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

[0] Allman JM, Hakeem A, Erwin JM, Nimchinsky E, Hof P, The anterior cingulate cortex. The evolution of an interface between emotion and cognition.Ann N Y Acad Sci 935no Issue 107-17 (2001 May)

[0] Schultz W, Multiple reward signals in the brain.Nat Rev Neurosci 1:3, 199-207 (2000 Dec)[1] Schultz W, Tremblay L, Hollerman JR, Reward processing in primate orbitofrontal cortex and basal ganglia.Cereb Cortex 10:3, 272-84 (2000 Mar)

[0] Schultz W, Tremblay L, Hollerman JR, Reward processing in primate orbitofrontal cortex and basal ganglia.Cereb Cortex 10:3, 272-84 (2000 Mar)

[0] Buonomano DV, Merzenich MM, Cortical plasticity: from synapses to maps.Annu Rev Neurosci 21no Issue 149-86 (1998)

[0] Hikosaka O, Nakamura K, Sakai K, Nakahara H, Central mechanisms of motor skill learning.Curr Opin Neurobiol 12:2, 217-22 (2002 Apr)

[0] Fregni F, Simon DK, Wu A, Pascual-Leone A, Non-invasive brain stimulation for Parkinson's disease: a systematic review and meta-analysis of the literature.J Neurol Neurosurg Psychiatry 76:12, 1614-23 (2005 Dec)[1] Lefaucheur JP, Drouot X, Von Raison F, Menard-Lefaucheur I, Cesaro P, Nguyen JP, Improvement of motor performance and modulation of cortical excitability by repetitive transcranial magnetic stimulation of the motor cortex in Parkinson's disease.Clin Neurophysiol 115:11, 2530-41 (2004 Nov)[2] Mally J, Stone TW, New advances in the rehabilitation of CNS diseases applying rTMS.Expert Rev Neurother 7:2, 165-77 (2007 Feb)[3] Khedr EM, Rothwell JC, Shawky OA, Ahmed MA, Hamdy A, Effect of daily repetitive transcranial magnetic stimulation on motor performance in Parkinson's disease.Mov Disord 21:12, 2201-5 (2006 Dec)[4] Brusa L, Versace V, Koch G, Iani C, Stanzione P, Bernardi G, Centonze D, Low frequency rTMS of the SMA transiently ameliorates peak-dose LID in Parkinson's disease.Clin Neurophysiol 117:9, 1917-21 (2006 Sep)[5] Strafella AP, Ko JH, Monchi O, Therapeutic application of transcranial magnetic stimulation in Parkinson's disease: the contribution of expectation.Neuroimage 31:4, 1666-72 (2006 Jul 15)

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

[0] Birbaumer N, Cohen LG, Brain-computer interfaces: communication and restoration of movement in paralysis.J Physiol 579:Pt 3, 621-36 (2007 Mar 15)

[0] Schwartz AB, Cortical neural prosthetics.Annu Rev Neurosci 27no Issue 487-507 (2004)[1] Carmena JM, Lebedev MA, Henriquez CS, Nicolelis MA, Stable ensemble performance with single-neuron variability during reaching movements in primates.J Neurosci 25:46, 10712-6 (2005 Nov 16)

[0] Ostry DJ, Feldman AG, A critical evaluation of the force control hypothesis in motor control.Exp Brain Res 153:3, 275-88 (2003 Dec)

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

Quick review of electrode area / impedance within m8ta:

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

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

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

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

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ref: -0 tags: Leiber nanoFET review silicon neural recording intracellular date: 02-01-2017 03:32 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-23451719 Synthetic Nanoelectronic Probes for Biological Cells and Tissue

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

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

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

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

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

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

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

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

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

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

____References____

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

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

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

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

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

PLoS One:

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

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

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

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

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

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

PMID-23408972 Credit Assignment during Movement Reinforcement Learning

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

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

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

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

  • unimanual / bimanual tasks.

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

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

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

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

Journal of Neural Engineering:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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


Nature Methods:

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

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

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

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

Nanowires, useful for Flip's idea.

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


Of personal interest:

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

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

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

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

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

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

  • Debatable causality.

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

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

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

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

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

  • Light and voltage controlled memsistors. Interesting.

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

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

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

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

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

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

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ref: -0 tags: 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: -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: Mink-1996.11 tags: basal ganglia review parkinsons STN DBS date: 03-05-2012 23:33 gmt revision:13 [12] [11] [10] [9] [8] [7] [head]

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

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

Electrophysiology:

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

STN:

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

GPi:

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

SNr:

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

GPe:

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

SNpc:

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

Synthesis:

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

Parkinson's disease:

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

Huntingtons

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

STN / Hemiballismus

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

Experimental lesions:

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

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

____References____

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

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ref: Weinberger-2009.09 tags: STN DBS PD oscillations beta band review date: 03-05-2012 16:32 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-19460368[0] Pathological subthalamic nucleus oscillations in PD: can they be the cause of bradykinesia and akinesia?

  • Review of {1075}
  • Suppression of beta-band is correlated with the improvement in combined measures of bradykinesia and rigidity.
    • This does not mean that the oscillations cause rigidity! only that L-DOPA affects both. Focused entirely on Beta band.
  • Previously shown that the degree of beta oscillatory activity in the STN of PD patients correlates with the patients' benefit from dopaminergic medications, but not with baseline motor deficits. (the treatment but not the symptoms)
  • Levy 2000, 2001 for the existence of oscillatory activity in the STN & globus pallidus.
  • Prominent beta band activity in GPi & STN LFP. [Levy 2000, Levy 2001 , Brown 2001]
  • Short train HFS of the STN has been shown to decrease STN-cortex coherence for up to 25s after application. [Wingeier 2006] [Kuhn 2008]
    • Others disagree. [Foffani et al., 2006] and [Rossi et al., 2008] ).
  • In a response task, decrease in beta-band activity negatively correlates with reaction time. [Kuhn 2004]
    • Beta suppression is also correlated with increased motor planning [Williams 2005]
  • Beta band activity also present in healthy monkey striatum, human putamen, and cortex. (I wonder how? many references.)
  • Yet, to date there is no clear evidence that the degree of synchronization in the beta band directly accounts for the motor deficits in PD.
  • It has been recently shown that the percentage of neurons exhibiting oscillatory firing in the beta range correlates well (r squared = 0.62) with the degree by which PD motor symptoms improved after dopamine replacement therapy (Weinberger et al. 2006 PMID-17005611)
  • It should be noted that decrease in beta-band activity may be caused by -- rather than causal of -- decreased akinesia and rigidity.
    • That said, in rats treated with 6-OHDA, an increase in beta band activity took several days to appear after drug administration, and appeared at the same time as clinical symptoms.
  • Interesting! Activity-dependent plasticity was remarkably enhanced with a low dose of levodopa in the basal ganglia output of SNr and that there was a surprisingly good correlation (r squared = 0.81) between symptoms and the level of synaptic plasticity (Prescott et al., 2009) [2].
  • Other theory: exaggerated synchrony in the basal ganglia limits the ability to encode meaningful information, as all neurons are entrained to the same frequency hence undifferentiated.
    • Thought beta band may just be a non-coding resting state. Synaptic plasticity goes awry, and all neurons become entrained. Explains bradykinesia but not rigidity.

____References____

[0] Weinberger M, Hutchison WD, Dostrovsky JO, Pathological subthalamic nucleus oscillations in PD: can they be the cause of bradykinesia and akinesia?Exp Neurol 219:1, 58-61 (2009 Sep)
[1] Kühn AA, Tsui A, Aziz T, Ray N, Brücke C, Kupsch A, Schneider GH, Brown P, Pathological synchronisation in the subthalamic nucleus of patients with Parkinson's disease relates to both bradykinesia and rigidity.Exp Neurol 215:2, 380-7 (2009 Feb)
[2] Prescott IA, Dostrovsky JO, Moro E, Hodaie M, Lozano AM, Hutchison WD, Levodopa enhances synaptic plasticity in the substantia nigra pars reticulata of Parkinson's disease patients.Brain 132:Pt 2, 309-18 (2009 Feb)

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ref: Penney-1983.01 tags: DBS parkinsons model review chorea review date: 03-02-2012 21:22 gmt revision:2 [1] [0] [head]

PMID-6838141[0] Speculations on the Functional Anatomy of Basal Ganglia Disorders

  • "We present a model based on the accumulating evidence that suggests the importance of a cortico-striato-pallido-thalamocortical feedback circuit as the major extrapyramidal influcence on the motor system in man.
    • Behaviors generated from the cerebral cortex are focused and facilitated by projections through the basal ganglia.
    • The chorea of Huntington's disease and the bradykineasia of PD are opposite extremes of the dysfunction of this system.
      • Huntington's: inability to supress unwanted movements.
      • Inadequate inhibitory modulation of ongoing movement by the nigrostriatal dopamine pathway.
  • Anatomy already described in Kemp & Powell 1971. More details have accrued in the subsequent 4 decades.
  • Kinner Wilson 1929 -- astute observations on the nature of chorea, in Huntington's and others: how they appear to be purposeful, but are objectviely not. He infers that it may be a disorder of the premotor cortex, since the primary cortex seems to control individual muscle contractions. Much data supports this now.
  • All dopamine agonists result in choreiform dyskinesias.
  • Tardive dyskinesia seems to result from drug-induced striatal dopamine receptor supersensitivity after long-term high-dose neuroleptic therapy also manifests choreaform movements.
  • In huntington's disease, supersensitive GABA receptors develop in the globus pallidus following striatal deinnervation.
    • Likewise for PD: supersensitive dopamine receptors develop in the striatum (Lee at al 1978).
  • mention neuromodulators (substance P, angiotensin II, cholecystokinin, leucine-enkephalin) which have been largely ignored in later work -- why?
  • Tremor is very responsive to muscarinic cholinergic agonists, hence striatal cholinergic neurons may play a role in the etiology of tremor.
    • Or the effect could be mediated through the cortex (my observation).
    • But then again this is inconsistent with the fact that pallidotomy is effective at mediating tremor in PD patients.
    • Tremor is unusual in diseases like Hallervorden-Spatz and other pallidal degenerations presumably because pallidothalamic pathways are necessary for the manifestation of PD tremor.
  • THe descending SNr pathways to the tectum and midbrain tegmentum appear to be responsible for the rotatory behavior seen in models of parkinsonism in the rat (Morelli et al 1981).
    • Rotatory behavior exhibited by rats after lesioning of nigral dopamine neurons continues even in the absence of the telencephalon and thalamus (Papadopolous and Huston 1981).

Got some things completely wrong:

  • Say that the cells of the subthalamic nucleus are inhibitory on the cells of MGP (GPi)/SNr

____References____

[0] Penney JB Jr, Young AB, Speculations on the functional anatomy of basal ganglia disorders.Annu Rev Neurosci 6no Issue 73-94 (1983)

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

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

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

____References____

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

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

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

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

____References____

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

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

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

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

____References____

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

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ref: 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.

____References____

[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.

____References____

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

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ref: Israel-2008.01 tags: review DBS caudate putamen STN date: 01-25-2012 00:56 gmt revision:3 [2] [1] [0] [head]

PMID-17949812[0] Pathophysiology of the basal ganglia and movement disorders: From animal models to human clinical applications

  • MPTP monkeys:
    • resting tremor is not easily repeated in MPTP treated macaque monkeys, though it does occur in green (vervet) monkeys.
    • low doses of MPTP seem to first cause mild frontal cognitive deficits in monkeys without motor signs. (strange...); this acute MPTP treatment produced DA depletion that is equal or more severe in the caudate nucleus than in the putamen.
    • in comparison, lower, longer doses of the toxin, which is thought to better emulate the progression of PD, causes a greater decrease in the putamen.
    • frontal eye effects and cognitive deficits are observed before motor signs, which is in line with early cog. deficits found in human MPTP and PD.
    • MPTP treatment results in an increase in the number of neurons that fire in bursts.
    • physiological studies of the pallidum in MPTP-treated monkeys demonstrate that their pair-wise crosscorrelograms become peaked and oscillatory, suggesting that DA depletion induces an abnormal coupling of basal ganglia loops (could test this in my data).
  • tonic firing rate of STN neurons is (they claim) about 20Hz; this increases to about 25Hz after MPTP treatment. The firing rate of neurons in the GPi increase with MPTP, GPE decrease.
  • their description of the ''box and arrow' model of pathophysiology of PD is quite easy to understand, as are their critiques - that it fails to explain the dynamic manifestations of the disease, namely resting tremor and rigidity.
  • there are hyper-direct projections from the motor cortex to the STN
  • the box and arrow model does not accurately predict the result of removal of GPi: according to the direct/indirect pathway model, removal of the GPI should alleviate akinesia, bradykinesia, and rigidity. However, pallidotomy has been shown to be primarily effective in alleviating l-dopa induced dyskinesias (involuntary movements, like tic or chorea) -- exactly the opposite of what the model would predict.
  • a better (or at least more recent) model is that the striatum / pallidus / STN are involved in selection of actions & inhibition of competing actions; this is achieved via focused striatial inhibition.
    • problem: changes in pallidal activity lag behind movement initiation (!)
  • even better hypothesis: that the basal ganglia perform reinforcement driven dimensionality reduction. This has been discussed by Graybeil and others, but it's implication to PD is only lightly touched here (they mention that it is more in accord with neurons in the striatum involved in the same actions to no show an increase in correlation as would be expected from an action-selection hypothesis.
  • remind us that exposed-metal microelectrodes have a tendency to stimulate fibers, not cell bodies.
    • nevertheless, the effect of DBS in PD is remarkably similar to lesion; the exact mechanism is still under intense study. (hypotheses: depolarization block, stimulation of bypassing inhibitory pathways, induction of GABA release from GPe projection neurons. )
    • their hypothesis: DBS enforces a constant spatio-temporal firing pattern of the discharge structures of the basal ganglia. The null output of the globus pallidus is ignored by the rich thalamic & cortical circuits, which can 'take over'.
  • ( in the conclusion: quote: "These findings may call for development of future therapies that will target this abnormal synchronization (Tass, 1999 P.A. Tass, Phase Resetting in Medicine and Biology, Springer, Berlin (1999).Tass, 1999)." exactly!!

____References____

[0] Israel Z, Bergman H, Pathophysiology of the basal ganglia and movement disorders: from animal models to human clinical applications.Neurosci Biobehav Rev 32:3, 367-77 (2008)

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

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

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

____References____

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

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

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

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

____References____

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

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ref: Fetz-2000.12 tags: motor control spinal neurons interneurons movement primitives Fetz review tuning date: 01-03-2012 23:08 gmt revision:4 [3] [2] [1] [0] [head]

PMID-11240278[0] Functions of mammalian spinal interneurons during movement

  • this issue of current opinion in neuro has many reviews of motor control
  • points out that the Bizzi results (they microstimulated & observed a force-field-primitive type organization)
    • others have found that this may be a consequence of decerebration + the structure of the biomechanical groupings of muscles. (see 'update').
  • intraspinal electrodes in the cat provide a secure and reliable method of eliciting forces and movements.
  • CM (corticomotor) cells more often represent synergistic groups of muscles, whereas premotor spinal interneurons are organized to target specific muscles.
    • CMs are therefore more strictly recruited for particular movements.
  • interneurons (IN) are, of course, arrayed in such a way so that antagonist and agonist muscles cross-inhibit eachother (for efficiency)
    • however, we are still able to control the endpoint impedance of the arm - how?
  • spinal interneurons modulate activity during wait period prior to movement!
    • there might be substantial interaction between the cortex and spinal cord.. subjects asked to imagine pressing a foot pedal showed enhanced reflexes in the involved soleus muscle.
      • cognitive priming?
  • spinal reflexes are strongly modulated in movement.

____References____

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ref: Lebedev-2006.09 tags: misha lebedev nicolelis BMI past present future electrodes review MEA date: 01-03-2012 03:26 gmt revision:2 [1] [0] [head]

PMID-16859758 Brain-machine interfaces: past, present and future.

  • Describes the state of the art & what needs to be done. Namely, better recording quality.
  • state that current EEG BMIs are limited to 5-25 bits/min (typo!!) [2,11]
    • [2] Wolpaw "Brain-computer interfaces for communication and control" 2002.
    • [11] Birbaumer "Brain-computer-interface research: coming of age" 2006.
  • set of references on biofeedback control of EEG in research animals.
  • EEG BCIs are either biofeedback based or classifier (P300, synchronous decoder ) based.
  • First invasive BMIs Fetz [40-45], Schmidt [46]; progress has been limited by technology. Must have been quite challenging for him to do the research!
    • [40] Fetz "Operant Conditioning of cortical unit activity" 1969
    • [41] Fetz "Are movement parameters recognizably coded in activity of single neurons?" 1992
    • [42] Fetz and Baker "Operantly conditioned patterns on precentral unit activity and correlated responses in adjacent cells and contralateral muscles." 1973
    • [43] Fetz and Finocchio "Operant Conditioning of specific patterns of neural and muscular activity" 1971
    • [44] Fetz and Finocchio "Operant conditioning of isolated activity in specific muscles and precentral cells" 1972
    • [45] Fetz and Finocchio 1975 "Correlations between activity of motor cortex cells and arm muscles during operantly conditioned response patterns." 1975
    • [46] Schmidt "single neuron recording from motor cortex as a possible source of signals for control of external devices." 1980
  • microelectrode arrays solved one of the problems.
  • talk about how more neurons are needed.
  • Principles of BMIs: Evarts [66-68], neuronal modulations are highly variable [69-72].
    • [66] Evarts, E.V. (1966) Pyramidal tract activity associated with a conditioned hand movement in the monkey.
    • [67] Evarts, E.V. (1968) Relation of pyramidal tract activity to force exerted during voluntary movement.
    • [68] Evarts, E.V. (1968) A technique for recording activity of subcortical neurons in moving animals.
    • "THus, as much as neighboring neurons might display highly disinct firing modulation patterns during the execution of a particular movement, single-neuron firing can vary substantially from one trial to the next, despite the fact that the overt movements remain virtually identical. :
    • "averaging across large populations of neurons significantly reduces the variability of signals derived from single neurons [54, 69].
    • Should i mention this in thesis?
  • Better way to assimilate the BMI into the body is to have proprioceptive feedback.
  • suggest the same standard things to be improved, excluding electronics. :
    • electrodes / recording
    • decoding
    • incorporating plasticity
    • better prosthetics.
  • "multi-unit signals can also be efficiently used in BMI control [57] {318}.
  • Some groups have strongly claimed that recordings from a small number of neurons can be sufficient for good performance in a BMI. [55,56,63]
    • This is not Miguel's approach: more neurons confers accuracy [54{317},57,70] and reliability [69].
      • [70] Wessberg, J. and Nicolelis, M.A. (2004) Optimizing a linear algorithm for real-time robotic control using chronic cortical ensemble recordings in monkeys. J. Cogn. Neurosci. 16, 1022–1035
  • Still need new microelectrodes; electrodes become encapsulated by fibrous tissue and cells die in the vicinity of electrodes [77] {781}.
    • suggest anti-inflammatory coating, though the jury is out.
  • Initial wireless telemetry systems: [93-99]. [93]{315}
    • [94] Knutti, J.W. et al. (1979) An integrated circuit approach to totally implantable telemetry systems. Biotelem. Patient Monit. 6, 95–106
    • [97] Chien, C.N. and Jaw, F.S. (2005) Miniature telemetry system for the recording of action and field potentials. J. Neurosci. Methods 147
    • [98] {930}
    • [99] Morizio Morizio, J. et al. (2005) Fifteen-channel wireless headstage system for single-unit rat recordings.
    • [100] (of broader interest) Moxon, K.A. et al. (2004) Ceramic-based multisite electrode arrays for chronic single-neuron recording. IEEE Trans. Biomed. Eng. 51, 647–656
  • nanotechnology probes that access the brain through the vasular system [101].
  • although a good number of linear and nonlinear algorithms have been proposed and tested [1,54,56,57,70,110-116], Wiener filters have proved sufficient [54,55,57,58,65,117].
  • almost 140 years ago Head and Holmes suggested that the body schema -- that is, the internal brain representation of one's body -- could extend itself to include a wielded tool.

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ref: Shulgina-1986.09 tags: reinforcement learning review date: 01-03-2012 02:31 gmt revision:5 [4] [3] [2] [1] [0] [head]

Reinforcement learning in the cortex (a web scour/crawl):

  • http://www.springerlink.com/content/v211201413228x34/
    • short/long interspike intervals via pain reinforcement in immobilized rabbits.
  • PMID-3748636 Increased regularity of activity of cortical neurons in learning due to disinhibitory effect of reinforcement.
    • more rabbit shocking.
  • http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T0F-3S1PT00-P
    • applied glutamate & noradrenaline; both responses are complex.
  • Reinforcement learning in populations of spiking neurons
    • the result: reinforcement learning can function effectively in large populations of neurons if there is a trace of the population activity in addition to the reinforcement signal. this trace must be per-synapes or perhaps per-neuron (as has been anticipated for some time). very important result, helps with the 'specificity' problem.
    • in human terms, the standard reinforcement learning approach is analogous to having a class of students write an exam and being informed by the teacher on the next day whether the majority of students passed or not.
    • this learning method is slow and achieves limited fidelity; in contrast, behavioral reinforcement learning can be reliable and fast. (perhaps this is a result of already-existing maps and or activity in the cortex?)
    • reinforcement learning is almost the opposite of backpropagation, in that in backprop, a error signal is computed per neuron, while in reinforcement learning the error is only computed for the entire system. They posit that there must be a middle ground (need something less than one neuron to compute the training/error signal per neuron, othewise the system would not be very efficient...)
    • points out a good if obvious point: to learn from trial and error different responses to a given stimulus must be explored, and, for this, randomness in the neural activities provides a convenient mechanism.
    • they use the running mean as an eligibility trace per synapse. then change in weight = eta * eligibility trace(t), evaluated at the ends of trials.
    • implemented an asymmetric rule that updates the synapses only slightly if the output is reliable and correct.
    • also needed a population signal or fed-back version of the previous neural behavior. Then individual reinforcement is a product of the reinforcement signal * the population signal * the eligibility trace (the last per synapse). Roughly, if the population signal is different than the eligability trace, and the behavior is wrong, then that synapse should be reinforced. and vice-versa.
  • PMID-17444757 Reinforcement learning through modulation of spike-timing-dependent synaptic plasticity.
    • seems to give about the same result as above, except with STDP: reinforcement-modulated STDP with an eligibility trace stored at each synapse permits learning even if a reward signal is delayed.
    • network can learn XOR problem with firing-rate or temporally coded input.
    • they want someone to look for reward-moduled STDP. paper came out June 2007.
  • PMID: Metaplasticity: the plasticity of synaptic plasticity (1996, Mark Bear)
    • there is such thing as metaplasticity! (plasticity of plasticity, or control over how effective NMDAR are..)
    • he has several other papers on this topic after this..
  • PMID-2682404 Reward or reinforcement: what's the difference? (1989)
    • reward = certain environmental stimuli have the effect of eliciting approach responses. ventral striatum / nucleus accumbens is instrumental for this.
    • reinforcement = the tendency of certain stimuli to strengthen stimulus-response tendencies. dorsolateral striatum is used here.
  • PMID-9463469 Rapid plasticity of human cortical movement representation induced by practice.
  • used TMS to evoke isolated and directionally consistent thumb movements.
  • then asked the volunteers to practice moving their thumbs in an opposite direction
  • after 5-30 minutes of practice, then TMS evoked a response in the practiced direction. wow! this may be short-term memory or the first step in skill learning.
  • PMID-12736341 Learning input correlations through nonlinear temporally asymmetric Hebbian plasticity.
    • temporally asymmetric plasticity is apparently required for a stable network (aka no epilepsy?), and can be optimized to represent the temporal structure of input correlations.

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

PMID-18429703 Psychophysical evaluation for visual prosthesis.

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

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ref: Schultz-1998.07 tags: dopamine reward reinforcement_learning review date: 12-07-2011 04:16 gmt revision:1 [0] [head]

PMID-9658025[0] Predictive reward signal of dopamine neurons.

  • hot article.
  • reasons why midbrain Da is involved in reward: lesions, receptor blocking, electrical self-stimulation, and drugs of abuse.
  • DA neurons show phasic response to both primary reward and reward-predicting stimul.
  • 'All responses to rewards and reward-predicting stimuli depend on event predictability.
  • Just think of the MFB work with the rats... and how powerful it is.
  • most deficits following dopamine-depleting lesions are not easily explained by a defective reward signal (e.g. parkinsons, huntingtons) -> implying that DA has two uses: the labeling of reward, that the tonic enabling of postsynaptic neurons.
    • I just anticipated this, which is good :)
    • It is still a mystery how the neurons in the midbrain determine to fire - the pathways between reward and behavior must be very carefully segregated, otherwise we would be able to self-simulate
      • the pure expectation part of it is bound play a part in this - if we know that a certain event will be rewarding, then the expectation will diminish DA release.
  • predictive eye movements amerliorate behavioral perfromance through advance focusing. (interesting)
  • predictions are used in industry:
    • Internal Model Control is used in industry to predict future system states before they actually occur. for example, the fly-by-wire technique in aviation makes decisions to do particular manuvers based on predictable forthcoming states of the plane. (Like a human)
  • if you learn a reaction/reflex based on a conditioned stimulus, the presentation of that stimulus sets the internal state to that motivated to achieve the primary reward. there is a transfer back in time, which, generally, is what neural systems are for.
  • animals avoid foods that fail to influence important plasma/brain parameters, for example foods lacking essential amino acids like histidine, threonine, or methionine. In the case of food, the appearance/structure would be used to predict the slower plasma effects, and hence influence motivation to eat it. (of course!)
  • midbrain groups:
    • A8 = dorsal to lateral substantia nigra
    • A9 = pars compacta of substantia nigra, SNc
    • A10 = VTA, media to substantia nigra.
  • The characteristic polyphasic, relatively long impulses discharged at low frequencies make dpamine neurons easily distinguishable from other midbrain neurons.

____References____

[0] Schultz W, Predictive reward signal of dopamine neurons.J Neurophysiol 80:1, 1-27 (1998 Jul)

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ref: BuzsAki-1996.04 tags: hippocampus neocortex theta gamma consolidation sleep Buzsaki review learning memory date: 12-07-2011 02:31 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

PMID-8670641[0] The hippocampo-neocortical dialogue.

  • the entorhinal ctx is bidirectionally conneted to nearly all areas of the neocortical mantle.
  • Buzsaki correctly predicts that information gathered during exploration is played back at a faster scale during synchronous population busts during (comnsummatory) behaviors.
  • looks like a good review of the hippocampus, but don't have time to read it now.
  • excellent explanation of the anatomy (with some omissions, click through to read the caption):
  • SPW = sharp waves, 40-120ms in duration. caused by synchronous firing in much of the cortex ; occur 0.02 - 3 times/sec in daily activity & during slow wave sleep.
    • BUzsaki thinks that this may be related to memory consolidation.
  • check the cited-by articles : http://cercor.oxfordjournals.org/cgi/content/abstract/6/2/8
____References____
[0] Buzsaiki G, The hippocampo-neocortical dialogue.Cereb Cortex 6:2, 81-92 (1996 Mar-Apr)

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ref: Graves-2001.04 tags: sleep memory REM protein synthesis review date: 03-25-2009 15:23 gmt revision:1 [0] [head]

PMID-11250009[0] Sleep and memory: a molecular perspective.

  • inhibition of protein synthesis is most effective if it occurs at a time post-training when rapid eye movement (REM) sleep is required for memory consolidation
  • The neurochemical changes that occur across sleep/wake states, especially the cholinergic changes that occur in the hippocampus during REM sleep, might provide a mechanism by which sleep modulates specific cellular signaling pathways involved in hippocampus-dependent memory storage.
    • REM sleep could influence the consolidation of hippocampus-dependent long-term memory if it occurs during windows that are sensitive to cholinergic or serotonergic signaling.
    • PKA activation seems important to hippocampal long-term memory
    • NMDA affects PKA through Ca2+ to adenyl cyclase
    • 5-HT_1A receptor negatively coupled to adenyl cyclase (AC)
    • 5-HT concentrations go down in hippocampus during sleep ?

____References____

[0] Graves L, Pack A, Abel T, Sleep and memory: a molecular perspective.Trends Neurosci 24:4, 237-43 (2001 Apr)

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ref: Eusebio-2009.05 tags: DBS STN beta gamma oscillations synchrony tremor review date: 03-23-2009 18:32 gmt revision:1 [0] [head]

PMID-19233172[0] Synchronisation in the beta frequency-band - The bad boy of parkinsonism or an innocent bystander?

  • Excessive synchronisation of basal ganglia neuronal activity in the beta frequency band has been implicated in Parkinson's disease
  • However, the extent to which beta synchrony has a mechanistic (rather than epiphenomenal) role in parkinsonism remains unclear, and the suppression of this activity by deep brain stimulation is contentious.
PMID-16289053[1] Intra-operative STN DBS attenuates the prominent beta rhythm in the STN in Parkinson's disease.
  • Beta rhythm for them = 11-30Hz. Observed in the LFP recorded from the DBS electrode itself.
  • This study shows for the first time that STN DBS attenuates the power in the prominent beta band recorded in the STN of patients with PD.

____References____

[0] 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)
[1] 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: Stickgold-2001.11 tags: review dream sleep REM NREM SWS learning memory replay date: 03-19-2009 17:09 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

PMID-11691983[0] Sleep, Learning, and Dreams: Off-line Memory Reprocessing

  • sleep can be broadly divided into REM (rapid eye movement) and NREM (no rapid eye movement) sleep, with the REM-NREM cycle lasting 90 minutes in humans.
  • REM seems involved in proper binocular wiring in the visual cortex, development of problem solving skills, and discrimination tasks.
    • REM sleep seems as important as visual experience for wiring binocular vision.
  • REM seems critical for learning procedural memories, but not declarative (by the authors claim that the tasks used in declarative tests are too simple).
    • Depriving rats of REM sleep can impair procedural learning at test points up to a week later.
    • SWS may be better for consolidation of declarative memory.
  • Strongest evidence comes from a visual texture discrimination task, where improvements are only seen after REM sleep.
    • REM has also been shown to have an effect in learning of complex logic games, foreign language acquisition, and after intensive studying.
    • Solving anagrames stronger after being woken up from REM sleep. (!)
  • REM (hypothetically) involves NC -> hippocampus; SWS involves hippocampus -> NC (hence declarative memory). (Buzaki 1996).
    • This may use theta waves, which enhance LTP in the hippocampus; the slow large depolarizations in SWS may facilitate LTP in the cortex.
  • Replay in the rat hippocampus:
    • replay occurs within layer CA1 during SWS for a half hour or so after learning, and in REM after 24 hours.
    • replay shifts from being in-phase with the theta wave activity (e.g. helping LTP) to being out of phase (coinicident with troughs, possibly used to 'erase' memories from the hippocampus?); this is in accord with memories becoming hippocampally independent.
  • ACh levels are at waking levels or higher, and levels of NE (noradrenergic) & 5-HT go near zero.
  • DLPFC (dorsolateral prefrontal cortex) is inhibited during REM sleep - presumably, this results in an inability to allocate attentional resources.
  • ACC (anterior cingulate cortex), MFC (medial frontal cortex), and the amygdala are highly active in REM sleep.
  • if you block correlates of learning - PKA pathwat, zif-268 genes during REM, learning is impaired.
  • In the context of a multilevel system of sleep-dependent memory reprocessing, dreams represent the conscious awareness of complex brain systems involved in the reprocessing of emotions and memories during sleep.
    • the whole section on dreaming is really interesting!

____References____

[0] Stickgold R, Hobson JA, Fosse R, Fosse M, Sleep, learning, and dreams: off-line memory reprocessing.Science 294:5544, 1052-7 (2001 Nov 2)

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ref: Yelnik-2008.12 tags: basal ganglia model review date: 02-17-2009 17:47 gmt revision:0 [head]

PMID-18808769 Modeling the organization of the basal ganglia.

  • wow, a concrete and descriptive model! nice!
  • can't get at the PDF / fulltext though.

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ref: Allman-2001.05 tags: anterior cingulate dopamine spindle neurons review date: 12-15-2008 04:13 gmt revision:1 [0] [head]

PMID-11411161[0] The anterior cingulate cortex. The evolution of an interface between emotion and cognition

  • The ACC receives one of the riches dopaminergic innervations of any cortical area.
  • The ACC contains morphologically distinct spindle cells, a recent advance in hominid evolution. (Appears that they are also present in monkeys, since people can perform experiments there too).
  • A large body of EEG data indicates that the anterior cingulate is the source of a 4- to 7-Hertz signal present when the subject is performing a task requiring focused concentration.24 The amplitude of this signal increases with task difficulty.25 When the subject is restless and anxious, the signal is reduced or eliminated; when the anxiety is relieved with drugs, the signal is restored.

____References____

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ref: Schultz-2000.12 tags: review reward dopamine VTA basal ganglia reinforcement learning date: 10-07-2008 22:35 gmt revision:1 [0] [head]

PMID-11257908[0] Multiple Reward Signals in the Brain

  • deals with regions in the brain in which reward-related activity has been found, and specifically what the activity looks like.
  • despite the 2000 date, the review feels somewhat dated?
  • similar to [1] except much sorter..

____References____

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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!

____References____

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ref: Buonomano-1998.01 tags: cortical plasticity learning review LTD LTP date: 10-07-2008 03:27 gmt revision:1 [0] [head]

PMID-9530495[0] Cortical plasticity: from synapses to maps

  • focuses on synaptic plasticity as the underlying mechanism of behavior-dependent cortical maps/representations.
  • "within limits, the cortex can allocate cortical area in a use-dependent manner"
  • synaptic plasticity -> STDP via NMDA, etc.
    • demonstrated with intracellular recordings of cat M1 & simultaneous stimulation of the ventrolateral thalamus & intracellular depolarization. Facilitation was short lasting and not present in all neurons.
    • demonstrated in rat auditory cortex / recording in layer 2/3 , stimulate layer 2/3 & White matter/6.
    • review of Ca+ hypothesis of LTP/LTD balance: if the Ca+ influc is below a threshold, LTD occurs; if it is above a certain threshold, LTP.
      • not sure how long LTD has been demonstrated -- 15 min?
  • cellular conditioning = direct induction of plastic changes in the selective responses of individual neurons in vivo as a result of short-term conditioning protocols. this is what we are interested in, for now.
    • this review does not explicitly deal with BG-DA / ACh reinforcement, only timing dependent plasticity, in visual and auditory cortex.
  • cortical plasticity:
    • talk about the revealing/unmasking of hidden responses when sections of cortex are deafferented or digits were amputated.
    • talk about training-based approaches: training increases cortical representation of a sensory modality / skill/ etc. The cortex can differentially 'allocate' area in a use-dependent manner throughout life.
    • cortical map changes are not reflected by changes in thalamic somatotopy.

____References____

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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.

____References____

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ref: notes-0 tags: Clementine review organize Miguel 042707 movies videos date: 04-29-2007 19:13 gmt revision:14 [13] [12] [11] [10] [9] [8] [head]

things that I want to send to miguel:

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ref: Fregni-2005.12 tags: TMS parkinsons M1 SMA review date: 04-25-2007 17:12 gmt revision:2 [1] [0] [head]

TMS for the treatment of parkinson's?

____References____

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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

____References____

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ref: Birbaumer-2007.03 tags: BMI operant conditioning review BCI date: 04-09-2007 14:25 gmt revision:0 [head]

PMID-17234696[0] Brain-computer interfaces: communication and restoration of movement in paralysis

  • A large gap between the promises of invasive animal and human BCI preparations and the clinical reality characterizes the literature: while intact monkeys learn to execute more or less complex upper limb movements with spike patterns from motor brain regions alone without concomitant peripheral motor activity usually after extensive training, clinical applications in human diseases such as amyotrophic lateral sclerosis and paralysis from stroke or spinal cord lesions show only limited success, with the exception of verbal communication in paralysed and locked-in patients.
  • attempts to train completely locked-in patients with BCI communication after entering the complete locked-in state with no remaining eye movement failed (!)
  • We propose that a lack of contingencies between goal directed thoughts and intentions may be at the heart of this problem. I'm not sure if 'contingencies' (something that can happen, but is generally not anticipated); should there not be a strong causal relationship between brain activity and prosthetic control?
  • still, the focus of this article are non-invasive BMIs.

____References____

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ref: Schwartz-2004.01 tags: Schwartz BMI prosthetics M1 review 2004 date: 04-05-2007 16:12 gmt revision:1 [0] [head]

PMID-15217341[0] Cortical Neuro Prosthetics

  • closed-loop control improves performance. see [1]
    • adaptive learning tech, when coupled to the adaptability of the cortex, suggests that these devices can function as control signals for motor prostheses.

____References____

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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.

____References____

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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