will be performed only when needed.. when habitual, the action will be performed no matter what.. this is the nature of all animals, i think, and corresponds to rienforcement learning? but how? I suppose it's all about memory, and assigning credit where credit is due. the same problem is dealt with rienforcement learning. and yet things like motor learning seem so far out of this paradigm - they are goal-directed and minimize some sort of error. eh, not really. Clementine is operating on the conditioned response now - has little in the way of error. but gradually this will be built; with humans, it is built very quickly by reuse of existing modes. or conciousness.
  • back to the beginning: you dont have to regress into output space - you regress into sensory space, and do as much as possible in that sensory space for control. this is very powerful, and the ISO learning people (Porr et al) have effectively discovered this: you minimize in sensory space.
    • does this abrogate the need for backprop? we are continually causality-inverting machines; we are prredictive.


[0] Vijayakumar S, D'Souza A, Schaal S, Incremental online learning in high dimensions.Neural Comput 17:12, 2602-34 (2005 Dec)

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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: Wyler-1980.08 tags: Wyler Lange Robbins operant conditioning motor neurons contralateral bilateral specificity monkeys motor learning date: 12-06-2011 06:36 gmt revision:1 [0] [head]

PMID-6772272 Operant control of precentral neurons: bilateral single unit conditioning.

  • Used bilateral electrodes.
  • One neuron operantly conditioned, one not.
  • Switched the conditioned / controlled after performance was attained.
  • Evidence: neurons can be individually tuned, and operant control is not the result of spinal-level conditioning or change.
    • It is not the result of increased attention or increased muscle tone.
  • Simple question, simple paper.

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

PMID-6457106 Processing visual feedback information for movement control.

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

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ref: 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: Burnod-1982.11 tags: operant conditioning motor control learning Burnod Maton Calvet date: 11-26-2011 02:22 gmt revision:0 [head]

PMID-7140894 Short-term changes in cell activity of areas 4 and 5 during operant conditioning.

  • Seems that layers 4 and 5 act differently during operant conditioning of a simple task.
  • Layer 5 neurons become tuned to reward (?)
  • Can't get this article, have to go from the abstract.

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ref: Friston-2002.1 tags: neuroscience philosophy feedback top-down sensory integration inference date: 10-25-2011 23:24 gmt revision:0 [head]

PMID-12450490 Functional integration and inference in the brain

  • Extra-classical tuning: tuning is dependent on behavioral context (motor) or stimulus context (sensory). Author proposes that neuroimaging can be used to investigate it in humans.
  • "Information theory can, in principle, proceed using only forward connections. However, it turns out that this is only possible when processes generating sensory inputs are invertible and independent. Invertibility is precluded when the cause of a percept and the context in which it is engendered interact." -- proof? citations? Makes sense though.
  • Argues for the rather simplistic proof of backward connections via neuroimaging..

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ref: -0 tags: automatic programming synthesis loops examples date: 10-03-2011 22:28 gmt revision:1 [0] [head]

Open letter proposing some ideas on how to automate programming: simulate a human! Rather from a neuro background, and rather sketchy (as in vague, not as in the present slang usage).


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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: entropy life proteonomics transcription factors date: 07-08-2011 22:42 gmt revision:0 [head]

Reduction in Structural Disorder and Functional Complexity in the Thermal Adaptation of Prokaryotes -- read the article. These are my disordered, mesothermophylic notes.

  • Low and high temperature prokaryotes seem to have less protein disorder (as estimated by amino acid content, mostly, not actual structure) called IDR/IDP (intrinsically disordered regions or proteins).
  • IDR / IDPs seem essential in certain protein functions, such as transcription factors and ribosomal proteins.
  • hyperthermophyles have low genomic complexity and low protein disorder, possibly to combat the high disorder of their environment.
  • "life appears to be incompatible with less than about 1.5% disorder ". I would say that this is a rather conservative threshold.
  • transcription factors: "disorder is correlated with the number of genes they regulate, which suggests that their disorder is directly linked with functional complexity of the organism"
  • Transcription factor disorder is higher in psychrophiles (low temp) than hyperthermophiles, even though both show decreased genome size. Furthermore, disordered regions may confer temperature robustness at 40-50C as well as at low temperatures.
  • "...there is many evidence in the literature that structural disorder and complexity are correlated, both at the level of individual proteins, where IDP functions correlate with signaling and regulation, and whole genomes, where the frequency of disorder increases with increasing complexity of the organism [24], [25], [41], [52]. Thus, evolutionary changes (point mutations, deletions of regions, silencing of genes, etc…) that reduce disorder will tend to strip the organism of functions that increase its complexity, and leave functions that are required for its basic, non-regulated existence. In this sense, reduction in disorder is not a side-effect of selection for reduced complexity, rather the mechanism of this evolutionary drive."

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ref: -0 tags: Miguel pastor Julio Severo politics religion date: 01-31-2011 02:09 gmt revision:0 [head]

Email received January 30 2011 - I've tried to understand the story, but all i get a sense of is strange injured exaggerations, statements which try to draw ire.

The below-linked report is one of the most bizarre cases we have reported in quite a while.

A high-paid, prestigious professor at the Catholic Duke University, who was recently appointed to the Vatican's Academy of Sciences, mind you, is not only pro abortion and in favor of gay marriage, but he also is threatening to call the police on people who disagree with him on these issues -- specifically, one pastor (Julio Severo, a friend of ours) who works with troubled homosexuals desiring to quit the lifestyle, and another Christian who has spoken only in the mildest terms of this professor.

Now picture this if you will: Here we have a homeless Pastor, Julio Severo, who has been banned from his homeland for sincerely practicing his life work of helping homosexuals cope with unwanted desires. These are poor men who are terrified of contracting AIDS and dying. Some already have tested HIV positive. They come to Julio out of desperation for psychological and spiritual assistance, guidance from the Word of God. And now, for the crime of heeding God's call to help them, Pastor Severo is forced to leave his country or be jailed for the "crime" of helping homosexuals desirous of raising themselves out of a situation they deplore and fear. Because Brazil is in the hands of leftist elitists who have outlawed any public speech unfavorable to homosexuality.

Meanwhile, the desolate Pastor Severo is living in poverty with a wife and children, desperately trying to fend for himself and find work to buy food for his family. All for the crime of lending people a helping hand as he felt called to do by his Savior.

And now comes an elitist, high-paid, pampered professor from a prestigious university surrounded by luxury, enjoying all the finer things of life and going to the finest restaurants, working ridiculously easy hours, with lots of leisure, time and money to travel. And what does this wealthy, influential professor do? Does he offer to help the poor man who has been persecuted unjustly by a godless, heartless government for the "crime" of helping others?

Why no, the professor simpers and whimpers that he is afraid of the homeless pastor who is out of work and has a hungry family with nowhere to go and no one to help them. And in an interview with a like-minded elitist blogger, this rich, comfortable professor who has all the comforts one can imagine -- things the poor pastor never even has dreamed of, brags of the high security at his lab and says that if he ever feels 'threatened' by this unfortunate penniless, harmless pastor, living in poverty and hiding somewhere in an unknown part of the world, why he will just call the police from the comfort of his luxurious home or his multi-million dollar fully equipped lab and they will arrest the homeless man so that he, the rich, pampered, powerful professor, can be even more comfortable surrounded by his art collection, his latest model car, his designer clothes, his plasma TV and his well-stocked wine cellar.

Here are the details: http://laiglesforum.com/pro-abort-pro-gay-marriage-duke-u-prof-threatens-to-sic-cops-on-detractors/2091.htm Please take the time to call or email Dr. Nicolelis and ask him why he is threatening a homeless pastor for adhering to the Bible in his beliefs? And why does he think that homosexuals should be obliged to remain in their dangerous lifestyle? Does he not know that many want to quit this lifestyle for health and safety reasons? You may also ask the good doctor whether he would like to report me too for the "crime" of speaking out against this outrage. Thank you and God bless. Don Hank

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ref: -0 tags: machine learning CMU slides tutorial date: 01-17-2011 05:05 gmt revision:2 [1] [0] [head]

http://www.autonlab.org/tutorials/ -- excellent

http://energyfirefox.blogspot.com/2010/12/data-mining-with-ubuntu.html -- apt-get!


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ref: -0 tags: automatic programming Greg date: 01-11-2011 07:00 gmt revision:0 [head]

The goal is to make a system that is capable of automatic debugging / design. It seems to me that a good bit of the work of designing and debugging such a program - which I imagine to be basically a set of heuristics triggered by certain situations - is mechanical, and hence could be automated.

First, debugging: Say your program doesn't compile. You look at the error message + location, look at the code, and change variables either there or in causally-connected code to fix the error. The knowledge of what to change basically involves a forward model of how the computer runs the program and experiential knowledge of what worked in the past. The former need not be encoded - the computer can simply run slightly different versions of the program and see what happens itself (aka 'taking the partial derivatives of a program'). The latter can be stored in a well-designed database.

Then your program crashes. Usually, you look at the code and run it on a model of the computer in your mind, checking at every point if the given data-path and code-path to see if it diverges from acceptable behavior. Maybe you instrument the code with printfs. Then, you look at the causally-connected code to see what can be changed to alleviated the error condition, or to make the code/datapath align with well-known programming patterns. Again, the computer does not need a model of itself - the computer can simply running the code as an interpreted language; everything is then instrumented. The well-known patterns can be entered by a human, or learned via experimentation (analogous to 'school' and 'hacking' to a person).

Now your program runs and compiles. But, it doesn't do what you want it to do - you see in one particular case there is an error. So, you look at the program, run it in your mind, and look at all the variables and codepaths that are causally related to producing that case, imagining what changes to each will do to the error. Possibly this involves changing the AST, adding an if-statement, etc. You poke around; eventually something works, if partially. The computer can do the same thing, via the well-instrumented interpreted language.

Eventually this produces spaghetti code (unless you're really smart, and predicted all this case-programming), and small tweaks break more things than they fix. Time to refactor - apply well-known invariant code transformations, or more generally look for simpler codepaths with the same effective datapaths. Perhaps you avoided it by using good initial programming patterns, found mostly through analogy with the real world (object-orientation, MVC etc). Again this is where a good memory of programming-patterns will serve well.

That's the gist. There is much more - namely, the importance of finding transforms that render problems and sub-problems linear, and the practical consideration that the end goal in much computer programming is itself found through iteration - but this email is long enough. What I've outlined probably doesn't look close to GA / EA, but in practice will most likely involve intense and random experimentation within each of the steps above, something that GA does a lot of. What should make it faster is that individual random experimentation is more constrained - smaller space to explore - and when possible memory can replace expending time and power on experimentation. To look at it another way, the project should move a feedback loop (write compile observe) from the human to the computer; this is OK as all the needed info is within the computer already; no outside interaction is needed (unlike, say physical evolution).

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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: work-0 tags: distilling free-form natural laws from experimental data Schmidt Cornell automatic programming date: 12-29-2010 05:06 gmt revision:3 [2] [1] [0] [head]

Distilling free-form natural laws from experimental data

  • putting this here so I don't forget it.
  • There critical step was to use partial derivatives to find 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?
    • 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 bulk solids (or even simpler) mathematical expressions / linkages.

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ref: -0 tags: automatic programming Herbert Simon date: 12-29-2010 04:43 gmt revision:1 [0] [head]

Whether Software Engineering Needs to Be Artificially Intelligent By Herbert Simon, author of __The Sciences of the Artificial__

  • He talks about many tasks & goals that, at least in 2010, (25 years later) seem relatively obvious:
    • There is aboundary between man and machine, and the automatic programming can make steps by moving the boundary toward peeople: e.g. incorporating shortcuts / macros whatever for the menial trivial tasks of programming.
      • I would imagine that garbage collection, automatic type inference to be two of these menial tasks. Alternately, you can look at the automatic GUI generators like Glade and MFC. But why progress so slow on this part? We haven't automated that much..
    • Must have a better language for formalizing desired program state, desired results. I agree! Programming languages still conflate the tasks of describing the data structures with the task of describing the desired end state..
      • He talks about writing desires, objectives in natural language. I don't find that all to likely..
    • Need a database of data representations from which to draw, code for the automatic programmer to copy into new programs.
      • Have thought about this, and storing what program snippets do seems very ill defined! We can remember in our vague memory, but perhaps that's because we choose relatively few building blocks for constructing larger structures (and these structures, in turn, are relatively few...)
  • A good example of moving the boundary between man and machine is the telephone exchange system. Initially, it was only operated by humans; later, it's mostly machines - it's become hard to find a human operator on the other end. The steps to this have been gradual, possibly due to the required effort, possibly due to institutional intertia.
    • In design "the informality gradually gets squeezed out".
  • The author tells that medical diagnosis, e.g. at the hands of caduceus, is well functional; looking back & at the present absence of expert systems in medicine, this statement seems overly optimistic.
    • That said, i do agree heartily with that a useful expert system "must be designed in an interactive mode for progressive modification of the sort that I have been describing"
  • Random: While moves in chess can be searched by traversing a tree, backgammon is not susceptible to the same approach. Hans Berliner, apparently in the 1980's devised a production program that was able to beat the world champion backgammon player. This was at least 10 years before Tesauro!

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ref: -0 tags: automatic programming myths prospects date: 12-29-2010 04:42 gmt revision:3 [2] [1] [0] [head]

Automatic Programming: Myths and Prospects by Charles Rich and Richard C Waters, 1988

  • "End user oriented automatic programming systems must be domain experts. In particular, it is not possible to describe something briefly unless the hearer knows as much about the domain as the speaker does and can therefore understand the words and fill in what was left out.
  • Authors enumerate three general classes of automatic programming:
    • Bottom up. Eg. writing in very high-level programming languages; as in {853}, tries to push the boundary of human-machine toward the human.
    • Narrow domain. Eg. expert systems in a limited domain.
    • Assistant. Eg. IDEs, documentation: possibly the most popular approach.
  • Back in the day (1958) automatic programming consisted of what we now call assemblers and compilers. hah!
  • "The problem with reqirements (and contracts) is that they cannot be complete." (There is implicit, unstated information, as well as straight unspecified information).
    • Applied to practical things which must interact with people - they give the example of an ATM - i think so much is in the head of the human that automatic programming / using some potentially stochastic means of generating code makes no sense. Better to use templates and libraries! I'm more interested in the automatic creation of heuristic systems.
  • Program design is not serial: it involves continuous interaction between the programmer and client, which serves to communicate the client's desire and DSK to the programmer.
    • An automatic progarmming system must pay close attention to the medium that supports the dialog between human and program. The meduim must be, effectively, a powerful tool. (think of the palm..)
  • "Most of the productivity improvements introduced by automatic programming will almost certainly be used to atack enormous programs, rather than huge programs". So, we'll forever be in need of more powerful programming tools!
  • At some point, a high-level programming language description of a problem & it's algorithm of solution is as short or shorter than the English prose description of what the programm is/was to do :: what other degrees of compression can be extracted?
    • That said, "An interesting research direction is the design of artificial languages that intentionally allow informality" (ala English).
    • These will most likely not be natural languages, though: look at schematics, mathematical formula. These are really DSLs...
  • Regarding example-based automatic programming (despite the fact that humans communicate through examples and analogies extensively, just look at this blog (for example!)): "Unfortunately, exept for toy problems, no one has been able to make an example based automatic programming system work, and there is reason to believe this failure is fundamental."
    • Why? No matter how many examples are provided, there is no way to gurantee generalization. Oh, but I should contest this!
  • "The problem of sythesizing a program satisfying a given specification is formally equivalent to finding a constructive proof of the specifications satisfiability. This is the idea behind deductive logic based automatic programmers"
  • "Transformational methods in some form are certain to be part of all future automatic programming systems."
  • Programers think in cliches - and in fact, this is a useful technique for solving many problems by inspection. Should be possible to embed cliches in an expert-auto-programming system.

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ref: -0 tags: artificial intelligence machine learning education john toobey leda cosmides date: 12-13-2010 03:43 gmt revision:3 [2] [1] [0] [head]

Notes & responses to evolutionary psychologists John Toobey and Leda Cosmides' - authors of The Adapted Mind - essay in This Will change Everything

  • quote: Currently the most keenly awaited technological development is an all-purpose artificial intelligence-perhaps even an intelligence that would revise itself and grow at an ever-accelerating rate until it enacts millennial transformations. [...] Yet somehow this goal, like the horizon, keeps retreating as fast as it is approached.
  • AI's wrong turn was assuming that the best methods for reasoning and thinking are those that can be applied successfully to any problem domain.
    • But of course it must be possible - we are here, and we did evolve!
    • My opinion: the limit is codifying abstract, assumed, and ambiguous information into program function - e.g. embodying the world.
  • Their idea: intelligences use a number of domain-specific, specialized "hacks", that work for limited tasks; general intelligence appears as a result of the combination of all of these.
    • "Our mental programs can be fiendishly well engineered to solve some problems because they are not limited to using only those strategies that can be applied to all problems."
    • Given the content of the wikipedia page (above), it seems that they have latched onto this particular idea for at least 18 years. Strange how these sorts of things work.
  • Having accurate models of human intelligence would achieve two things:
    • It would enable humans to communicate more effectively with machines via shared knowledge and reasoning.
    • (me:) The AI would be enhanced by the tricks and hacks that evolution took millions of years, billions of individuals, and 10e?? (non-discrete) interactions between individuals and the environment. This constitutes an enormous store of information, to overlook it necessitates (probably, there may be seriuos shortcuts to biological evolution) re-simulating all of the steps that it took to get here. We exist as a cashed output of the evolutionary algorithm; recomputing this particular function is energetically impossible.
  • "The long term ambition [of evolutionary psychology] is to develop a model of human nature as precise as if we had the engineering specifications for the control systems of a robot.
  • "Humanity will continue to be blind slaves to the programs evolution has built into our brains until we drag them into the light. Ordinarily, we inhabit only the versions of reality that they spontaneously construct for us -- the surfaces of things. Because we are unaware that we are in a theater, with our roles and our lines largely written for us by our mental programs, we are credulously swept up in these plays (such as the genocidal drama of us versus them). Endless chain reactions among these programs leave us the victims of history -- embedded in war and oppression, enveloped in mass delusions and cultural epidemics, mired in endless negative-sum conflict \\ If we understood these programs and the coordinated hallucinations they orchestrate in our minds, our species could awaken from the roles these programs assign to us. Yet this cannot happen if knowledge -- like quantum mechanics -- remains forever locked up in the minds of a few specialists, walled off by the years of study required to master it. " Exactly. Well said.
    • The solution, then: much much better education; education that utilizes the best knowledge about transferring knowledge.
    • The authors propose video games; this is already being tested, see {859}

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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 zdz
    • The corresponding CDF: 1e z or P(Z>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) N where Z=max nPow(ω 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: sine wave synthesis integrator date: 02-03-2010 05:52 gmt revision:1 [0] [head]

I learned this in college, but have forgotten all the details - Microcontroller provides an alternative to DDS

freq=F2πτ where τ is the sampling frequency. F ranges from -0.2 to 0.

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ref: -0 tags: foreign car repair stories date: 12-15-2009 04:53 gmt revision:0 [head]

I find this particular study of how things fail fascinating - http://foreignaffairs.us/solutions.php

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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: life-0 tags: IQ intelligence Flynn effect genetics facebook social utopia data machine learning date: 10-02-2009 14:19 gmt revision:1 [0] [head]


My theory on the Flynn effect - human intelligence IS increasing, and this is NOT stopping. Look at it from a ML perspective: there is more free time to get data, the data (and world) has almost unlimited complexity, the data is much higher quality and much easier to get (the vast internet & world!(travel)), there is (hopefully) more fuel to process that data (food!). Therefore, we are getting more complex, sophisticated, and intelligent. Also, the idea that less-intelligent people having more kids will somehow 'dilute' our genetic IQ is bullshit - intelligence is mostly a product of environment and education, and is tailored to the tasks we need to do; it is not (or only very weakly, except at the extremes) tied to the wetware. Besides, things are changing far too fast for genetics to follow.

Regarding this social media, like facebook and others, you could posit that social intelligence is increasing, along similar arguments to above: social data is seemingly more prevalent, more available, and people spend more time examining it. Yet this feels to be a weaker argument, as people have always been socializing, talking, etc., and I'm not sure if any of these social media have really increased it. Irregardless, people enjoy it - that's the important part.

My utopia for today :-)

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ref: -0 tags: convert m4b to mp3 linux date: 09-11-2009 17:16 gmt revision:0 [head]

Recently I got an audiobook in m4b format, but I wanted to play it on my mp3 (only!) device. So, had to convert it. To do this, on my Debian Lenny box I first:

 apt-get install ffmpeg libmp3lame30 libfaad0 libavcodec51 

The last one seems to be the most important, nothing works even though libavcodec51 wold seem to have nothing to do with mp3 encoding... Then used a bash script:

for i in *.m4b; do
        ffmpeg -i "$i" -acodec libmp3lame "${i%m4b}mp3";

to convert all the m4b files in a directory. Later, I used easytag to add tags to the mp3s so they would show up properly on the device {770}. Simplest way to get this to work was to just change the name of the containing folder to Artist - Title; didn't want to manually change the tags on all the mp3's, and I didn't find a 'apply all' button.

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ref: life-0 tags: art design bantjes vector color date: 07-23-2009 14:14 gmt revision:0 [head]

Marian Bantjes - kickass designer. Just see her business card! or Saks snowflake theme

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ref: work-0 tags: ocaml toplevel ocamlfind date: 06-24-2009 14:52 gmt revision:1 [0] [head]

Ocaml has an interactive top level, but in order to make this useful (e.g. for inspecting the types of variables, trying out code before compiling it), you need to import libraries and modules. If you have ocamlfind on your system (I think this is the requirement..), do this with: #use "topfind";; at the ocaml prompt, then #require"package names" . e.g:

tlh24@chimera:~/svn/m8ta/yushin$ ledit | ocaml
        Objective Caml version 3.10.2

# #use "topfind";;
- : unit = ()
Findlib has been successfully loaded. Additional directives:
  #require "package";;      to load a package
  #list;;                   to list the available packages
  #camlp4o;;                to load camlp4 (standard syntax)
  #camlp4r;;                to load camlp4 (revised syntax)
  #predicates "p,q,...";;   to set these predicates
  Topfind.reset();;         to force that packages will be reloaded
  #thread;;                 to enable threads

- : unit = ()
# #require "bigarray,gsl";;
/usr/lib/ocaml/3.10.2/bigarray.cma: loaded
/usr/lib/ocaml/3.10.2/gsl: added to search path
/usr/lib/ocaml/3.10.2/gsl/gsl.cma: loaded
# #require "pcre,unix,str";;
/usr/lib/ocaml/3.10.2/pcre: added to search path
/usr/lib/ocaml/3.10.2/pcre/pcre.cma: loaded
/usr/lib/ocaml/3.10.2/unix.cma: loaded
/usr/lib/ocaml/3.10.2/str.cma: loaded
# Pcre.pmatch
- : ?iflags:Pcre.irflag ->
    ?flags:Pcre.rflag list ->
    ?rex:Pcre.regexp ->
    ?pat:string -> ?pos:int -> ?callout:Pcre.callout -> string -> bool
= <fun>
# let m = Gsl_matrix.create 3 3;;
val m : Gsl_matrix.matrix = <abstr>
# m;;
- : Gsl_matrix.matrix = <abstr>
# m.{1,1};;
- : float = 6.94305623882282e-310
# m.{0,0};;
- : float = 6.94305568087725e-310
# m.{1,1} <- 1.0 ;;
- : unit = ()
# m.{2,2} <- 2.0 ;;
- : unit = ()
# let mstr = Marshal.to_string m [] ;;


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ref: life-0 tags: princeton postmodern education kirn atlantic essay poetry undergrad date: 05-20-2009 05:32 gmt revision:1 [0] [head]

http://www.theatlantic.com/doc/200501/kirn -- goood.

  • quote: "Would it be possible someday—through drugs, maybe, or esoteric Buddhism, or some profound, postapocalyptic languor—to stop coming up with ideas of what we are and then laboring to live up to them?" -- from "The Autumn of the Multitasker". (The title makes me think of "Delta Autumn" by Faulkner, which I love...)

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ref: work-0 tags: flexible kapton funny date: 05-12-2009 21:57 gmt revision:3 [2] [1] [0] [head]

-- from the Lenthor Engineering Design guide. Wow they are indeed everywhere!

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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: -0 tags: processing javascript vector graphics web date: 05-03-2009 18:20 gmt revision:0 [head]

http://www.mattryall.net/blog/2008/11/wiki-visualisations-with-javascript -- way cool!!

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ref: -0 tags: recroding biopotential MOS-bipolar pseudoresistor date: 04-15-2009 22:03 gmt revision:0 [head]

Linear transconductor with rail-to-rail input swing for very large time constanct applications

  • Outlines the structure, theory, and use of MOS-bipolar pseudoresistors.
  • These devices can operate up to 330 GOhm!
  • Concise article.

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ref: Shadmehr-1997.01 tags: Shadmehr human long term memory learning motor M1 cortex date: 03-25-2009 15:29 gmt revision:2 [1] [0] [head]

PMID-8987766[0] Functional Stages in the Formation of Human Long-Term Motor Memory

  • We demonstrate that two motor maps may be learned and retained, but only if the training sessions in the tasks are separated by an interval of ~5 hr.
  • Analysis of the after-effects suggests that with a short temporal distance, learning of the second task leads to an unlearning of the internal model for the first.
  • many many citations!


[0] Shadmehr R, Brashers-Krug T, Functional stages in the formation of human long-term motor memory.J Neurosci 17:1, 409-19 (1997 Jan 1)

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ref: BrashersKrug-1996.07 tags: motor learning sleep offline consolidation Bizzi Shadmehr date: 03-24-2009 15:39 gmt revision:1 [0] [head]

PMID-8717039[0] Consolidation in human motor memory.

  • while practice produces speed and accuracy improvements, significant improvements - ~20% also occur 24hours later following a period of sleep. Why is this? We can answer it with the recording system!


[0] Brashers-Krug T, Shadmehr R, Bizzi E, Consolidation in human motor memory.Nature 382:6588, 252-5 (1996 Jul 18)

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ref: Debarnot-2009.03 tags: sleep motor imagery practice date: 03-24-2009 15:32 gmt revision:3 [2] [1] [0] [head]

PMID-18835655[0] Sleep-related improvements in motor learning following mental practice.

  • shows that after both physical practice and mental imagery on day 1, sleep improves test performance in both when testing on day 2.


[0] Debarnot U, Creveaux T, Collet C, Gemignani A, Massarelli R, Doyon J, Guillot A, Sleep-related improvements in motor learning following mental practice.Brain Cogn 69:2, 398-405 (2009 Mar)

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ref: Matsuzaka-2007.02 tags: skill learning M1 motor control practice cortex date: 03-20-2009 18:31 gmt revision:1 [0] [head]

PMID-17182912[0] Skill Representation in the Primary Motor Cortex After Long-Term Practice

  • The acquisition of motor skills can lead to profound changes in the functional organization of the primary motor cortex (M1) yes
  • 2 task modes: random target acquisition, and one of 2 repeating sequences (predictable, repeating mode)
  • 2 years of training -> 40% of units were differentially active during the two task modes
  • variations in movement types in the two classes did not fully explain the difference in activity between the 2 tasks
    • M1 neurons are more influence by the task than the actual kinematics.


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ref: notes-0 tags: wireless nordic headstage bridge neurorecord pictures photo EMG myopen date: 03-12-2009 02:33 gmt revision:4 [3] [2] [1] [0] [head]

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ref: Cooke-1990.03 tags: motor organization triphasic control EMG date: 03-11-2009 21:42 gmt revision:12 [11] [10] [9] [8] [7] [6] [head]

the organization of the human triphasic EMG control sequence:

  • PMID-2329356[0] Movement-related phasic muscle activation. II. Generation and functional role of the triphasic pattern.
  • PMID-8989378[1]
  • PMID-1629754[2]
  • PMID-2230915[3]
  • PMID-2329365[4]
  • PMID-2769335[5]
  • PMID-2769334[6]
  • PMID-3622686[7] Trajectory control in targeted force impulses. I. Role of opposing muscles.
    • Our findings emphasize that neuronal commands to opposing muscles acting at a joint must be adapted to constraints imposed by the properties of the neuromuscular plant.
  • PMID-10085332[8] Intersegmental dynamics are controlled by sequential anticipatory, error correction, and postural mechanisms.
    • frictionless air-jet system, rapid movements, inertia perturbation via masses on the joints, surprise trials.
    • surprise trials were well predicted by an open-loop feedforward controller.
    • there was feedback compensation upon return-to-center: it is not all feedforward (of course!)


[0] Cooke JD, Brown SH, Movement-related phasic muscle activation. II. Generation and functional role of the triphasic pattern.J Neurophysiol 63:3, 465-72 (1990 Mar)[1] Almeida GL, Hong DA, Corcos D, Gottlieb GL, Organizing principles for voluntary movement: extending single-joint rules.J Neurophysiol 74:4, 1374-81 (1995 Oct)[2] Gottlieb GL, Latash ML, Corcos DM, Liubinskas TJ, Agarwal GC, Organizing principles for single joint movements: V. Agonist-antagonist interactions.J Neurophysiol 67:6, 1417-27 (1992 Jun)[3] Corcos DM, Agarwal GC, Flaherty BP, Gottlieb GL, Organizing principles for single-joint movements. IV. Implications for isometric contractions.J Neurophysiol 64:3, 1033-42 (1990 Sep)[4] Gottlieb GL, Corcos DM, Agarwal GC, Latash ML, Organizing principles for single joint movements. III. Speed-insensitive strategy as a default.J Neurophysiol 63:3, 625-36 (1990 Mar)[5] Corcos DM, Gottlieb GL, Agarwal GC, Organizing principles for single-joint movements. II. A speed-sensitive strategy.J Neurophysiol 62:2, 358-68 (1989 Aug)[6] Gottlieb GL, Corcos DM, Agarwal GC, Organizing principles for single-joint movements. I. A speed-insensitive strategy.J Neurophysiol 62:2, 342-57 (1989 Aug)[7] Ghez C, Gordon J, Trajectory control in targeted force impulses. I. Role of opposing muscles.Exp Brain Res 67:2, 225-40 (1987)[8] Sainburg RL, Ghez C, Kalakanis D, Intersegmental dynamics are controlled by sequential anticipatory, error correction, and postural mechanisms.J Neurophysiol 81:3, 1045-56 (1999 Mar)[9] Seidler RD, Noll DC, Chintalapati P, Bilateral basal ganglia activation associated with sensorimotor adaptation.Exp Brain Res 175:3, 544-55 (2006 Nov)

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ref: Diedrichsen-2005.1 tags: Shadmehr error learning basal ganglia cerebellum motor cortex date: 03-09-2009 19:26 gmt revision:0 [head]

PMID-16251440[0] Neural correlates of reach errors.

  • Abstract:
  • Reach errors may be broadly classified into errors arising from unpredictable changes in target location, called target errors, and errors arising from miscalibration of internal models (e.g., when prisms alter visual feedback or a force field alters limb dynamics), called execution errors.
    • Execution errors may be caused by miscalibration of dynamics (e.g., when a force field alters limb dynamics) or by miscalibration of kinematics (e.g., when prisms alter visual feedback).
  • Although all types of errors lead to similar on-line corrections, we found that the motor system showed strong trial-by-trial adaptation in response to random execution errors but not in response to random target errors.
  • We used functional magnetic resonance imaging and a compatible robot to study brain regions involved in processing each kind of error.
  • Both kinematic and dynamic execution errors activated regions along the central and the postcentral sulci and in lobules V, VI, and VIII of the cerebellum, making these areas possible sites of plastic changes in internal models for reaching.
    • Only activity related to kinematic errors extended into parietal area 5.
    • These results are inconsistent with the idea that kinematics and dynamics of reaching are computed in separate neural entities.
  • In contrast, only target errors caused increased activity in the striatum and the posterior superior parietal lobule.
  • The cerebellum and motor cortex were as strongly activated as with execution errors. These findings indicate a neural and behavioral dissociation between errors that lead to switching of behavioral goals and errors that lead to adaptation of internal models of limb dynamics and kinematics.


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ref: Jackson-2007.01 tags: Fetz neurochil sleep motor control BMI free behavior EMG date: 03-06-2009 20:56 gmt revision:3 [2] [1] [0] [head]

PMID-17021028[0] Correlations Between the Same Motor Cortex Cells and Arm Muscles During a Trained Task, Free Behavior, and Natural Sleep in the Macaque Monkey

  • used their implanted "neurochip" recorder that recorded both EMG and neural activity. The neurochip buffers data and transmits via IR offline. It doesn't have all that much flash onboard - 16Mb.
    • used teflon-insulated 50um tungsten wires.
  • confirmed that there is a strong causal relationship, constant over the course of weeks, between motor cortex units and EMG activity.
    • some causal relationships between neural firing and EMG varied dependent on the task. Additive / multiplicative encoding?
  • this relationship was different at night, during REM sleep, though (?)
  • point out, as Todorov did, that Stereotyped motion imposes correlation between movement parameters, which could lead to spurrious relationships being mistaken for neural coding.
    • Experiments with naturalistic movement are essential for understanding innate, untrained neural control.
  • references {597} Suner et al 2005 as a previous study of long term cortical recordings. (utah probe)
  • during sleep, M1 cells exhibited a cyclical patter on quiescence followed by periods of elevated activity;
    • the cycle lasted 40-60 minutes;
    • EMG activity was seen at entrance and exit to the elevated activity period.
    • during periods of highest cortical activity, muscle activity was completely suppressed.
    • peak firing rates were above 100hz! (mean: 12-16hz).


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ref: Brown-2007.09 tags: motor force field learning vision date: 02-20-2009 00:28 gmt revision:1 [0] [head]

PMID-17855611 Motor Force Field Learning Influences Visual Processing of Target Motion

  • as you can see from the title - this is an interesting result.
  • learning to compensate for forces applied to the hand influenced how participants predicted target motion for interception.
  • subjects were trained on a robotic manipulandum that applied different force fields; they had to use the manipulandum to hit a accelerating target.
  • There were 3 force feilds: rightward, leftward, and null. Target accelerated left to right. Subjects with the rightward force field hit more targets than the null, and these more targets than the leftward force field. Hence motor knowledge of the environment (associated accelerations, as if there were wind or water current...) influenced how motion was perceived and acted upon.
    • perhaps there is a simple explanation for this (rather than their evolutionary information-sharing hypothesis): there exists a network that serves to convert visual-spatial coordinates into motor plans, and later muscle activations. The presence of a force field initially only affects the motor/muscle control parts of the ctx, but as training continues, the changes are propagated earlier into the system - to the visual system (or at least the visual-planning system). But this is a complicated system, and it's hard to predict how and where adaptation occurs.

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ref: Porro-1996.12 tags: motor imagery fMRI practice date: 02-19-2009 22:50 gmt revision:0 [head]

PMID-8922425 Primary Motor and Sensory Cortex Activation during Motor Performance and Motor Imagery: A Functional Magnetic Resonance Imaging Study.

  • says exactly what you might expect: that the motor cortex is active during motor imagery, and the regions active during motor performance and motor imagery are overlapping.

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ref: Tamaki-2008.02 tags: sleep spindle NREM motor learning date: 02-18-2009 17:44 gmt revision:0 [head]

PMID-18274267[0] Fast sleep spindle (13-15 hz) activity correlates with sleep-dependent improvement in visuomotor performance.

  • mirror-tracing task performance improves following a night's sleep.
  • the improvement is correlated with the fast-spindle activity.
  • spindles were detected from EEG recordings with a 10-16hz butterworth filter in matlab. Spindles had to be >= 15uv, >= 0.5s
    • slow spindles = 10-13Hz, predominant in the frontal regions.
    • fast spindles > 13hz, predominant in the parietal regions.


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ref: Morin-2008.08 tags: sleep spindles NREM motor learning date: 02-18-2009 17:35 gmt revision:2 [1] [0] [head]

PMID-18714787[0] Motor sequence learning increases sleep spindles and fast frequencies in post-training sleep.

  • as you can read in the title, it is the motor learning that increases the spindles. They did not look for causality in the opposite direction.
  • Task was finger-tap motor sequence learning, with control. Subjects had to type on a computer keyboard using the nondominant hand. No visual feedback was given during non-training performance (e.g. during practice).
  • Beta-frequencies are greater in sleep after motor learning. , though this is not correlated with actual consolidation.
  • Other studies have shown that spindles are also more frequent after spatial or verbal learning.
  • observed no effect of SWS on motor sequence learning.


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ref: Song-2009.01 tags: sleep motor learning consolidation attention date: 02-18-2009 17:28 gmt revision:1 [0] [head]

PMID-18951924[0] Consciousness and the consolidation of motor learning

  • Not all consolidation occurs during sleep; in some instances consolidation only occurs during the day; in other times, neither daytime or sleep consolidates a memory.
  • Attention is an important factor that may determine if sleep or daytime replay plays a role in consolidation.
  • In a tapping task, after a night of sleep performance is faster and more accurrate. Without the sleep, but with the same 12-hour interval, the same improvement is absent.
  • Evidence suggests though we experience the sensation of 'voluntary' movement, the conscious wish to move is more an afterthought than the cause.
    • Source: Libet et al 1983. (Subjects could accurately time events, and reported that the will to move preceded actual movement. However, the cortical potentials associated with movement preceded conscious awareness).
    • nonetheless, studies indicate that conscious awareness can affect movements, and how they are consolidated.
  • people with no declarative memory (like HR) can still remember procedural skills.
  • Consolidation = the process by which a fragile memory acquired via practice or exposure is consolidated into a more permanent, stable long-term form. If it occurs in the hours after practice, then it is 'off-line'; likewise for sleep.
    • Consolidation also includes stabilization, or making the memories robust to interference from new memories (retroactive interference).
    • This seems to be dependent on sleep, specifically NREM.
    • In studies where attention was broken using a tone counting task, neither over-night nor over-day enhancements were found to occur for motor sequence learning.
    • Another interesting effect is the development of explicit memory over the course of a night's sleep. Sleep seems to encourage conscious awareness of implicit patterns. -- probably through replay and integration.
  • Regarding "thinking too much" about sports: "As in the studies cited above, motor learning may initially rely on more explicit and prefrontal areas, but after extended practice and expertise, shift to more dorsal areas, but thinking about the movement can shift activity back to the less skilled explicit areas. Although many explanations may be derived, one could argue that these athletes show that even when years of practice has given the implicit system an exquisitely fine tuned memory for a movement, the explicit system can interfere at the time of performance and erase all evidence of implicit memory."
  • Well-written throughout, especially the conclusion paragraph.


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ref: Rasch-2009.06 tags: sleep cholinergic acetylcholine REM motor consolidation date: 02-18-2009 17:27 gmt revision:0 [head]

PMID-19194375[0] "Impaired Off-Line Consolidation of Motor Memories After Combined Blockade of Cholinergic Receptors During REM Sleep-Rich Sleep."

  • In REM sleep there is high, almost to wake-like, levels of ACh activity (in the cortex? they don't say).
  • Trained subjects on a motor task after a 3-hour period of slow wave sleep.
  • Then administered ACh (muscarinic + nicotinic) blockers or placebo
  • Subjects with blocked ACh reception showed less motor consolidation. So, ACh is needed! (This is consistent with Ach being an attentional / selective signal for activating the cortex).


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ref: Peters-2008.05 tags: Schaal reinforcement learning policy gradient motor primitives date: 02-17-2009 18:49 gmt revision:4 [3] [2] [1] [0] [head]

PMID-18482830[0] Reinforcement learning of motor skills with policy gradients

  • they say that the only way to deal with reinforcement or general-type learning in a high-dimensional policy space defined by parameterized motor primitives are policy gradient methods.
  • article is rather difficult to follow; they do not always provide enough details (for me) to understand exactly what their equations mean. Perhaps this is related to their criticism that others's papers are 'ad-hoc' and not 'statistically motivated'
  • none the less, it seems interesting..
  • their previous paper - Reinforcement learning for Humanoid robotics - maybe slightly easier to understand.


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ref: Mamassian-2008.06 tags: overconfidence human motor learning date: 02-17-2009 17:51 gmt revision:0 [head]

PMID-18578851 Overconfidence in an objective anticipatory motor task.

  • Participants were asked to press a key in synchrony with a predictable visual event and were rewarded if they succeeded and sometimes penalized if they were too quick or too slow.
  • If they had used their own motor uncertainty in anticipating the timing of the visual stimulus, they would have maximized their gain.
  • However, they instead displayed an overconfidence in the sense that they underestimated the magnitude of their uncertainty and the cost of their error.
  • Therefore, overconfidence is not limited to subjective ratings in cognitive tasks, but rather appears to be a general characteristic of human decision making. interesting! but is overconfidence really so bad?

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ref: notes-0 tags: Barto Hierarchal Reinforcement Learning date: 02-17-2009 05:38 gmt revision:1 [0] [head]

Recent Advancements in Hierarchal Reinforcement Learning

  • RL with good function-approximation methods for evaluating the value function or policy function solve many problems yet...
  • RL is bedeviled by the curse of dimensionality: the number of parameters grows exponentially with the size of a compact encoding of state.
  • Recent research has tackled the problem by exploiting temporal abstraction - decisions are not required at each step, but rather invoke the activity of temporally extended sub-policies. This is somewhat similar to a macro or subroutine in programming.
  • This is fundamentally similar to adding detailed domain-specific knowledge to the controller / policy.
  • Ron Parr seems to have made significant advances in this field with 'hierarchies of abstract machines'.
    • I'm still looking for a cognitive (predictive) extension to these RL methods ... these all are about extension through programmer knowledge.
  • They also talk about concurrent RL, where agents can pursue multiple actions (or options) at the same time, and assess value of each upon completion.
  • Next are partially observable markov decision processes, where you have to estimate the present state (belief state), as well as a policy. It is known that and optimal solution to this task is intractable. They propose using Hierarchal suffix memory as a solution ; I can't really see what these are about.
    • It is also possible to attack the problem using hierarchal POMDPs, which break the task into higher and lower level 'tasks'. Little mention is given to the even harder problem of breaking sequences up into tasks.
  • Good review altogether, reasonable balance between depth and length.

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ref: -0 tags: puerto rico rincon photo panorama date: 01-06-2009 23:28 gmt revision:2 [1] [0] [head]

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ref: -0 tags: san_juan puerto rico panorama photo date: 01-06-2009 06:18 gmt revision:4 [3] [2] [1] [0] [head]

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ref: Schicknick-2008.11 tags: dopamine plasticity auditory cortex date: 12-15-2008 04:13 gmt revision:1 [0] [head]

PMID-18321872[0] Dopaminergic Modulation of Auditory Cortex-Dependent Memory Consolidation through mTOR.

  • I will annotate this paper later, after winter break.


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ref: bookmark-0 tags: bell labs history DSP innovation invention date: 12-15-2008 04:12 gmt revision:0 [head]


  • again, to be annotated after break!

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ref: Churchland-2006.12 tags: motor_noise CNS Churchland execution variance motor_planning 2006 date: 12-08-2008 22:50 gmt revision:2 [1] [0] [head]

PMID-17178410[0] A central source of movement variability.

  • Small variations in preparatory neural activity were predictive of small variations in the upcoming reach
    • About half of the noise in reaching movements seems to be from variability during the preparatory phase, as estimated from regressions between preparatory neural activity and variability in performance.
  • even for a highly practiced task, the ability to repeatedly plan the same movement limits our ability to repeatedly execute the same movement.
  • when cocontraction increases, EMG variablility increases, but movement variability decreases. (This is consistent with poisson-based noise source?)
  • see the related articles!!


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ref: Froemke-2007.11 tags: nucleus basalis basal forebrain acetylcholine auditory cortex potentiation voltage clamp date: 10-08-2008 22:44 gmt revision:2 [1] [0] [head]

PMID-18004384[0] A synaptic memory trace for cortical receptive field plasticity.

  • nucleus basalis = basal forebrain!
  • stimulation of the nucleus basalis caused a reorganization of the auditory cortex tuning curves hours after the few minutes of training.
  • used whole-cell current-clamp recording to reveal tone-evoked excitatory and inhibitory postsynaptyic currents.
  • pairing of nucleus basalis and auditory tone presentation (2-5 minutes) increased excitatory currents and decreased inhibitory currents as compared to other (control) frequencies.
  • tuning changes required simultaneous tone presentation and nucleus basalis stimulation. (Could they indiscriminately stimulate the NB? did they have to target a certain region of it? Seems like it.)
    • did not require postsynaptic spiking!
  • Pairing caused a dramatic (>7-fold) increase in the probability of firing bursts of 2+ spikes
  • Cortical application of atropine, an acetylcholine receptor antagonist, prevented the effects of nucleus basalis pairing.
  • the net effects of nucleus basalis pairing are suppression of inhibition (20 sec) followed by enhancement of excitation (60 sec)
  • also tested microstimulation of the thalamus and cortex; NB pairing increased EPSC response from intracortical microstim, but not from thalamic stimulation. Both cortical and thalamic stimulation elicited an effect in the voltage-clamped recorded neuron.
  • by recording from the same site (but different cells), they showed that while exitation persisted hours after pairing, inhibition gradually increased commensurate with the excitation.
  • Thus, NB stimulation leaves a tag of reduced inhibition (at the circuit level!), specifically for neurons that are active at the time of pairing.


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ref: Karni-1998.02 tags: motor learning skill acquisition fMRI date: 10-08-2008 21:05 gmt revision:1 [0] [head]

PMID-9448252[0] The acquisition of skilled motor performance: Fast and slow experience-driven changes in primary motor cortex

  • a few minutes of daily practice on a sequential finger opposition task induced large, incremental performance gains over a few weeks of training
  • performance was lateralized
  • limited training experience can be sufficient to trigger performance gains that require time to become evident.
  • learning is characterized by two stages:
    • "fast” learning, an initial, within-session improvement phase, followed by a period of consolidation of several hours duration
      • possibly this is due to synaptic plasticity.
    • and then “slow” learning, consisting of delayed, incremental gains in performance emerging after continued practice
      • In many instances, most gains in performance evolved in a latent manner not during, but rather a minimum of 6–8 hr after training, that is, between sessions
      • this is thought to correspond to the reorganization of M1 & other cortical structures.
  • long-term training results in highly specific skilled motor performance, paralleled by the emergence of a specific, more extensive representation of a trained sequence of movements in the contralateral primary motor cortex. this is seen when imaging for activation using fMRI.
  • why is there the marked difference between declarative learning, which often only takes one presentation to learn, and procedural memory, which takes several sessions to learn? Hypothetically, they require different neural substrates.
  • pretty good series of references...


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ref: -0 tags: blind seeing tongue plasticity learning date: 10-08-2008 17:49 gmt revision:1 [0] [head]

“Seeing” through the tongue: cross-modal plasticity in the congenitally blind

  • tested their tongue display unit on sighted and blind volunteers; the blind volunteers showed increased PET signal in their occipital lobe, while the sighted (blindfolded) volunteers did not, though both achieved the same levels of performance on a orientation discrimination task after one week of intensive training.
  • TDU unit has 144 contacts.
  • spatial learning with this is apparently robust and rapid with people!

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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: Schultz-2000.03 tags: review orbitofrontal cortex basal ganglia dopamine reward reinforcement learning striatum date: 10-07-2008 03:53 gmt revision:1 [0] [head]

PMID-10731222[0] Reward processing in primate orbitofrontal cortex and basal ganglia

  • Orbitofrontal neurons showed three principal forms of reward-related activity during the performance of delayed response tasks,
    • responses to reward-predicting instructions,
    • activations during the expectation period immediately preceding reward and
    • responses following reward
    • above, reward-predicting stimulus in a dopamine neuron. Left: the animal received a small quantity of apple juice at irregular intervals without performing in any behavioral task. Right: the animal performed in an operant lever-pressing task in which it released a touch-sensitive resting key and touched a small lever in reaction to an auditory trigger signal. The dopamine neuron lost its response to the primary reward and responded to the reward-predicting sound.
  • for the other figures, read the excellent paper!


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

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

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


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ref: Nakahara-2001.07 tags: basal ganglia model cerebral cortex motor learning date: 10-05-2008 02:38 gmt revision:0 [head]

PMID-11506661[0] Parallel cortico-basal ganglia mechanisms for acquisition and execution of visuomotor sequences - a computational approach.

  • Interesting model of parallel motor/visual learning, the motor through the posterior BG (the middle posterior part of the putamen) and supplementary motor areas, and the visual through the dorsolateral prefrontal cortex and the anterior BG (caudate head and rostral putamen).
  • visual tasks are learned quicker due to the simplicity of their transform.
  • require a 'coordinator' to adjust control of the visual and motor loops.
  • basal ganglia-thalamacortical loops are highly topographic; motor, oculomotor, prefrontal and limbic loops have been found.
  • pre-SMA, not the SMA, is connected to the prefrontal cortex.
  • pre-SMA receives connections from the rostral cingulate motor area.
  • used actor-critic architecture, where the critic learns to predict cumulative future rewards from state and the actor produces movements to maximize reward (motor) or transformations (sensory). visual and motor networks are actors in visual and motor representations, respectively.
  • used TD learning, where TD error is encoded via SNc.
  • more later, not finished writing (need dinner!)


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ref: Hikosaka-2002.04 tags: motor learning SMA basal ganglia M1 dopamine preSMA review date: 10-05-2008 02:06 gmt revision:1 [0] [head]

PMID-12015240[0] Central mechanisms of motor skill learning

  • review article.
  • neurons in the SMA become active at particular transitions in sequential movements; neurons in the pre-SMA maybe active specifically at certain rank orders in a sequence.
    • Many neurons in the preSMA were activated during learning of new sequences
  • motor skill learning is associated with coactivation of frontal and partietal cortices.
  • With practice, accuracy of performance was acquired earlier than speed of performance. interesting...
  • Striatum:
    • Reversible blockade of the anterior striatum (associative region) leads to deficits in learning new sequences
    • blockade of the posterior striatum (motor region) leads to disruptions in the execution of learned sequences
  • Cerebellum: In contrast, blockade of the dorsal part of the dentate nucleus (which is connected with M1) does not affect learning new sequences, but disrupts the performance of learned sequences. The conclude from this that long-term memories for motor skills ma be storerd in the cerebellum.
  • Doya proposed that learning in the basal ganglia and cerebellum maybe guided by error signals, as opposed to the cerebral cortex.


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ref: Graybiel-1994.09 tags: basal ganglia graybeil expert systems motor learning date: 10-03-2008 22:18 gmt revision:2 [1] [0] [head]

PMID-8091209[0] The basal ganglia and adaptive motor control (I couldn't find the pdf for this)

  • the basal ganglia is essentially an expert system which is trained via dopamine.


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ref: Dayan-2002.1 tags: actor critic pavlovian learning basal ganglia date: 10-03-2008 19:33 gmt revision:1 [0] [head]

PMID-12383782[0] Reward, motivation, and reinforcement learning.

  • criticism of the actor-critic model in the context of extensive behavioral research.
    • the critic evaluates the average future reward of given states (for the whole task - hence solving the temporal credit problem.
  • discusses temporal credit problem, which is an issue in sequential learning problems. (and nearly all learning!)
  • heheh: "For example, Hershberger, W.A., 1986. An approach through the looking glass. Anim. Learn. Behav. 14, pp. 443–451. View Record in Scopus | Cited By in Scopus (9)Hershberger (1986) trained cochral chicks to expect to find food in a specific food cup. He then arranged the situation such that if they ran toward the food cup, the cup receded at twice their approach speed whereas if they ran away from the food cup, it approached them at twice their retreat speed. As such, the chicks had to learn to run away from the distinctive food cup in order to get food. Hershberger found that the chicks were unable to learn this response in order to get the food and persisted in chasing the food away. They could, however, learn perfectly well to get the food when the cup moved away from them at only half of their approach speed."


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ref: Graybiel-2005.12 tags: graybiel motor_learning reinforcement_learning basal ganglia striatum thalamus cortex date: 10-03-2008 17:04 gmt revision:3 [2] [1] [0] [head]

PMID-16271465[] The basal ganglia: Learning new tricks and loving it

  • learning-related changes occur significantly earlier in the striatum than the cortex in a cue-reversal task. she says that this is because the basal ganglia instruct the cortex. I rather think that they select output dimensions from that variance-generator, the cortex.
  • dopamine agonist treatment improves learning with positive reinforcers but not learning with negative reinforcers.
  • there is a strong hyperkinetic pathway that projects directly to the subthalamic nucleus from the motor cortex. this controls output of the inhibitor pathway (GPi)
  • GABA input from the GPi to the thalamus can induce rebound spikes with precise timing. (the outputs are therefore not only inhibitory).
  • striatal neurons have up and down states. recommended action: simultaneous on-line recording of dopamine release and spike activity.
  • interesting generalization: cerebellum = supervised learning, striatum = reinforcement learning. yet yet! the cerebellum has a strong disynaptic projection to the putamen. of course, there is a continuous gradient between fully-supervised and fully-reinforcement models. the question is how to formulate both in a stable loop.
  • striosomal = striatum to the SNc
  • http://en.wikipedia.org/wiki/Substantia_nigra SNc is not an disorganized mass: the dopamergic neurons from the pars compacta project to the cortex in a topological map, dopaminergic neurons of the fringes (the lowest) go to the sensorimotor striatum and the highest to the associative striatum


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ref: Radhakrishnan-2008.1 tags: EMG BMI Jackson motor control learning date: 10-03-2008 16:45 gmt revision:0 [head]

PMID-18667540[0] Learning a novel myoelectric-controlled interface task.

  • EMG-controlled 2D cursor control task with variable output mapping.
  • Subjects could learn non-intuitive output transforms to a high level of performance,
  • Subjects preferred, and learned better, if hand as opposed to arm muscles were used.


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ref: Li-2001.05 tags: Bizzi motor learning force field MIT M1 plasticity memory direction tuning transform date: 09-24-2008 22:49 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-11395017[0] Neuronal correlates of motor performance and motor learning in the primary motor cortex of monkeys adapting to an external force field

  • this is concerned with memory cells, cells that 'remember' or remain permanently changed after learning the force-field.
  • In the above figure, the blue lines (or rather vertices of the blue lines) indicate the firing rate during the movement period (and 200ms before); angular position indicates the target of the movement. The force-field in this case was a curl field where force was proportional to velocity.
  • Preferred direction of the motor cortical units changed when the preferred driection of the EMGs changed
  • evidence of encoding of an internal model in the changes in tuning properties of the cells.
    • this can suppor both online performance and motor learning.
    • but what mechanisms allow the motor cortex to change in this way???
  • also see [1]


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ref: Zhu-2003.1 tags: M1 neural adaptation motor learning date: 09-24-2008 22:17 gmt revision:0 [head]

PMID-14511525 Probing changes in neural interaction during adaptation.

  • looking at the changes in te connectivity between cells during/after motor learning.
  • convert sparse spike trains to continuous firing rates, use these as input to granger causality test
  • used the Dawn Taylor monkey task, except with push-buttons.
  • perterbed the monkey's reach trajectory with a string to a pneumatic cylinder.
  • their data looks pretty random. 9-17 neurons recorded. learning generally involves increases in interaction.
  • sponsored by DARPA
  • not a very good paper, alas.

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ref: Maravita-2004.02 tags: tool use monkey mirror neurons response learning date: 09-24-2008 17:02 gmt revision:2 [1] [0] [head]

PMID-15588812[0] Tools for the body schema

See also PMID-8951846[1] Coding of modified body schema during tool use by macaque postcentral neurones.


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ref: Narayanan-2005.04 tags: Laubach M1 motor rats statistics BMI prediction methods date: 09-07-2008 19:51 gmt revision:4 [3] [2] [1] [0] [head]

PMID-15858046[] Redundancy and Synergy of Neuronal Ensembles in Motor Cortex

  • timing task.
  • rats.
  • 50um teflon microwires in motor cortex
  • ohno : neurons that were the best predictors of task performance were not necessarily the neurons that contributed the most predictive information to an ensemble of neurons.
  • most all contribute redundant predictive information to the ensemble.
    • this redundancy kept the predictions high, even if neurons were dropped.
  • small groups of neurons were more synergistic
  • large groups were more redundant.
  • used wavelet based discriminant pursuit.
    • validated with draws from a random data set.
  • used R and Weka
  • data looks hella noisy ?


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ref: notes-0 tags: robots Tokyo Institute of Technology date: 09-04-2008 17:30 gmt revision:5 [4] [3] [2] [1] [0] [head]

Robots & others designed & made at the Tokyo Institute of Technology (from the Hirose / Fukushima Robotics lab)

  • snake robots
  • gripper
      • with human-crushing, kid-grabbing power. frightening!
  • walking robots
      • -- 1994. can climb a 70 degree slope!
    • --window washing robot.
    • -- skating robot: walk ; skate. movie -- wow!
  • wheeled robots
  • other
    • -- prismatic, variable-speed eccentric linear drive. sorta like harmonic drive for linear motion? link

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ref: -0 tags: LDA PCA autoregressive EMG date: 07-29-2008 23:35 gmt revision:3 [2] [1] [0] [head]

Below, emg classification by computing the autoregressive coefficients and feeding them into linear discriminant analysis (LDA). LDA code from here; data in myopen svn. Nine classes of movement in the data, 4 repetitions of each. The input data is 16-dimensional: 4 AR coefficients per 4 channels. This is consistent with Blair Lock's thesis.

For reference, here is an imagesc() of the raw coefficients (the 4 different color bands correspond to the 4 different channels):

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ref: notes-0 tags: expectation maximization EM clustering autosorting date: 06-16-2008 19:40 gmt revision:5 [4] [3] [2] [1] [0] [head]

so, I coded up the EM algorithm - it was not hard, though i did have to put the likelihood calculation in C++ because i couldn't figure out how to vectorize it properly. It fits the clusters pretty well, but it does not tell you how many clusters there are!

clustering with 5 underlying gaussians:

plot of the log-likelihood of fitted gaussian mixtures vs. number of gaussians:

the code is in subversion, of course.

James has code for gibbs-sampling to the correct number of components! Here is an example of the output - it quickly removes the unnecessary gaussian components:

images/227_4.pdf -- original CEM (classification expectation maximization) paper, 1992, by Celeux and Govaert. Note that CEM with no variance estimation and gaussian clusters is the same as k-means, see {224}. See also http://klustakwik.sourceforge.net/

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ref: Walker-2005.12 tags: algae transfection transformation protein synthesis bioreactor date: 03-21-2008 17:22 gmt revision:1 [0] [head]

Microalgae as bioreactors PMID-16136314

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ref: engineering notes-0 tags: BGA PCB design blueCore bluetooth laser drilling CSR via clearance date: 03-19-2008 22:35 gmt revision:4 [3] [2] [1] [0] [head]

This is from the CSR reference design for the BlueCore5 chip.

They also note that you have to pay attention to the aspect ratio of the vias - with laser drilling, this means that they needed a 63um prepreg between layers 1 and 2 (ground), with start copper thickness of 18um.

PTH = plated-through-hole. (refers to a type of via)

For 0.8mm BGA, you can loosen the design rules to the following: "

Minimum track width0.125mm(*) local, 0.15mm global0.005"
Minimum clearance0.125mm(*)0.005"
Minimum thru-hole0.15mm hole, 0.4mm landing under BGA0.006" on 0.016"
0.25mm hole, 0.6mm landing global0.01" on 0.024"
Solder Mask opening0.075mm radius opening around pads0.003"
(*) note: For a 0.8mm BGA with 0.4mm diameter pads, this could technically be 0.133mm, but I prefer to round to 1/8mm or just about 0.005"

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ref: notes-0 tags: two-photon laser imaging fluorescence lifetime imaging FRET GFP RFP date: 01-21-2008 17:23 gmt revision:0 [head]


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ref: engineering notes-0 tags: bluetooth CSR NXP headset radio telemetry 802.11 zigbee low-power date: 12-12-2007 06:10 gmt revision:26 [25] [24] [23] [22] [21] [20] [head]

the contenders:

  • NXP BGB210S, a 4th generation chip from Philip's spin-off NXP.
    • 3 x 5 x 1 mm (!!).
    • supports Bluetooth 2.0 + EDR.
      • the higher data rate is really targeted at decreasing the TX active time.
    • power consumption: 12ma @ 1.8v supply = 21.5mW
    • CMOS w/ near-zero intermediate frequency radio.
  • BGW211 802.11 system-on-a-chip, from NXP
    • 400mw Tx power, 300mw Rx - both too much, me thinks.
  • BCM4326
    • similar power figures (295mw rx, 425mw tx)
    • ultra-small 0.25mm WLCSP (!!)
    • one chip solution for 802.11b/g ; BCM4328 supports 802.11a, too.
  • Wi2wi w2cbw003 - 230ma tx, 210ma rx 802.11 module. too much.
  • G2 Microsystems , developers of 802.11B (11mbps) system-on-a-chip for RFID.
    • insanely low power dissipation! years on AA batteries! (based on 40s interval between data transmissions. 1.3mJ per transmission - an order of 500 lower than existing solutions. much lower static dissipation, too.
    • includes 32 bit RISC processor with 80kb ram, 320 kb flash/rom.
    • works with existing infrastructure, e.g. cisco.
    • article on the chip / product, may 2006.
    • http://www.gainspan.com/ -- competitors. they do not appear to have a product yet.
  • Freescale LP1070FC 802.11a/b/g, requires external PA, LNA, switch. no data on the power consumption... actually, the datasheet appears to be rather incomplete!
  • CSR UniFi-1 radio is far better, but I can't seem to find documentation for that, specifically the power dissipation.
    • well, let's see - 20 hours talk time with a 1500mAH battery = 75ma. not bad, i guess; TX power can be decreased for the short range we need.
  • BlueCore5 ; product brief, which includes more power info.
    • rather recently developed; is the silicon debugged? The datasheet is preliminary information.
    • 10 x 10mm, 0.8mm pitch 105 balls or 8x8 TFBGA.
    • 1.5V core, 1.8V-3.6V io, USB
    • bluetooth v2.0/2.1.
    • 64mips DSP on-chip.
      • 0.3 mA/MIPS at 1.5V. compare to Texas instruments TMS320VC5507 = 0.45ma/Mhz @ 1.2V core ~= 54Mw at 100mips; Kalimba ~= 30mw @64mips.
      • this is 2mips/channel. enough? damn, gotta keep the power low!
      • the Bluecore3 datasheet has more information on the DSP power consumption.
    • 16 Mbit flash, too!
    • BlueCore4 seems to be much better documented, but it does not include the DSP, which saves a lot on parts count.. as well as power.
  • Bluecore4
    • 8x8mm 96-bga,
    • with 6mbit flash!
    • bluetooth 2.0 / EDR.
    • current consumption of about 26ma @ 1.8V supply when in SCO HV3
  • Boroadcom BCM4326
    • single chip 802.11b/g solution, integrated Arm7 CPU
    • again, 300mW (not mA! smaller!) Rx, 400 mW Tx. That's still a lot of power.
  • Broadcom BCM2047
    • again, seems that these have yet to come out; details are scarce.
    • The belkin bluetooth 2.0 adapter that I bought at compusa uses a BCM2045.
  • CC2400, non-bluetooth - simpler!
  • Zarlink - ultra low power, 433Mhz ISM band biomedical tranciever.
    • about 7x7mm.
    • 3v supply, 2.7 should work, 5ma = 13.5mw (yesss!)
    • 800kbps raw data rate, max.
    • 2.45Ghz wakeup reciever (??)
    • seems to be designed for pacemakers & neurostimulators.
    • need to contact zarlink for the full data sheet.
  • RFM TR1100 - what the wolf lab uses for telemetry. OOK or ASK.
    • 1Mbps max.
    • only 1 channel, so far as i can tell...
    • 8ma @ 2.7V = 21.6mw.
    • integrated SAW filters = narrow bandwidth.
    • 10 x 6 mm size, minimal external components, though it does seem to require extra resistors.
    • really interesting method of obtaining RX input amplification stability - a SAW delay line, where the amplifiers are pulsed on at different times to permit the passage of RF energy. quote: "rf stability is obtained by distributing RF gain over time", as opposed to the superheterodyne solution of distributing gain over frequencies. If there were 100db of gain in 1 frequency, the amplifier is very likely to oscillate.
  • RFM TRC101
  • RFM TR3100 576 kbps ASK, -85dbm 10e-3 error rate.
    • 10ma TX / 7ma RX
    • 11x9,65mm SM-20L package
    • kinda has a lot of external components.
    • 434 mhz operation.
  • ADF7025 Analog 431-464, 862-870, 902-928 ISM band FSK transceiver.
    • 20ma TX (28ma at +10dbm) , 20ma RX from 2.3 to 3.6V supply.
    • direct conversion: zero IF.
    • SPI interface (plus a bunch of other signals).
    • 384kbps max data rate.
    • 7mm x 7mm 48 lead CSP
  • CC1101 (chipcon was acquired by TI)
    • 500kbps FSK, GFSK, MSK, OOK, ASK transmit/receive. 500kbps is only available in MSK, minimum-shift keying mode.
      • -84dbm receiver sensitivity @ 500kbps.
    • same bands as above + a bit more margin.
    • suitable for frequency hopping systems.
    • QLP 4mm x 4mm package
    • 16ma TX (32.3 at +10dbm), 16ma RX
    • 1.8 - 3.6V operation.
  • Freescale MC13192, Zigbee compliant transciever, 2.405 - 2.480 Mhz, 5mhz channels, 2Mchip/sec over the air data rate, 200kbps practical rate.
    • 30ma TX @ 0dbm, 37ma RX.
    • 5mm x 5mm package
    • full Zigbee PHY support.
    • similar device from ember - 35ma TX / 35ma RX, 2.1-3.5V, 7x7mm, includes microprocessor.
    • MC13201 - also targeted at 802.15.4 compliance.
      • good to 250kbps, 5.0 mhz channels, DSSS, 2.0 - 3.4V,
      • requires external transmit/receive switch
      • 30ma TX / 37ma RX
      • 5 x 5mm package
  • TI / Chipcon CC2430 - 27ma TX / 27ma RX, with microcontroller, 7x7mm package, quick power-up.
  • Cypress wireless USB
    • 2.4ghz, 1mbps, DSSS encoding (like zigbee) -- DSSS reduces the data rate, of course; the data rate over the air is always 1mbps.
      • the favored rate is 8x DSSS, where each symbol encodes one byte (8 bits) but requires 32 or 64 chips for transmission (resulting in a net rate of 250kbsp or 125 kbps, like zigbee. )
    • 21ma normal operating current @-5dbm, 1.8V to 3.6V
    • 6mm x 6mm 40-lead package
    • document above is a generally good overview of the complexities of this type of design.
  • SC1211
    • 110kbps, UHF transceiver (~863 - 960mhz). very low power consumption in RX: 3ma / TX: 25ma @ +10dbm out
    • out November 2007.
    • competitor to below -- much lower RX power (and lower rate).
    • includes 64byte fifo, data whitening, etc.
  • advance info from Maxim
    • very low power TX: 4ma @ -10dbm, RX: 150ua Hey.. that's lower power than most PLL, VCO, & PA put together!
    • OOK, ~116kbps.
  • Nordic nRF24L01 - THE BEST (so far!)
    • datasheet.
    • 12ma TX/RX, 2.1 3.6V
    • 2mbps over-the-air rate, GFSK, 10m range (better with a bigger antenna)
    • 4x4mm 20 pin package.
    • 125 selectable channels.
    • allows clock sharing with a microprocessor, e.g. the blackfin, provided it exceeds the 60ppm specification.
    • 22ua power consumption in standby-1 mode (transition from this state to RX/TX in 130us), 320ua power consumption in standby-2 mode (ready to transition to TX)
      • it is important to never keep the nRF24L01 in TX mode for more than 4ms at a time (!)
    • i think the designer's confidence showes through the specification sheet: they are proud of the chip & it's specifications, which is a very good thing. it means they put some pride and passion into it.
    • development board - need to buy! They also [distribute the IC http://www.sparkfun.com/commerce/product_info.php?products_id=690], yay!

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ref: bookmark-0 tags: IEC fusion Bussard tokamak date: 10-31-2007 22:38 gmt revision:2 [1] [0] [head]

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ref: bookmark-0 tags: bluetooth tutorial specification date: 10-22-2007 16:56 gmt revision:1 [0] [head]


  • has concise details for how the apparently complex bluetooth protocol functions.
Taking a walk inside blutooth EDR
  • bluetooth 1 - 1.2 (1mbps) uses gaussian frequency-shift keying (GFSK), with a frequency deviation of +-160khz
  • bluetooth 2.0 EDR (2mbps) uses pi/4 differential quaternary phase-shift keying (DQPSK). The receiver does not have to know the phase of the transmitter for this. Two bit are transmitted per symbol with this scheme; hence the symbol rate stays the same as bluetooth 1.
  • bluetooth 2 (3mbps) uses 8-differential phase-shift keying to transmit 3 bits / symbol, with the same effective symbol rate. The receiver must know the phase of the transmitter.
  • each of these modulation formats is specified in the packet header, and communication rate is negotiated upon establishing a connection.

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ref: notes-0 tags: NewYorker healthcare Clinton date: 10-08-2007 02:34 gmt revision:1 [0] [head]

be forewarned : this is poorly organized!

From the New Yorker, October 1 2007:

"We've been here before, but this time the stars are really coming into alignment. Our health-care system has continued to deteriorate. We spend twice as much as the French and the Germans and two and a half times as much as the Brits, yet we dies sooner and our babies die in greater numbers. Thirty-eight million americans were uninsured in 200; now it's 47M. Employer-bnased health insurance is increasingly expensive, stingy, and iffy. Companies, especially manufacturing companies, are beginning to realize that being deputized to pay the health-care costs of their employees and retirees puts them at a competitive disadvantage in the global economy. "

Therefore, then there will be two segments of the population supportive of centralized / federalized health care: the workers (myself one, i have to pay for health insurance myself; its (BCBSNC) costs ~$160/month and I can't be certian of it's quality or coverage just yet), and the employers. The employers have seen an increase of 63% for single coverage and 58% for family coverage since 2001.[1] Who else is there? oh, yea, the healthcare industry ( $224 billion in biotech 2000, $184B spent on pharmaceuticals 2003, $606B by private health insurance, which made $209B in profits) also, how are we going to fund this? Medicare has $30 Trillion in unfunded liability, which is three times that of the US mortgage debt.

Ultimately, i think the problem is that the government and private insurance do not want to pay for the uninsured, but when such a situation occurs, they are morrally obliged to do so, and hence much somehow subsidize / hide the costs of this. It is argued that if everyone was provided with basic healthcare through the government, then the difficulty and inefficiency of hiding the cost would be avoided.

  • Medicare finances health care for ~40 Million Americans, accounting for 1/8 of all federal expenditures. Unless our health care system becomes more efficient, it will take more than all of the federal budget to cover our entire population - and this does not consider the aging baby-boomer generation. Furthermore, Medicad / Medicare, which spends about 2% of it's budget on administration, is generally more efficient than private health insurance, which spends more than 15% on the same (those figures from the New Yorker; [1] lists it closer to 26%, but this icludes malpractice insurance)
  • The US healthcare industry subsidizes the development of drugs for a large part of the rest of the world, where government price controls limit / eliminate compensation the cost of pharmaceutical R&D.
  • and what are you going to do with all the employees of present healthcare insurance corporations?
  • federalized health insurance would decrease the malpractice liability, as (hopefully) juries would realize that the money for settlements is, in effect, coming out of their own collective pocket, and will not be there to do more worthwile things.
http://www.ndu.edu/ICAF/Industry/reports/2005/pdf/2005_HCIS.pdf -- really excellent resource!

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ref: bookmark-0 tags: architecture travel places to see Spencer Tunic date: 09-18-2007 14:28 gmt revision:1 [0] [head]

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ref: bookmark-0 tags: I2S bust serial protocol DAC date: 08-27-2007 16:54 gmt revision:0 [head]


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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: photo-0 tags: picture photo NYC lisa date: 06-03-2007 16:49 gmt revision:0 [head]

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ref: bookmark-0 tags: bluetooth SCO ACL TCP FEC DH1 date: 05-28-2007 20:11 gmt revision:0 [head]

  • paper which suggests that voice and other data should be carried over ACL links rather than SCO links, thus making the protocol and bandwidth allocation simpler.
    • explains how HV1 is high-quality voice and is protected by 1/3 forward-error-encoding. HV3, in contrast, has no encoding/ no error correction schemes, hence is lower power (less transmit time).
    • ACL links mus precede SCO links in bluetooth.
    • DH1 packets good for TCP.. what's DH1?
  • Setting up a bluetooth packet transport link
    • excellent background information :) !
    • also only examines ACL links.
    • DH1 are single-slot packets of 30 bytes each, which have no FEC encoding
    • the question why the bluetooth protocol is so comlicated.. good question indeed!

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ref: notes-0 tags: kicad footprint generator pcb design date: 05-22-2007 02:51 gmt revision:1 [0] [head]

oh yea!!! nice work mate!!


btw, kicad is the shit - and it is now in Debian!! I love debian! I love kicad!

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ref: engineering-0 tags: bluetooth rfcomm sco headset date: 04-30-2007 02:03 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

An experiment with bluetooth, jabra, and hypothetical wireless lowfi neural recording:

  • Gary suggested Thursday (April 27 2007) to use a bluetooth headset adapter to telemeter neural signals, I decided to try it out. I went to compusa, bought the cheapest bluetooth headset i could find (a Jabra BT135, verizon branded, 8 hour talk 170 hour standby, 14 grams, retro-futuristic design release your inner jabra etc. etc.), charged it, and spent many hours fiddling with it and bluetooth-alsa ( http://bluetooth-alsa.sourceforge.net/build.html ), the latter to no avail.
  • This is despite the fact that after doing something like sudo apt-get install bluez* and sudo apt-get install kbluetooth then kbluetoothd (this daemon & gui element is rather useful, werks good even in xfce4! It has a receive power meter, too, from which i estimate that the headsets won't work >1m or so), hciconfig lists my DLink DBT-120 correctly, and as far as i can tell, fully supports it and hcitool cc 00:16:8F:BF:7B:E0 seems to correctly pair with my device (and that bluetooth support in the 2.6.18 (debian) kernel is rather mature through BlueZ). (that said, i finally got the gtk pin window with carwhisperer, to be discussed later, and ever since then it has worked well -- perhaps the PIN entered into /etc/bluetooth/hcid.conf was not used?). For reference, here is my functional hcid.conf: (note that I've changed the class of the host adapter to be that of a cell phone for proper pairing)
   # HCId options
options {
        # Automatically initialize new devices
        autoinit yes;

        # Security Manager mode
        #   none - Security manager disabled
        #   auto - Use local PIN for incoming connections
        #   user - Always ask user for a PIN
        security auto;

        # Pairing mode
        #   none  - Pairing disabled
        #   multi - Allow pairing with already paired devices
        #   once  - Pair once and deny successive attempts
        pairing multi;

        # Default PIN code for incoming connections
        passkey "0000";

   # Default settings for HCI devices
device {
        # Local device name
        #   %d - device id
        #   %h - host name
        name "%h-%d";

        # Local device class
        # class 0x3e0100; #--host
        class 0x500204;

        # Default packet type
        #pkt_type DH1,DM1,HV1;

        # Inquiry and Page scan
        iscan enable; pscan enable;

        # Default link mode
        #   none   - no specific policy 
        #   accept - always accept incoming connections
        #   master - become master on incoming connections,
        #            deny role switch on outgoing connections
        lm accept;

        # Default link policy
        #   none    - no specific policy
        #   rswitch - allow role switch
        #   hold    - allow hold mode
        #   sniff   - allow sniff mode
        #   park    - allow park mode
        lp rswitch,hold,sniff,park;

And here is /etc/bluetooth/rfcomm.conf: (I added the device MAC and turned on automatic binding.. not sure if that was a good thing to do)

rfcomm0 {
        # Automatically bind the device at startup
        bind yes;

        # Bluetooth address of the device
        device 00:16:8F:BF:7B:E0;

        # RFCOMM channel for the connection
        channel 1;

        # Description of the connection
        comment "Example Bluetooth device";
  • Some googling eventually brought me to http://trifinite.org/trifinite_stuff_carwhisperer.html, which shows how to hijack weakly-protected car handsfree devices by simultaneously injecting and recording audio from a cars' HF. After more fiddling & looking at the supplied hcid.conf (which suggested the switch to cellphone device class as above) I got the aforementioned PIN window (in which 0000 was entered, as per the jabra PDF linked above), then by pressing the blinking blue button on the jabra at apparently the right time, I was able to send and record, though at a low quality and low rate - 8khz @ 8bits (?) = 64kbps? (the quality is perhaps lower than that..) This carwhisperer application doesn't work every time, but after '/etc/init.d/bluetooth restart' it usually functions.
  • Conclusions? I think it may work great for recording one or two neurons continuously, though this necessitates sorting the spikes on the headstage (through a filter & templates) and doing some filtering on the output to figure out what the noisy voice-encoded signal is trying to convey. Ideally, you could send just the timestamps over a RFCOMM link (this seems rather easy given what I've seen of the source of carwhisperer and given the copious details on the web for connecting Treos to linux laptops via RFCOMM DUNs (dial-up-networking), but who knows what the other (hardware) end looks like). Therefore, still need a blackfin-headstage (will work hard on this in NY!!) Also, the audio-output function of the jabra would be ideal for stimulation, or it could be disabled to save power.
  • Todo:
    1. buy another and see if i can record from 2 (or more!) simultaneously.
    2. get some low-power low-noise opamps and wire them to a omnetics to see if large neurons (e.g. channel 29) can be discriminated through a shitty bluetooth SCO link (well, at least it is low latency)
    3. see if a higher-quality bluetooth headset will work better (probably!)

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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: Francis-2005.11 tags: Joe_Francis motor_learning reaching humans delay intertrial interval date: 04-09-2007 22:48 gmt revision:1 [0] [head]

PMID-16132970[0] The Influence of the Inter-Reach-Interval on Motor Learning.

Previous studies have demonstrated changes in motor memories with the passage of time on the order of hours. We sought to further this work by determining the influence that time on the order of seconds has on motor learning by changing the duration between successive reaches (inter-reach-interval IRI). Human subjects made reaching movements to visual targets while holding onto a robotic manipulandum that presented a viscous curl field. We tested four experimental groups that differed with respect to the IRI (0.5, 5, 10 or 20 sec). The 0.5 sec IRI group performed significantly worse with respect to a learning index than the other groups over the first set of 192 reaches. Each group demonstrated significant learning during the first set. There was no significant difference with respect to the learning index between the 5, 10 or 20 sec IRI groups. During the second and third set of 192 reaches the 0.5 sec IRI group's performance became indistinguishable from the other groups indicating that fatigue did not cause the initial poor performance and that with continued training the initial deficit in performance could be overcome.


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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: Boline-2005.11 tags: electrophysiology motor cortex force isometric Ashe 2005 date: 04-09-2007 22:39 gmt revision:3 [2] [1] [0] [head]

this seems to be the same as {339}, with a different pubmed id & different author list. bug in the system!

PMID-16193273[0] On the relations between single cell activity in the motor cortex and the direction and magnitude of three-dimensional dynamic isometric force* the majority of cells responded to direction

  • few to the magnitude,
  • and ~10% to the direction & magnitude
  • control of static and dynamic motor systems is based on a common control process!
  • 2d task, monkeys, single-unit recording, regression analysis.


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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: bookmark-0 tags: FPGA verilog VHDL hacking hardware prototype date: 04-09-2007 22:34 gmt revision:2 [1] [0] [head]



http://www.ixo.de/info/usb_jtag/ open source USB Jtag adapter, works with dragon (I think!)

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ref: Sergio-2005.1 tags: isometric motor control kinematics kinetics Kalaska date: 04-09-2007 22:33 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

PMID-15888522[0] Motor cortex neural correlates of output kinematics and kinetics during isometric-force and arm-reaching tasks.

  • see [1]
  • recorded 132 units from the caudal M1
  • two tasks: isometric and movement of a heavy mass, both to 8 peripheral targets.
    • target location was digitized using a 'sonic digitizer'. trajectories look really good - the monkey was well trained.
  • idea: part of M1 functions near the output (of course)
    • evidence supporting this: M1 rasters during movement of the heavy mass show a triphasic profile: one to accelerate the mass, one to decelerate it, and another to hold it steady on target. see [2,3,4,5,6,7,8,9,10]


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ref: Hatsopoulos-2005.1 tags: motor control M1 Hatsopoulos date: 04-09-2007 22:26 gmt revision:1 [0] [head]

PMID-16160087[] Encoding in the Motor Cortex: Was Evarts Right After All? Focus on "Motor Cortex Neural Correlates of Output Kinematics and Kinetics During Isometric-Force and Arm-Reaching Tasks"

  • this is a discussion of the isometric vs. pendulum movement task. (and editorial focus)
    • in the isometric task, neurons are tuned to the direction of force, and fire anticipatorily.
    • in the movement task, they show a characteristic triphasic activity profile, very similar to what the muscles need.
  • neurons in the rostral bank of the CS seem to (almost) control muscle activation directly.
  • One possibility mentioned by the authors is that motor cortex may need to compensate for nonlinearities at the spinal motoneuron level as well as the low-pass filter characteristics of the muscles resulting in a nonlinear mapping between these neurons and the resulting forces at the hand.


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

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

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

Duke does not have online access to the article :(


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ref: Maier-1993.03 tags: force motor control grip electrophysiology date: 04-09-2007 20:20 gmt revision:4 [3] [2] [1] [0] [head]

PMID-8463818[0] Contribution of the monkey corticomotoneuronal system to the control of force in precision grip

  • recorded 33 corticomotoneronal cells
  • used spike-triggered averaging to find putative pyramidal tract neurons.
  • considerable trail-by-trial variability in the cells activity-force relationship
  • and, in an earlier work: PMID-810360[1] Relation of activity in precentral cortical neurons to force and rate of force change during isometric contractions of finger muscles.


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ref: HeppReymond-1999.09 tags: force motor control grip electrophysiology date: 04-09-2007 20:20 gmt revision:0 [head]

PMID-10473750[0] Context-dependent force coding in motor and premotor cortical areas.

  • here they found neurons related to dF/dt during another isometric precision grip task.


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ref: Caminiti-1991.05 tags: transform motor control M1 3D population_vector premotor Caminiti date: 04-09-2007 20:10 gmt revision:2 [1] [0] [head]

PMID-2027042[0] Making arm movements within different parts of space: the premotor and motor cortical representation of a coordinate system for reaching to visual targets.

  • trained monkeys to make similar movements in different parts of external/extrinsic 3D space.
  • change of preferred direction was graded in an orderly manner across extrinsic space.
  • virtually no correlations found to endpoint static position: "virtually all cells were related to the direction and not to the end point of movement" - compare to Graziano!
  • yet the population vector remained an accurate predictor of movement: "Unlike the individual cell preferred directions upon which they are based, movement population vectors did not change their spatial orientation across the work space, suggesting that they remain good predictors of movement direction regardless of the region of space in which movements are made"


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ref: Caminiti-1990.07 tags: transform motor control M1 3D population_vector premotor Caminiti date: 04-09-2007 20:07 gmt revision:4 [3] [2] [1] [0] [head]

PMID-2376768[0] Making arm movements within different parts of space: dynamic aspects in the primate motor cortex

  • monkeys made similar movements in different parts of external/extrinsic 3D space.
  • change of preferred direction was graded in an orderly manner across extrinsic space.
    • this change closely followed the changes in muscle activation required to effect the observed movements.
  • motor cortical cells can code direction of movement in a way which is dependent on the position of the arm in space
  • implies existence of mechanisms which facilitate the transformation between extrinsic (visual targets) and intrinsic coordinates
  • also see [1]


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ref: Kalaska-1989.06 tags: motor control direction tuning force Kalaska date: 04-09-2007 19:59 gmt revision:2 [1] [0] [head]

PMID-2723767[0] A comparison of movement direction-related versus load direction-related activity in primate motor cortex, using a two-dimensional reaching task.

  • comparison to georoplous task:
    • "We demonstrate here that many of these cells show similar large continuously graded changes in discharge when the monkey compensates for inertial loads which pull the arm in 8 different directions"
  • the mean activity of the sample population under any condition of movement direction and load direction can be described reasonably well by a simple linear summation of the movement-related discharge without any loads, and the change in tonic activity of the population caused by the load, measured prior to movement
  • their data support the dual kinematics/dynamics encoding in the motor cortex.
    • but, to me, the data also supports direct control of the muscles.


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ref: Georgopoulos-1992.06 tags: motor control force Georgopoulos date: 04-09-2007 19:56 gmt revision:1 [0] [head]

PMID-1609282[0] The motor cortex and the coding of force.

  • 2D isometric force, which dissociated force & changed in force.
  • cells are not tuned to the direction of the absolute force, but rather to the direction of both the visual cue and change in force (dF/dt) as measured using linear regressions in an isometric force task.


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ref: Wetts-1985.08 tags: Kalaska isometric motor control dentate cerebellum purkinje M1 pyramidal tract direction tuning date: 04-09-2007 19:54 gmt revision:0 [head]

PMID-3928831[0] Cerebellar nuclear cell activity during antagonist cocontraction and reciprocal inhibition of forearm muscles. by kalaska concering the interpositus dentate & isometric task.

  • the dentate nucleus sends afferents to the premotor areas. GABAergic inhibition from purkinje cells.
  • not so much tuning in the dentate nucleus as M1, but positive correlation was found.
  • Purkinje cells had a general low-order negative tuning to muscle activations.


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ref: Thach-1978.05 tags: monkeys motor control M1 cerebellum electropysiology date: 04-09-2007 19:53 gmt revision:3 [2] [1] [0] [head]

PMID-96223[0] Correlation of neural discharge with pattern and force of muscular activity, joint position, and direction of intended next movement in motor cortex and cerebellum.

  • recorded from M1 and interpositus/dentate nucleus of the cerebellum.
  • three classes of response in the interpositus/dentate and M1
    1. some in relation to the pattern of muscle activity
    2. some in relation to the position of the wrist
    3. some in relation to the next intended movement.


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

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

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


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ref: BrashersKrug-1996.07 tags: consolidation motor learning Shadmher Bizzi date: 04-09-2007 14:35 gmt revision:2 [1] [0] [head]

PMID-8717039[0] Consolidation in human motor memory

  • tested interference between the learning of two motor skills
    • no interference if the delay between practice on each task was > 4 hours
    • this implies that some memory consolodation occurs within those 4 hours.. the same as previous work which implicated the medial temporal lobe as an important region for memory encoding.
  • found with MIT open course ware -- there are a lot of good papers referenced there.


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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: Ashe-1997.09 tags: motor control force direction magnitude M1 cortex date: 04-09-2007 01:10 gmt revision:0 [head]

PMID-9331494[0] Force and the motor cortex.

  • most M1 cells seem to be related to the direction of static force; fewer related to direction and magnitude; fewer yet to only magnitude.
  • dynamic forces: there is a stron correlation between the rate of change of force and the motor cortex firing
    • dynamic force seems to determine firing rate moreso than static force (e.g. resisting gravity)
    • I have definantly seen evidence of this with the kinarm experiments.


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

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

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


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ref: Kettner-1988.08 tags: 3D motor control population_vector Schwartz Georgopoulos date: 04-05-2007 17:09 gmt revision:1 [0] [head]

A triptych of papers (good job increasing your publication count, guys!):

  • PMID-3411363[0] Primate motor cortex and free arm movements to visual targets in three-dimensional space. III. Positional gradients and population coding of movement direction from various movement origins.
    • propose multilinear model to predict firing rate of nneuron (a regression that is the same direction as the kalman filter)
    • i don't see how this is that much different from below (?)
  • PMID-3411362[1] Primate motor cortex and free arm movements to visual targets in three-dimensional space. II. Coding of the direction of movement by a neuronal population.
    • they show, basically, that they can predict movement direction (note this is different from actual movement!) using the poulation vector scheme.
  • PMID-3411361[2] Primate motor cortex and free arm movements to visual targets in three-dimensional space. I. Relations between single cell discharge and direction of movement.
    • 568 cells!!
    • 8 directional targets, again -- not sure how they were aranged; they say 'in approximately equal angular intervals'
    • these findings generalize the previous 2D results [3] (tuning to external space) to 3D


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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: Georgopoulos-1982.11 tags: georgopoulos kalaska caminiti M1 motor control tuning population_vector date: 04-05-2007 16:27 gmt revision:0 [head]

PMID-7143039[0] On the relations between the direction of two-dimensional arm movements and cell discharge in primate motor cortex

  • famous 8-target center out task
  • dot-product tuning
  • 75% of cells were found to be tuned.
  • posits the population code for directional movements - statistical summation & averaging, i presume.


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ref: Ostry-2003.12 tags: force motor control review cortex M1 date: 04-05-2007 15:21 gmt revision:0 [head]

PMID-14610628[0] A critical evaluation of the force control hypothesis in motor control.

  • the target of this review is the inverse dynamics model of motor control, which is very successful in robots. however, it seems that the mammalian nervous system does things a bit more complicated than this.
  • they agree that motor learning is most likely the defining feature of the cortex (i think that the critical and essential element of the cortex is not what control solution it arrives at, but rather how it learns that solution given the anatomical connections development has endowed it with.
  • they also find issue with the failure to incorporate realistic spinal reflexes into inverse-dynamics models.
  • However, we find little empirical evidence that specifically supports the inverse dynamics or forward internal model proposals per se.
  • We further conclude that the central idea of the force control hypothesis--that control levels operate through the central specification of forces--is flawed.


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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: Ferrari-2005.02 tags: tool use monkey neural response leaning mirror neurons F5 date: 04-03-2007 22:44 gmt revision:1 [0] [head]

PMID-15811234[] Mirror Neurons Responding to Observation of Actions Made with Tools in Monkey Ventral Premotor Cortex

  • respond when the monkey sees a human using a tool!


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ref: neuro-0 tags: spike sorting dendogram distance matrix Stapleton date: 04-02-2007 15:07 gmt revision:4 [3] [2] [1] [0] [head]

Friday March 30 Jen shared an interesting algorithm for spike sorting:

dist=pdist(psi); %This finds the Euclidean distances for all of the points (waveforms) in psi;
                  %dist is of the form of a row vector of length m(m-1)/2. Could convert into a 
                  %distance matrix via squareform function, but is computationally inefficient.
                  %m is the number of waveforms in psit.

link=linkage(dist); %This performs a nearest neighbor linkage on the distance matrix and returns
                    %a matrix of size (m-1)x3. Cols 1 and 2 contain the indices of the objects
                    %were linked in pairs to form a new cluster. This new cluster is assigned the 
                    %index value m+i. There are m-1 higher clusters that correspond to the interior
                    %nodes of the hierarchical cluster tree. Col 3 contains the corresponding linkage 
                    %distances between the objects paired in the clusters at each row i.

[H,T]=dendrogram(link,0); %This creates a dendrogram; 0 instructs the function to plot all nodes in 
                          %the tree. H is vector of line handles, and T a vector of the cluster 
                          %number assignment for each waveform in psit.

It looks real nice in theory, and computes very quickly on 2000 x 32 waveform data (provided you don't want to plot) -- however, I'm not sure if it works properly on synthetic data. Here are the commands that i tried:

v = [randn(1000, 32); (randn(1000, 32) + rvecrep(ones(1,32),1000))];
[coef, vec] = pca(v);
vv = v * vec(:, 1:2);
dist = pdist(vv);
link = linkage(dist);
DensityPlotOpenGL(vv(:,1), vv(:,2))

-- the fitted dendogram, without PCA

-- the fitted dendogram, with PCA

-- the asociated PCA plot of the data, clearly showing two clusters.

need to figure out how jen made the colorized plots

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

we are proud of this :)

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ref: AnguianoRodrAguez-2007.02 tags: serotonin learning dopamine date: 03-12-2007 02:30 gmt revision:0 [head]

PMID-17126827 Striatal serotonin depletion facilitates rat egocentric learning via dopamine modulation. facilitates - they get better! (more awake than controls? inability to forget?)

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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: Dum-2003.01 tags: cerebellum dentate_nucleus projections cerebrum prefrontal posterior_pareital M1 PM thalamus somatotopic date: 03-11-2007 04:42 gmt revision:2 [1] [0] [head]

PMID-12522208 An unfolded map of the cerebellar dentate nucleus and its projections to the cerebral cortex

  • the dentate nucleus of the cerebellum projects to (at least four sections of if not all) of the cerebral cortex in a spatially-organized way.
    • dentate nucleus projects via the ventral anterior (VA) nucleus of the thalamus
    • dentate nucleus receives projections from the lateral hemispheres of the cerebellum (neocerebellum), which receives extensive collaterals from the pyramidal tract.

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


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

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ref: notes-0 tags: patents USPTO date: 02-22-2007 04:28 gmt revision:0 [head]

http://0-www.uspto.gov.mill1.sjlibrary.org/web/offices/com/iip/transcriptsf_m.htm -- great FAQ

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

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

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

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

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



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ref: Brockwell-2004.04 tags: particle_filter Brockwell BMI 2004 wiener filter population_vector MCMC date: 02-05-2007 18:54 gmt revision:1 [0] [head]

PMID-15010499[0] Recursive Bayesian Decoding of Motor Cortical Signals by Particle Filtering

  • It seems that particle filtering is 3-5 times more efficient / accurate than optimal linear control, and 7-10 times more efficient than the population vector method.
  • synthetic data: inhomogeneous poisson point process, 400 bins of 30ms width = 12 seconds, random walk model.
  • monkey data: 258 neurons recorded in independent experiments in the ventral premotor cortex. monkey performed a 3D center-out task followed by an ellipse tracing task.
  • Bayesian methods work optimally when their models/assumptions hold for the data being analyzed.
  • Bayesian filters in the past were computationally inefficient; particle filtering was developed as a method to address this problem.
  • tested the particle filter in a simulated study and a single-unit monkey recording ellipse-tracing experiment. (data from Rena and Schwartz 2003)
  • there is a lot of math in the latter half of the paper describing their results. The tracings look really good, and I guess this is from the quality of the single-unit recordings.
  • appendix details the 'innovative methodology ;)


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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: machine_learning todorov motor_control date: 0-0-2007 0:0 revision:0 [head]

Iterative Linear Quadratic regulator design for nonlinear biological movement systems

  • paper for an international conference on informatics in control/automation/robotics

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ref: bookmark-0 tags: metal_halide projector light CRI Venture Osram Phillips date: 0-0-2007 0:0 revision:0 [head]

Overview: a projector light should have good luminous efficiency, have a long life, and most importantly have plenty of energy in the red region of the spectrum. most metal halides have yellow/green lines and blue lines, few have good red lines.

http://www.osram.no/brosjyrer/english/K01KAP5_en.pdf in 1000 watt, the Osram Powerstar HQI-TS 1000/d/s looks the best: CRI > 90, 5900K color temperature. Unfortunately, I cannot seem to find any american places to buy this bulb, nor can i determine its average life. It can be bought, at a price, from http://www.svetila.com/eProdaja/product_info.php/products_id/442 { n.b. the osram HMI bulbs are no good-the lifetime is too short}

In 400 watt, the Eye Clean Arc MT400D/BUD looks quite good, with a CRI of 90, 6500K color temp. http://www.eyelighting.com/cleanarc.html. EYE also has a ceraarc line, but the 400w bulb is not yet in production (and it has a lower color temperature, 4000K). Can be bought from http://www.businesslights.com/ (N.B. they have spectral charts for many of the lights!)

  • I've also seen reference to the Phillips mastercolor line: http://www.nam.lighting.philips.com/us/ecatalog/hid/pdf/p-5497c.pdf
    • these are ceramic HPS white replacements ('retro-white'). 85CRI, 4000K color temperature, reasonably efficient over the life of the bulb.
  • Ushio
  • Venture lighting has a 400W naturalWhite e-lamp (5000k, 90+ CRI). For use with both pulse-start and the electronic ballasts that they sell.

and fYI, the electrodelass bulbs are made by Osram and are called "ICETRON". They are rather expensive, but last 1e5 hours (!). Typical output is 80 lumens/watt

more things of interest:

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ref: bookmark-0 tags: Shadmehr torque forces jacobian date: 0-0-2007 0:0 revision:0 [head]

The Computational Neurobiology of Reaching and Pointing - online notes

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ref: bookmark-0 tags: motor learning control Wolpert Ghahramani date: 0-0-2007 0:0 revision:0 [head]


  • the curse of dimensionality: there are about 600 muscles in the human body; 2^600 >> than the # of atoms in the universe! we must structure this control problem.
  • there are about 200,000 alpha motor neurons.
  • damage to parietal cortex can lead to an inability to maintain state estimates of the limb (and other objects?)
  • damage to pareital cortex can lead to and inability to mentally simulate movement with the affected hand.
  • damage to the left pareital cortex can lead to a relative inability to determine wheither viewed movements are ones own or not.
  • state prediction can reduce the effect of delays in sensorimotor feedback loops.
    • example: soleus and gastrocinemus tightent before lifting a heavy load with the arms.
  • the primate CNS models both the expected sensory feedback and represents the likelihood of the sensory feedback given the context. e.g. if people think that they are moving, they will compensate for non-existent coriolis forces.
  • ''how are we able to learn a variety of contexts?
    • when subjects try to learn two different dynamics (e.g. forward and reverse on sideskates), interference occurs when they are presented in rapid sucession, but not when they are separated by several hours.)
  • has a good list of refs.

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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: learning-0 tags: motor control primitives nonlinear feedback systems optimization date: 0-0-2007 0:0 revision:0 [head]

http://hardm.ath.cx:88/pdf/Schaal2003_LearningMotor.pdf not in pubmed.

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ref: Schaal-2005.12 tags: schaal motor learning review date: 0-0-2007 0:0 revision:0 [head]

PMID-16271466 Computational Motor control in humans and robots

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ref: Blankertz-2006.06 tags: BMI EEG ECoG competiton 2006 date: 0-0-2007 0:0 revision:0 [head]

PMID-16792282 http://hardm.ath.cx:88/pdf/BCIcompetition2006.pdf

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ref: van-2004.11 tags: anterior cingulate cortex error performance monitoring 2004 date: 0-0-2007 0:0 revision:0 [head]

PMID-15518940 Errors without conflict: implications for performance monitoring theories of anterior cingulate cortex.

  • did a event-locked fMRI to study whether the ACC would differentiate between correct and incorrect feedback stimuli in a time estimation task.
  • ACC seems to be not involved in error detection, just conflict.
  • according to one theory, ERN is generated as part of a reinforcement learning process. (Holroyd and Coles 2002): behavior is monitored by an 'adaptive critic' in the basal ganglia.
    • in this theory, the ACC is used to select between mental processes competing to access the motor system.
    • ERN corresponds to a decrease in dopamine.
    • ERN occurs when the stimulus indicates that an error has occured.
  • alternately, the ACC can monitor for the presence of conflict between simultaneously active but incompatible sensory/processing streams.
    • the ACC is active in correct trials in tasks that require conflict resolution. + it makes sense from a modeling strategy: high-energy state is equivalent to a state of conflit: many neurons are active at the same time.
    • that is, it is a stimuli resolver: e.g. the stroop task.
  • some studies localize (and the authors here indicate that the source-analysis that localizes dipole sources is inaccurate) the error potential to the posterior cingulate cortex.
    • fMRI solves this problem.
  • from their figures, it seems that the right putamen + bilateral caudate are involved in their time-estimation task (subjects has to press a button 1 second after a stimulus cue; feedback then guided/misguided them toward/away from 1000ms; subjects, of course, adjusted their behavior)
    • no sign of ACC activation was shown - as hard as they could look - despite identical (more or less) experimental design to the ERN studies.
      • hence, ERN is generated by areas other than the ACC.
  • in contrast, the stroop task fully engaged the anterior cingulate cortex.
  • cool: perhaps, then, error feedback negativity is better conceived as an (absence of) superimposed "correct feedback positivity" 'cause no area was more active in error than correct feedback.
  • of course, one is measuring brain activation through blood flow, and the other is measuring EEG signals.

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ref: Blankertz-2003.06 tags: BMI BCI EEG error classification motor commands Blankertz date: 0-0-2007 0:0 revision:0 [head]

PMID-12899253 Boosting bit rates and error detection for the classification of fast-paced motor commands based on single-trial EEG analysis

  • want to minimize subject training and maximize the major learning load on the computer.
  • task: predict the laterality of imminent left-right hand finger movements in a natural keyboard typing condition. they got ~15bits/minute (in one subject, ~50bits per minute!)
    • used non-oscilatory signals.
  • did a to detect 85% percent of error trials, and limited false-positives to ~2%

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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: Stefani-1995.09 tags: electrophysiology dopamine basal_ganglia motor learning date: 0-0-2007 0:0 revision:0 [head]

PMID-8539419 Electrophysiology of dopamine D-1 receptors in the basal ganglia: old facts and new perspectives.

  • D1 is inhibitory (modulatory) on striatal neurons.
  • D1 cloned in 1990
  • D1 stimulates adenyl cyclase. (cAMP)
  • D1 activity shown to be necessary, but not sufficient, to generate long-term depression in striatal slices.
  • SKF 38393 was designed as a selective D1 receptor agonist; it has been available since the late 70's; it has nanomolar affinity for D1-R. SKF 38393 inhibits action potential discharge in striatal neurons as measued through response to intracellular current depolarizations.
  • striatal cells project to the substantia nigra.
  • alternate hypothesis: D1 activation on the striatonigral afferents to the ventral tegmental area (VTA) promotes GABA release.
    • recall that the VTA projects to the frontal/prefrontal cortex (PFC) via the mesocortical dopiminergic pathway. http://grad.uchc.edu/phdfaculty/antic.html There, DA synapese on spines of distal dendrites in juxtaposition with glutamergic synapses. this guy posits that these DA synapses are involved in the pathology of schizophrenia, and he uses optical techniques to measure the DA/Glu synapses.
    • VTA is just below the red nucleus in rats.
  • some people report that SKF 38393 potentiated depolarizing membrane responses to exogenous NMDA (agonist, excitotoxin).
  • they prefer the magnesium-dependent LTD pathway.
    • D1 receptor antagonist SCH 23390 prevented the generation of LTD in striatum. (Calabresi et al 1992).
    • in DA-depleted slices, LTD could be restored by the co-administration of D1 and D2 agonists.

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ref: Harris-1998.08 tags: motor_control error variance optimal_control 1998 wolpert date: 0-0-2007 0:0 revision:0 [head]

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

  • key idea: neural control signals are corrupted by noise whose variance increases with the size of the control signal
  • this idea is sufficient to explain a number of features of human motor behavior.


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ref: neuro notes-0 tags: Dopamine receptor D1 D2 date: 0-0-2007 0:0 revision:0 [head]


  • the D1 receptor is coupled to stimulatory G-proteins, which cause cell depolarization. (pathway: stimulatory g-protein -> actibation of adenylate cyclase converts ATP -> cAMP -> PKC -> phosphorylation of sodium (and calcium?) channel.
  • the D2 receptor (family?) is coupled to inhibitory G-proteins, which decrease the activity of adenylate cyclase. this is a pretty vague picture.

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ref: bookmark-0 tags: graffiti art urban photography date: 0-0-2006 0:0 revision:0 [head]

http://www.beautifulcrime.com/public/exhibitions/ Need flash to view the site.

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ref: bookmark-0 tags: urban art san_francisco california vector_art mod_art store date: 0-0-2006 0:0 revision:0 [head]


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ref: bookmark-0 tags: pythong c howto date: 0-0-2006 0:0 revision:0 [head]


here you go timmyh, enjoy..


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

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

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


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

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ref: bookmark-0 tags: smith predictor motor control wolpert cerebellum machine_learning prediction date: 0-0-2006 0:0 revision:0 [head]


  • quote in reference to models in which the cerebellum works as a smith predictor, e.g. feedforward prediction of the behavior of the limbs, eyes, trunk: Motor performance based on the use of such internal models would be degraded if the model was inavailable or inaccurate. These theories could therefore account for dysmetria, tremor, and dyssynergia, and perhaps also for increased reaction times.
  • note the difference between inverse model (transforms end target to a motor plan) and inverse models 9is used on-line in a tight feedback loop).
  • The difficulty becomes one of detecting mismatches between a rapid prediction of the outcome of a movement and the real feedback that arrives later in time (duh! :)
  • good set of notes on simple simulated smith predictor performance.

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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: bookmark-0 tags: poisson tutorial ISI date: 0-0-2006 0:0 revision:0 [head]

http://www.neuroscience.ucsf.edu/neurograd/courses/ns201b_2004/Miller/03-12-04_PoissonProcess.pdf http://robotics.caltech.edu/~zoran/Research/poisson/node1.html

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ref: bookmark-0 tags: perl regular expressions tutorial regex date: 0-0-2006 0:0 revision:0 [head]