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

[0] Bevan MD, Magill PJ, Terman D, Bolam JP, Wilson CJ, Move to the rhythm: oscillations in the subthalamic nucleus-external globus pallidus network.Trends Neurosci 25:10, 525-31 (2002 Oct)[1] Bevan MD, Magill PJ, Hallworth NE, Bolam JP, Wilson CJ, Regulation of the timing and pattern of action potential generation in rat subthalamic neurons in vitro by GABA-A IPSPs.J Neurophysiol 87:3, 1348-62 (2002 Mar)[2] Magill PJ, Bolam JP, Bevan MD, Dopamine regulates the impact of the cerebral cortex on the subthalamic nucleus-globus pallidus network.Neuroscience 106:2, 313-30 (2001)[3] Magill PJ, Bolam JP, Bevan MD, Relationship of activity in the subthalamic nucleus-globus pallidus network to cortical electroencephalogram.J Neurosci 20:2, 820-33 (2000 Jan 15)

[0] Beurrier C, Bezard E, Bioulac B, Gross C, Subthalamic stimulation elicits hemiballismus in normal monkey.Neuroreport 8:7, 1625-9 (1997 May 6)

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

[0] Musallam S, Corneil BD, Greger B, Scherberger H, Andersen RA, Cognitive control signals for neural prosthetics.Science 305:5681, 258-62 (2004 Jul 9)

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ref: -2015 tags: winner take all sparsity artificial neural networks date: 03-28-2020 01:15 gmt revision:0 [head]

Winner-take-all Autoencoders

  • During training of fully connected layers, they enforce a winner-take all lifetime sparsity constraint.
    • That is: when training using mini-batches, they keep the k percent largest activation of a given hidden unit across all samples presented in the mini-batch. The remainder of the activations are set to zero. The units are not competing with each other; they are competing with themselves.
    • The rest of the network is a stack of ReLU layers (upon which the sparsity constraint is applied) followed by a linear decoding layer (which makes interpretation simple).
    • They stack them via sequential training: train one layer from the output of another & not backprop the errors.
  • Works, with lower sparsity targets, also for RBMs.
  • Extended the result to WTA covnets -- here enforce both spatial and temporal (mini-batch) sparsity.
    • Spatial sparsity involves selecting the single largest hidden unit activity within each feature map. The other activities and derivatives are set to zero.
    • At test time, this sparsity constraint is released, and instead they use a 4 x 4 max-pooling layer & use that for classification or deconvolution.
  • To apply both spatial and temporal sparsity, select the highest spatial response (e.g. one unit in a 2d plane of convolutions; all have the same weights) for each feature map. Do this for every image in a mini-batch, and then apply the temporal sparsity: each feature map gets to be active exactly once, and in that time only one hidden unit (or really, one location of the input and common weights (depending on stride)) undergoes SGD.
    • Seems like it might train very slowly. Authors didn't note how many epochs were required.
  • This, too can be stacked.
  • To train on larger image sets, they first extract 48 x 48 patches & again stack...
  • Test on MNIST, SVHN, CIFAR-10 -- works ok, and well even with few labeled examples (which is consistent with their goals)

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ref: -0 tags: VARNUM GEVI genetically encoded voltage indicators FRET Ace date: 03-18-2020 17:12 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-30420685 Fast in-vivo voltage imaging using a red fluorescent indicator

  • Kannan M, Vasan G, Huang C, Haziza S, Li JZ, Inan H, Schnitzer MJ, Pieribone VA.
  • Other genetically encoded voltage indicators (GEVI):
    • PMID-22958819 ArcLight (Peribone also last author) ; sign of ΔF/F\Delta F / F negative, but large, 35%! Slow tho? improvement in speed
    • ASAP3 ΔF/F\Delta F / F large, τ=3ms.\tau = 3 ms.
    • PMID-26586188 Ace-mNeon FRET based, Acetabularia opsin, fast kinetics + brightness of mNeonGreen.
    • Archon1 -- fast and sensitive, found (like VARNUM) using a robotic directed evolution or direct search strategy.
  • VARNAM is based on Acetabularia (Ace) + mRuby3, also FRET based, found via high-throughput voltage screen.
  • Archaerhodopsin require 1-12 W/mm^2 of illumination, vs. 50 mw/mm^2 for GFP based probes. Lots of light!
  • Systematic optimization of voltage sensor function: both the linker region (288 mutants), which affects FRET efficiency, as well as the opsin fluorophore region (768 mutants), which affects the wavelength of absorption / emission.
  • Some intracellular clumping (which will negatively affect sensitivity), but mostly localized to the membrane.
  • Sensitivity is still imperfect -- 4% in-vivo cortical neurons, though it’s fast enough to resolve 100 Hz spiking.
  • Can resolve post-synaptic EPSCs, but < 1 % ΔF/F\Delta F/F .
  • Tested all-optical ephys using VARNAM + blueshifted channelrhodopsin, CheRiff, both sparsely, and in PV targeted transgenetic model. Both work, but this is a technique paper; no real results.
  • Tested TEMPO fiber-optic recording in freely behaving mice (ish) -- induced ketamine waves, 0.5-4Hz.
  • And odor-induced activity in flies, using split-Gal4 expression tools. So many experiments.

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ref: -0 tags: 3D SHOT Alan Hillel Waller 2p photon holography date: 05-31-2019 22:19 gmt revision:4 [3] [2] [1] [0] [head]

PMID-29089483 Three-dimensional scanless holographic optogenetics with temporal focusing (3D-SHOT).

  • Pégard NC1,2, Mardinly AR1, Oldenburg IA1, Sridharan S1, Waller L2, Adesnik H3,4
  • Combines computer-generated holography and temporal focusing for single-shot (no scanning) two-photon photo-activation of opsins.
  • The beam intensity profile determines the dimensions of the custom temporal focusing pattern (CTFP), while phase, a previously unused degree of freedom, is engineered to make 3D holograph and temporal focusing compatible.
  • "To ensure good diffraction efficiency of all spectral components by the SLM, we used a lens Lc to apply a small spherical phase pattern. The focal length was adjusted so that each spectral component of the pulse spans across the short axis of the SLM in the Fourier domain".
    • That is, they spatially and temporally defocus the pulse to better fill the SLM. The short axis of the SLM in this case is Y, per supplementary figure 2.
  • The image of the diffraction grating determines the plane of temporal focusing (with lenses L1 and L2); there is a secondary geometric focus due to Lc behind the temporal plane, which serves as an aberration.
  • The diffraction grating causes the temporal pattern to scan to produce a semi-spherical stimulated area ('disc').
  • Rather than creating a custom 3D holographic shape for each neuron, the SLM is after the diffraction grating -- it imposes phase and space modulation to the CTFP, effectively convolving it with a holograph of a cloud of points & hence replicating at each point.

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

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

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

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

Why palladium?


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

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


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

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

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

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

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

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

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


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

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

A damage-tolerant glass

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

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

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

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

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

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

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

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

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

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

____References____

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

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

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

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

____References____

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

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

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

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

____References____

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

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

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

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

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ref: Rosin-2011.1 tags: PD closed loop DBS globus pallidus oscillations STN Vaadia heterodyne beta date: 03-26-2012 16:23 gmt revision:16 [15] [14] [13] [12] [11] [10] [head]

PMID-22017994[0] Closed-loop deep brain stimulation is superior in ameliorating parkinsonism.

  • Also reviewed by Rui Costa: PMID-22017983[1]
    • Good, brief review -- with appropriate minimal references.
  • Partial goal of the work: parameter determination and optimization can take a long time, and are typically only done every 3-6 months initially. But the actually changes of activity / responsiveness occur on a faster timescale in the disease, even instantaneous; other studies have shown that updating the stimulation parameters more frequently helps patients. (of course, this is a different form of closed-loop).
  • Pathology: intermittent neuronal oscillations in the basal ganglia and motor cortex commonly observed.
    • In MPTP treated primates these oscillations occur in the tremor band (theta, 4-7Hz), and double-tremor band (9-15Hz, alpha) (Bergman et al 1994 {120}, Ras et al 2000 PMID-11069964 ).
    • Actual pathology still inconclusive; talk about disruption of pathological patterns and 'focal inhibition', but this is no thorough review by any estimate.
  • "In recent years, the role of pathological discharge patterns in the parkinsonian brain has emerged as pivotal in the disease pathology
    • Eusebio and Brown, 2007;
    • Hammond et al., 2007;
    • Kuhn et al., 2009;
    • Tass et al., 2010;
    • Vitek, 2008;
    • Weinberger et al., 2009;
    • Wichmann and DeLong, 2006;
    • Zaidel et al., 2009.
    • Automatic systems should disrupt this pattern of discharge (Feng 2006, Tass 2003).
      • However, the role of these oscillations as the neuronal correlate of PD motor symptoms is still debated (Hammond et al., 2007; Leblois et al., 2007; Lozano and Eltahawy, 2004; McIntyre et al., 2004; Tass et al., 2010; Vitek, 2002; Weinberger et al., 2009 {1089}).
  • 2 african green monkeys, MPTP treatment.
  • Recorded from GPi & M1 (127 and 210 neurons); stimulated GPi, 7 pulses at 130Hz, 80ms after spike from reference area (M1 or GPi).
    • 80ms delay coincided with the next double-tremor oscillatory burst (12.5Hz)
    • State of neuronal oscillatory discharge of cortico-BG loops often accompanied by synchronization btw cortex and BG (see also quote below)
    • GPi following M1 activity superior (GP|M1 in their notation).
    • single pulses did not work.
    • Stimulation: 80uA 200us bipolar biphasic (small and short!).
  • Stimiulus protocol (M1 trigger) abolishes oscillatory activity in recorded GPi neurons.
  • Also reduced akinesia as measured with an accelerometer & decreased firing rate in the GPi.
    • Both work better than constant 130Hz DBS.
    • Also much more irregular: fewer stimulation pulses at longer latency.
  • Open loop control (the control) did much less regarding FR oscillations & bursts and reduction in firing rate.
    • Dorval et al 2010: increasing the stimulus irregularity of open-loop DBS decreases its beneficial clinical effectcs. (also Baker et. al 2011).
  • GP train stimulation triggered on GP firing significantly worsened akinesia, despite the fact that the pallidial FR decreased.
    • Treatment increased spike oscillation at double-tremor frequency in M1.
  • Oscillations more important than firing rate changes (new vs. old hypothesis).
    • pallidal oscillatory activity was not correlated to the pallidal discharge rate either before or during the application of standard DBS or GP|M1.
  • In our data, may have double-frequency tremor effects. Heterodyne should detect this.
    • "Studies on the dynamics of the entire cortico-basal ganglia loops have frequently reported the emergence of intra-and interloop component synchrony and oscillatory activity."
    • "Nevertheless, the somewhat intuitive connection between neuronal oscillations and parkinsonian motor symptoms, which include rest and action tremors, has been challenged (Hammond et al., 2007 PMID-17532060 ; Leblois et al., 2007 {1146}; Lozano and Eltahawy, 2004; Tass et al., 2010 {1147}; Vitek, 2002; Weinberger et al., 2009). For instance, while the parkinsonian rest tremor occurs mainly at the 4–7 Hz frequency band, the oscillatory neuronal activity is observed in several characteristic frequency bands in both human PD patients (Hutchison et al., 2004) {1156} and animal models (Bergman et al 1994, Gubellini et al 2009) {1074}"
      • This also has import to our heterodyne results!
    • Synchrony between globus pallidus and M1 is dynamic and state-dependent (whatever that means -- have to check the refs, Levy et al 2002 {829}, Timmerman et al 2003 {1087})
  • Quote: "... it suggests that reduction of the abnormal parkinsonian oscillatory activity could in fact be the underlying mechanism by which DBS exerts its action and brings about the associated clinical improvement."
  • Neuronal oscillatory activity occurs as high as the beta-band, 15-35Hz, hence clinical app. would need a tuned antiphase lag.
  • Suggest that the closed-loop treatment may be applicable to other diseases with characteristic firing patterns, like schizophrenia.
  • Since synchonization and oscillations hend to coincide, .. we found this too.
    • Heimer et al 2006 {1076}: oscillations and synchrony can exist independently.
  • Figure suck. Text inconsistent and frequently too small.
    • Wavelet spectrograms are nice tho.

Other thoughts:

  • Somebody should measure the transfer function of the BG / cortical loop. H(z).
  • This seems like adding a comb-filter or zero at a particular frequency: GP|GP stimluation exacerbated the effect, GP|M1 minimized the effect as there is a negation in there. (e.g. GP actviity decreases firing of M1, and vice versa).

____References____

[0] Rosin B, Slovik M, Mitelman R, Rivlin-Etzion M, Haber SN, Israel Z, Vaadia E, Bergman H, Closed-loop deep brain stimulation is superior in ameliorating parkinsonism.Neuron 72:2, 370-84 (2011 Oct 20)
[1] Santos FJ, Costa RM, Tecuapetla F, Stimulation on demand: closing the loop on deep brain stimulation.Neuron 72:2, 197-8 (2011 Oct 20)

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

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

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

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ref: Hashimoto-2003.03 tags: DBS STN subthalamic nucleus globus pallidus electrophysiology date: 03-07-2012 21:57 gmt revision:3 [2] [1] [0] [head]

PMID-12629196[0] Stimulation of the Subthalamic Nucleus Changes the Firing Pattern of Pallidal Neurons

  • why does STN stim work? investigated the effects of STN HFS on neuronal activity of GPi and GPe.
  • monkeys were treated with MPTP
  • used a scaled-down version of human DBS stimulator (cool!)
  • high frequency stimulation resulted in stimulus-synchronized regular firing pattern, plus an overall increase in pallidal firing rate.
    • they think that this synchrony may underlie the beneficial effect of HFS in the STN
  • only behavior was, apparently, what amplitude and frequency were required to alleviate parkinsonian symptoms.
  • if i do DBS in normal monkeys, is there anything to say that the effect will be similar or comparable to treatment stimulation?
  • they remind us that HFS = lesion in terms of alleviating symptoms of parkinsons.

____References____

[0] Hashimoto T, Elder CM, Okun MS, Patrick SK, Vitek JL, Stimulation of the subthalamic nucleus changes the firing pattern of pallidal neurons.J Neurosci 23:5, 1916-23 (2003 Mar 1)

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

PMID-2479133 The functional anatomy of basal ganglia disorders.

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

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

Saccades:

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

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ref: Iansek-1980.04 tags: globus pallidus GPe GPi electrophysiology 1980 date: 02-29-2012 18:17 gmt revision:2 [1] [0] [head]

PMID-7411442 The monkey globus pallidus: neuronal discharge properties in relation to movement.

  • motor units are generally inactive during inactivity. the relationship to movement of the discharges of such neurons was found to be very specific
    • This is in comparison to other results, which report a sustained firing, esp in GPi.
  • the discharges (as analyzed through histograms) of many neurones were related to only a particular direction of movement about one joint in the right limb.
  • some discharges were related to multijoint movements -> probably due to control of contraction of particular muscles.
    • nonetheless, this relationship was a loose one; there is not a tight coupling between pallidal activity and muscle contraction.
  • some responded to ipsilateral as well as contralateral movements.
    • PMID-7925805 Unilateral leasions in the GP results in bilateral increase in reaction time. hence, GP is involved in initiation. RT speed eventually recovered.
  • only the posterior globus pallidus - well posterior to the maximum expansion - contained movement related cells.
    • the a-p stereotaxic coordinates were less useful than the location of the maximum mediolateral width of the structure.
    • cells occurred in clusters, separated by regoins of non-movement related.
  • cells in the internal segment had no such organization.
  • many of the non-movement related neurons were tonically active.
  • this was before there was A/D recording, apparently!

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ref: -0 tags: distrupted oscillations Mallet 2008 6-OHDA globus pallidus date: 02-29-2012 01:15 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-19109506 Parkinsonian beta oscillations in the external globus pallidus and their relationship with subthalamic nucleus activity.

  • Rat 6-OHDA.
  • On rate model: Although synchronization of GP unit activity increased by almost 100-fold during beta oscillations, the mean firing rate of GP neurons decreased compared with controls.
  • Synchronized firing persisted across different brain states, suggesting hardwiring.
  • GP and STN are frequency aligned but phase skewed.
    • Lateral inhibition in GP seems essential / see model.
  • Suggest that GPe / STN could generate oscillations that propagate to the rest of the BG.
    • But then why is the cortex required?

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ref: -0 tags: oscillations DBS globus pallidus parkinsons date: 02-28-2012 17:24 gmt revision:1 [0] [head]

PMID-17880401 Late emergence of synchronized oscillatory activity in the pallidum during progressive Parkinsonism.

  • In monkeys, progressive dopamine depetion process, recording changes during disease progression -- good!
  • No big change in firing rates, makes sense as this is likely controlled by other network or cellular homeostatic mechanisms.
  • Early in intoxication inhibitory responses to movement disappeared.
    • Yet synchrony did not appear at this time -- it is a sequelae?
    • Correlated activity appeared later, once the animals became severly akinetic.
  • Thus, a causality between the emergence of synchronous oscillations in the pallidum and main parkinsonian motor symptoms seems unlikely.
  • Probably it's movement related activity, not overall states. YES.

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

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

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

____References____

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

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

PMID-4997823 Activity of Pallidal Neurons During Movement

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

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ref: Carpenter-1981.11 tags: STN subthalamic nucleus anatomy tracing globus_pallidus PPN substantia_nigra DBS date: 02-22-2012 22:01 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

PMID-7284825[0] Connections of the subthalamic nucleus in the monkey.

  • STN projects to both segments of the globus pallidus in a laminar and organized fashion.
    • most fibers projected to the lateral pallidal segment (aka GPe).
  • also projected to specific thalamic nuclei (VAmc, VLm, DMpl).
  • the major projection of PPN is to SN.
  • striatum projects to the substantia nigra pars reticulata (SNr). interesting.
  • see also: PMID-1707079[1]
    • "Anterograde transport in fibers and terminal fields surrounded retrogradely labeled cells in the LPS (GPe), suggesting a reciprocal relationship [to the STN]"
  • These data suggest that the STN receives its major subcortical input from cell of the LPS (GPe) arranged in arrays which have a rostrocaudal organization.
  • No cells of the MPS (GPi) or SN project to the STN.
  • The output of the STN is to both segments of the GP and SNpr.
  • Major subcortical projections to PPN arise from the MPS (GPi) and SNpr (output of the BG) , but afferents also arise from other sources.
    • The major projection of PPN is to SN.
    • HRP injected into PPN produced profuse retrograde transport in cells of the MPS and SNpr and distinct label in a few cells of the zona incerta and STN.

____References____

[0] Carpenter MB, Carleton SC, Keller JT, Conte P, Connections of the subthalamic nucleus in the monkey.Brain Res 224:1, 1-29 (1981 Nov 9)
[1] Carpenter MB, Jayaraman A, Subthalamic nucleus of the monkey: connections and immunocytochemical features of afferents.J Hirnforsch 31:5, 653-68 (1990)

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ref: Boulet-2006.1 tags: hemiballismus PD parkinsons STN subtalamic DBS dyskinesia rats 2006 glutamate date: 02-22-2012 18:58 gmt revision:1 [0] [head]

PMID-17050715 Subthalamic Stimulation-Induced Forelimb Dyskinesias Are Linked to an Increase in Glutamate Levels in the Substantia Nigra Pars Reticulata

  • STN-HFS-induced forelimb dyskinesia was blocked by microinjection of the Glu receptor antagonist kynurenate into the SNr and facilitated by microinjection of a mixture of the Glu receptor agonists AMPA and NMDA into the SNr.
    • Well, that just makes sense. STN is excitatory, GPi is an output structure of the BG, and stimulation should activate the area.

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

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

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

____References____

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

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

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

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

____References____

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

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

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

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

____References____

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ref: Magill-2001.01 tags: dopamine STN globus_pallidus cortex parkinsons DBS 6OHDA date: 02-22-2012 15:31 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

PMID-11566503[0] Dopamine regulates the impact of the cerebral cortex on the subthalamic nucleus-globus pallidus network

  • Compared unit activity STN / GP and EEG in rats under urethane anesthesia in control and 6OHDA rats.
  • DA depletion:
    • increased FR of STN neurons.
    • caused oscillations in GP neurons.
  • dopamine depletion causes the STN-GP circuit to become more reactive to the influence of the activity of cortical inputs. also see PMID-10632612[1]
  • oscillatory activity in the STN-GP network in anaesthetised rats is phase-locked to rhythmic cortical activity and is abolished by transient cortical activation as well as cortical ablation.
    • 15-20% of the network still oscillated following cortex removal, suggesting that intrinsic properties pattern activity when dopamine levels are reduced.
  • cool figures - nice recordings, high SNR, clear oscillations in the firing and ECoG signal

____References____

[0] Magill PJ, Bolam JP, Bevan MD, Dopamine regulates the impact of the cerebral cortex on the subthalamic nucleus-globus pallidus network.Neuroscience 106:2, 313-30 (2001)
[1] Magill PJ, Bolam JP, Bevan MD, Relationship of activity in the subthalamic nucleus-globus pallidus network to cortical electroencephalogram.J Neurosci 20:2, 820-33 (2000 Jan 15)

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ref: Guridi-2001.01 tags: STN DBS 2001 parkinsons hemiballismus Obeso date: 02-22-2012 15:14 gmt revision:8 [7] [6] [5] [4] [3] [2] [head]

PMID-11133783[0] The subthalamic nucleus, hemiballismus and Parkinson's disease: reappraisal of a neurosurgical dogma

  • Lesions of the globus pallidus, thalamus, as well as the STN can lead to hemiballismus
  • none-the-less, hemiballismus is a rather rare complication in STN DBS or lesion
  • GABA projection to the GPi is reduced in PD due to dopamine depletion
    • STN has projects glutamergic projections to GPi, so lesion would tend to worsten activity
    • STN also projects to the GPe, and lesioning it reduces hyper-activity there.
    • Therefore the balance of lesioning is to permit movements but not hemiballismus.
  • STN lesion in normal patients induces hemibalismus and chorea, but threshold for movements are raised with chronic dopamine depletion. cf {207}
  • Quality of life issues: perhaps everything has been learned already. {1124}

____References____

[0] Guridi J, Obeso JA, The subthalamic nucleus, hemiballismus and Parkinson's disease: reappraisal of a neurosurgical dogma.Brain 124:Pt 1, 5-19 (2001 Jan)

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ref: Bevan-2002.1 tags: STN GPe globus pallidus oscillations parkinsons DBS date: 02-22-2012 15:13 gmt revision:8 [7] [6] [5] [4] [3] [2] [head]

PMID-12220881[] Move to the rhythm: oscillations in the subthalamic nucleus-external globus pallidus network.

  • !!! autonomous oscillation of STN and GPe underlies tonic activity and is important for synaptic activity (e.g. normal??)
    • this is a review, of course.
  • during quiet wakefulness, neurons in STN and GPe fire differently without rhythm or strong correlation.
    • this is more pronounced when STN/GPe neurons are isolated from synaptic input (e.g. when prepared in a slice)-- they have inherent oscillatory characteristics. hum.
      • this may allow persistent activity or timed (gating) of planned activity (as opposed to timing of compensatory movement, which are mostly handled by the cerebellum).
      • the persistent activity must be more complicated than synchronized firing as in PD.
      • Random thought: I wonder if you 'clocked' the brain you would get discrete reaction times. Longshot; would need to review up and down states in the cortex?
  • during voluntary movement, GPe and STN neurons display a complex relationship to features of motor activity.
  • GPe and STN are reciprocally connected (STN with the Glu, GPe with the GABA)
    • as in other original papers, most of the axons from these regions have branched axons that mediate both reciprocal connections and innervation of output nuclei.
  • interesting thought: STN/GPe network could act as a 'generic' recursive pattern generator.
  • see figure 1 - single IPSP regulate the timing of spikes in the STN. large IPSP can synchronize and entrain the intrinsic high firing rate of STN neurons by prolonging the interspike interval.
    • bursts of IPSP can lead to rebound excitation, and hence a paradoxical increase in activity inn the STN. PMID-11877509[]
      • large IPSPs reset STN neurons oscillatory cycle & lead to synchronization
      • small IPSPs lead to phase-dependent delays and probably lead to desynchronization.
      • neuromodulators, like ACh, serotonin, and dopamine, can influence the polarization of STN neurons, and hence will have a profound effect on activity.
      • STN activity is more dependent one the pattern of afferent activity (of course!) than the gross magnitude of incoming spikes.
  • figure 2 - the network configuration between STN and GPe can markedly affect resulting activity. When there are possible reciprocal connections, the network produces tremor; when the network is more organized so that STN cannot recurrently activate GPe, multiple rhythms occur.
    • recall that both structures have extensive & sparsely connected dendritic fields, and are highly topographically organized.
  • figure 3 - [2,3]- oscillatory activity in the STN is a consequence of dopamine depletion and is also a feature of normal activity.
    • this is dependent on the presence of cortex. lack of cortex = regular firing.
    • GPe firing is tonic and constant in normal animals, and becomes oscillatory in 6-OHDA treated animals.
  • administration of dopamine agonists in PD patients causes higher frequency rhythms (30-70hz); without treatment, oscillations are in the 8-12 and lower range.

my notes:

  • IPSPs seem to have a very interesting and complex effect on the firing properties of tonically-active STN nenurons. who knows how this is being used, and in what representation the associated information is being processed?
  • still need to understand what dopamine is doing, and why absence leads to oscillations!
    • dopamine must modulate basal ganglia insensitivity to cortex.

____References____

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

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

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

____References____

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

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ref: Georgopoulos-1983.08 tags: STN monkeys primate Georgopoulos globus pallidus date: 02-10-2012 18:57 gmt revision:2 [1] [0] [head]

PMID-6875658[0] Relations between parameters of step-tracking movements and single cell discharge in the globus pallidus and subthalamic nucleus of the behaving monkey.

  • Step tracking task in monkeys; wrist flexion and extension.
    • first one in monkeys, apparently.
    • 87 neurons in GP, 36 in GPi, 29 in STN.
  • Linear tuning to direction and distance, same as in motor cortex by Georgopoulos.
    • More likely to see frequency increase.
  • Earlier firing rate change in STN than GPe than GPi.
  • Two patterns of firing in the globus pallidus external:
    • more frequent: high discharge rate interrupted with pauses of varying duration
    • less frequent: low average discharge rate with very high frequency bursts.
  • GPi: high frequency with frequent bursts.
  • GPi/e generally high firing rate - 80-100 Hz, with frequent bursts.
    • But not as deep movement tuning as M1.
  • Only primates have projections from the motor cortex to the STN.
    • This seems like an evolutionarily recent development -- apparently the cortex needs the extra level of control?

See also citing articles: http://scholar.google.com/scholar?cites=16339220378239936453&as_sdt=5,34&sciodt=0,34&hl=en

____References____

[0] Georgopoulos AP, DeLong MR, Crutcher MD, Relations between parameters of step-tracking movements and single cell discharge in the globus pallidus and subthalamic nucleus of the behaving monkey.J Neurosci 3:8, 1586-98 (1983 Aug)

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

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

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

____References____

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

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

PMID-16032642[0] Common causes of hemiballism.

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

____References____

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

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ref: Beurrier-1997.05 tags: STN stimulation hemiballismus 2007 DBS date: 01-26-2012 17:20 gmt revision:4 [3] [2] [1] [0] [head]

PMID-9189903[] Subthalamic stimulation elicits hemiballismus in normal monkey.

  • the effects of stimulation on normal waking primates has never been evaluated (doh!)
  • In the normal monkey, HFS appears reversibly to incapacitate the STN and allow the emergence of involuntary proximal displacements, due to disinhibition of the thalamo-cortical pathway
  • in MPTP-treated monkey HFS buffers STN activity and alleviates akinesia and rigitity by reducing inputs to the internal segment of the globus pallidus. (STN output is excitatory) (or so the theory at the time goes)
  • perhaps i will need to buy this article ;(

____References____

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

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

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

____References____

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

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

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

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

____References____

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

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

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

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

____References____

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

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

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

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

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

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

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

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

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

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ref: BarGad-2003.12 tags: information dimensionality reduction reinforcement learning basal_ganglia RDDR SNR globus pallidus date: 01-16-2012 19:18 gmt revision:3 [2] [1] [0] [head]

PMID-15013228[] Information processing, dimensionality reduction, and reinforcement learning in the basal ganglia (2003)

  • long paper! looks like they used latex.
  • they focus on a 'new model' for the basal ganglia: reinforcement driven dimensionality reduction (RDDR)
  • in order to make sense of the system - according to them - any model must ingore huge ammounts of information about the studied areas.
  • ventral striatum = nucelus accumbens!
  • striatum is broken into two, rough, parts: ventral and dorsal
    • dorsal striatum: the caudate and putamen are a part of the
    • ventral striatum: the nucelus accumbens, medial and ventral portions of the caudate and putamen, and striatal cells of the olifactory tubercle (!) and anterior perforated substance.
  • ~90 of neurons in the striatum are medium spiny neurons
    • dendrites fill 0.5mm^3
    • cells have up and down states.
      • the states are controlled by intrinsic connections
      • project to GPe GPi & SNr (primarily), using GABA.
  • 1-2% of neurons in the striatum are tonically active neurons (TANs)
    • use acetylcholine (among others)
    • fewer spines
    • more sensitive to input
    • TANs encode information relevant to reinforcement or incentive behavior

____References____

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ref: 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: Musallam-2004.07 tags: cognitive BMI Musallam Andersen PRR MIP date: 01-08-2012 23:13 gmt revision:5 [4] [3] [2] [1] [0] [head]

PMID-15247483[0] Cognitive control signals for Neural Prosthetics

  • decode intended target from 200 to 1100ms of memory period (reward on correct, etc).
  • got good success rates with relatively few neurons (like 8 for 8 targets) -- yet decode rates were not that good, not at all as good as Fetz or Schmidt.
  • used pareital reach region (PRR), a subsection of posterior partietal cortex PPC, which represents the goals of the reach in visual coordinates. In the experiment, the implanted in media intrapareital (MIP)
    • in encodes the intended goal rather than the trajectory to achieve that goal.
    • PMd also seems to encode planning activity, though less is known about that.
  • used an adaptive database to map neuronal activity to targets; eventually, the database contained only (correct) brain-control trials.
  • neuronal responses were recorded from parietal reach region (PRR) with 64 microwire electrodes in 4 monkeys, plus 32 microwire electrodes in PMd
  • monkeys were tained to fixate on the center of the screen dring the task, though free fixation was also tested and seemed to work ok.
  • monkeys had to press cue, fixate, observe target location, wait ~2 sec, and move to the (remembered) target location when cue disappeared.
  • they use a static or continually updated 'database' for predicting which of four targets the monkey wants to go to during the instructed delay task.
  • able to predict with moderate accuracy the expected value of the target as well as its (discrete) position.
  • predictions were made during the delay period while there was no motor movement.
  • predictions worked equally well for updated and static databases.
  • monkeys were able to increase their performance on the BMI trials over the course of training.
  • reward type or size modulated the tuning of BMI neurons in the ecpected way, though aversive stimuli did not increase the tuning - suggesting that the tuning is not a function of attention (maybe).
  • the database consisted of 900ms of spike recordings starting 200ms after cue for 30 reach trials for each target. spike trains were projected onto Haar wavelets (sorta like a binary tree), and the filter coefficients were used to describe P(r), the probability of response, and P(r|s), probability of response given the target. then they used bayes rule (P(r) and P(r|s) were approximated with histograms, i think) to find P(s|r) - a discrete function - which it is easy to find the maximum of.
  • adding more trials offline improved the decode performance.
  • supporting online material.

PMID-15491902 Cognitive neural prosthetics

  • LFPs are easier to record and may last longer (but they are not as 'sexy').
  • suggest future electrodes will move automatically, peizo-drive perhaps.
  • PRR receives direct visual projections & codes for reaches in visual coordinates relative to the current direction of gaze.
  • PRR can hold the plan for a movement in short-term memory.
  • 16 neurons peak..?
  • In area LIP of PPC Platt and Glimcher PMID-10421364 found cells that code the expected value of rewards.
    • 20Hz beta-band oscillation indicated the behavioral state of the animal. While planning for a saccade it slowly increased, whereas at the time of movement in dramatically increased in amplitude.
    • LFP was better than spikes for a state decode.

____References____

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ref: bookmark-0 tags: machine_learning research_blog parallel_computing bayes active_learning information_theory reinforcement_learning date: 12-31-2011 19:30 gmt revision:3 [2] [1] [0] [head]

hunch.net interesting posts:

  • debugging your brain - how to discover what you don't understand. a very intelligent viewpoint, worth rereading + the comments. look at the data, stupid
    • quote: how to represent the problem is perhaps even more important in research since human brains are not as adept as computers at shifting and using representations. Significant initial thought on how to represent a research problem is helpful. And when it’s not going well, changing representations can make a problem radically simpler.
  • automated labeling - great way to use a human 'oracle' to bootstrap us into good performance, esp. if the predictor can output a certainty value and hence ask the oracle all the 'tricky questions'.
  • The design of an optimal research environment
    • Quote: Machine learning is a victim of it’s common success. It’s hard to develop a learning algorithm which is substantially better than others. This means that anyone wanting to implement spam filtering can do so. Patents are useless here—you can’t patent an entire field (and even if you could it wouldn’t work).
  • More recently: http://hunch.net/?p=2016
    • Problem is that online course only imperfectly emulate the social environment of a college, which IMHO are useflu for cultivating diligence.
  • The unrealized potential of the research lab Quote: Muthu Muthukrishnan says “it’s the incentives”. In particular, people who invent something within a research lab have little personal incentive in seeing it’s potential realized so they fail to pursue it as vigorously as they might in a startup setting.
    • The motivation (money!) is just not there.

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ref: notes-0 tags: challenge grants NIH obama date: 12-28-2011 21:06 gmt revision:2 [1] [0] [head]

I was looking over the NIH's omnibus document (181 pages!) for the Challenge Grants due April 27, and happened upon a few interesting & relevant ones - and made some observations along the way.

  • The section on behavior modification is especially interesting -- the NIH wants to test techniques, biofeedback, treatments, cognitive therapy, behavioral therapy to, basically, improve the quality of life of the patients/citizens. Mainly this is targeted at illegal drugs. This is all very well so long as we are given a choice in the matter (it would seem so, of course -- drugs are a big problem in the US, and most of them are rightfully illegal). It is easy to change something designed to help into a tool that will help manipulate.
  • Example: 01-GM-101 Individual model of social behavior Development of a robust and well-characterized individual-based model of social behavior that includes the dynamics of social interactions that matches observed patterns of behavior. Contact: Dr. Irene Eckstrand
    • Sounds slightly big-brother like, no?
  • 01-OD(OBSSR)-101 Tools for studying cultural phenomena Development of new tools for: the measurement of culturally-shared mental phenomena (e.g. representations, scripts, prejudices); studying mechanisms by which these phenomena are transferred and adapted across individuals; and advancing research on the distribution and transmission of cultural phenomena within populations. (they list 5 scientists to contact).
    • Epidemiology meets sociology? The language they use suggests treating culture as a disease.
  • On the plus side, they also have sections for funding studies of informed consent, data access policies, responsible dissemination of research results, and the ethical considerations of all this (section 02-*)
  • A specific challenge topic states some of the guiding theory well: 04-DA-112 Enhancing the Impact of Behavioral Interventions using New and Innovative Technology. The ultimate goal of the NIH is to improve public health as measured in terms of biological well-being, which is multidimensional and strongly shaped by behavioral variables. Neuroscience on brain plasticity has demonstrated, unequivocally, that the brain changes as a result of behavior changes. Technological advances have made it possible to better measure the impact of behavioral interventions on specific biological targets and processes. [...] Dr. Lisa Onken
  • 06-OD-111 Mathematical and/or computational models of health-relevant behaviors. ...monitor social processes that occur over time. Dr. Lisa Onken. (eh, this document is not very well organized! why didn't they provide database access to it? They provide only 15 categories + two letter codes; I think that 'tagging' challenge tpoics with keywords would have been more effective, as the topics belong to overlapping fields. Of course, it is nice to see all of them; it forces you to get the big picture, something that would be missed with the focused results of a database search. )
  • 05-MD-101 Social Determinants of Health There is a growing research that reveals the important role of social determinants of health in addressing and understanding health disparities. Social determinants of health are the economic and social conditions under which people live which determine their health. We propose research that investigates interventions that address these social determinants (e.g. employment training, school readiness programs, food stamp programs, adequate and affordable housing programs). Contact Dr. Kyu Rhee
    • (next proposal): Approximately 70-80% of all current health care costs are connected with the treatment of chronic diseases.
  • 05-NS-102 Technologies to Enable Comparative Effectiveness Research in Clinical Neuroscience. Talks about looking for ways of decreasing the cost of randomized control trials.
  • 10-CA-101 Cyber-infrastructure for health: building technologies to support coordination and computational thinking The NSF as identified research based on 'cyberinfrastructure' as the single most important challenge confronting the nations science laboratories flash animation and article
  • 15-MH-110 Understanding the mechanism of action of deep brain stimulation. Conduct basic research on the mechanism of action of deep brain stimulation. Studies should be relevant to it's use in the treatment of mental disorders.
  • 06-CA-104 Quantum biology in cancer biology -- wow! I hadn't heard of the field of quantum biology.
  • 06-AG-101 Neuroscience blueprint: Development of non-invasive imaging approaches or technologies that directly assess neural activity (page 75) focus is on non-invasive methodologies, but it's possibly applicable specific challenge topic that I've seen so far.
  • 06-DA-102 Tool development for the Neurosciences (page 82) Tools that unambiguously identify, manipulate, and report from neurons in vivo and in vitro are needed to help us understand the interactions within neural circuits, to examine the functions of types of neurons that are derived from different brain regions, and to determine how selective and conditional silencing of activation of individual neurons or groups of similar neurons may alter functional outcomes, esp. behavior. (...) identification of real-time responses to drugs of abuse or therapeutic interventions ... understand endogenous neuroprotective mechanisms [and] neural dysfunction.
  • Neurolex -- mentioned. interesting.
  • 06-HD-101* Improved interfaces for prostheses to improve rehabilitation outcomes (page 91) Mechanical design and control algorithms for prosthetic limbs have seen remarkable advances recently. Still lacking, however, are robust interfaces for these limbs to both the brain and the skeleton. The foci of this challenge will be to improve functional rehabilitation outcomes by 1) developing or refining control interfaces that can utilize signals from [the] cerebral cortex to drive the latest generation of arm prostheses; 2] developing or refining methods for anchoring prosthetic arms directly to bone without risk of infection and 3) ... Contact: Dr. Michael Weinreich
  • 06-MH-102 Technologies to study neuronal signaling, plasticity, and neurodevelopment (page 96) molecular target.
  • 06-MH-103 New Technologies for neuroscience research (page 97) Develop technologies for neuroscience research that are software, hardware, or biology based. Dr. Huerta.
  • 06-NS-103 Breakthrough technologies for neuroscience (page 97) Advances in basic neuroscience are often catalyzed by the development of breakthrough technologies that allow interrogation of nervous system function (e.g. patch clamp recording from single cells, optical imaging, multi-channel recording arrays, fluorescent dyes to image cell types and intracellular processes etc) The challenge is to develop new technologies with the potential to enable basic neuroscientists to make quantum leaps in understanding nervous system development and function. Dr. Edmund Talley.
  • 06-NS-104 Developing and validating assistive neuro-technologies. mention neural control of prostheses.
  • 13-NS-101 Developing novel biomaterials to interfaces with neural activity (yes, the typo is from the original document; page 147). talk about neural-computer interfaces, repair of injured nerve or spinal cord, neurotransmission across a damage (another typo!) nerve or cord. Contact Dr. Joe Pancrazio.

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

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

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

____References____

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

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

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

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

____References____

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

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

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

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

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

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

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


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ref: -0 tags: nvidia linux driver vmalloc multiple cards grub date: 02-09-2011 13:49 gmt revision:2 [1] [0] [head]

http://www.nvnews.net/vbulletin/showthread.php?t=141845 -- when running multiple nvidia cards on one linux computer with a 32-bit kernel, you may run out of kernel memory while loading the video drivers. To fix this, pass vmaloc=256M to the kernel prior boot - e.g. by editing /boot/grub/menu.lst (grub 1) or /boot/grub/grub.cfg (grub 2)

If you want to make the change permanent with all kernels, edit

/etc/grub.d/10_linux

and add vmalloc=256M to the end of

linux   ${rel_dirname}/${basename} root=${linux_root_device_thisversion} ro ${args}

see also the Nvidia driver release notes

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ref: Kimura-1996.12 tags: putamen globus pallidus learning basal ganglia electrophysiology projection date: 10-03-2008 17:05 gmt revision:1 [0] [head]

PMID-8985875 Neural information transferred from the putamen to the globus pallidus during learned movement in the monkey.

  • study of the physiology of the projection from the striatum to the external and internal segments of the globus pallidus.
  • Identified neurons which project from the striatum to pallidus via antridromic activation after stim to the GPe / GPi.
  • there were two classes of striatal neurons:
    • tonically active neurons (TANs, rate: 4-8hz)
      • TANs were never activated by antidromic stimulation. therefore, they probably do not project to the pallidus.
    • phasically active neurons (very low basal rate, high frequency discharge in relation to behavioral tasks
      • All PANs found projected to the globus pallidus.
      • PANs were responsive to movement or movement preparation. (or not responsive to the particular behaviors investigated)
        • the PANns that showed activity before movement initiation more frequently projected to GPi and not GPE (or both - need to look at the anatomy more).
      • PANs also show bursts of activity time-locked to the initiation of movement (e.g. time locked to a particular part of the movement).
      • no neurons with sensory response!
  • when they microstimulated in the putamen, a few pallidal neurons showed exitatory response; most showed inhibitory/supressive response.

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

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

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ref: -0 tags: Debian Godi install dependencies date: 07-02-2008 20:27 gmt revision:1 [0] [head]

Notes from installing Ocaml via GODI on a Debian Lenny system (oh, dependencies!):

  1. be sure to install libpcre3-dev before starting the bootstrap2 or godi_console
  2. need libatlas-sse2-dev (on Intel) plus liblapack-dev for lacaml.
  3. need libglut3-dev to install opengl packages ; NVIDIA does not provide GLUT or even glu.h.
  4. need libxmu-dev to install lablgl
  5. need libgtk2.0-dev and libgtkgl2.0-dev to install lablgtk2.

Final list:

apt-get install libpcre3-dev libatlas-sse2-dev liblapack-dev libglut3-dev libxmu-dev libgtk2.0-dev libgtkgl2.0-dev

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ref: movie-0 tags: really great claymation date: 12-30-2007 21:54 gmt revision:2 [1] [0] [head]

Jeff Newitt: Loves me - loves me not

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ref: notes-0 tags: iceweasel firefox acroread uninstall debian linux mozplugger date: 11-10-2007 04:39 gmt revision:1 [0] [head]

Adobe acrobat reader 7.0 leaks a prodigious amount of memory on my linux system (Debian Etch, stable). However, some pdfs will only open in acroread, so i want to keep the application around for occasional use. Because of the memory leaks, it is not good to have it loaded by default by iceweasel / firefox (evince or xpdf is better). To do this:

  1. quit your browser (not sure if this is necessary, but perhaps it is a good idea).
  2. open /etc/mozpluggerrc and comment out (#) all the sections that reference acroread. There are 3 macro lines, as well as one line in in the pdf / x-pdf content handling list.
  3. goto ~/.mozilla and remove pluginreg.dat ; do the same for ~/.mozilla/firefox
  4. go to /usr/lib/iceweasel/plugins and move / remove / rename nppdf.so (if it is there) (this is what tripped me up for a while - i had to look at the automatically-generated pluginreg.dat to figure out that acroread was being loaded without mozplugger via this plugin).

that's it! :)

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ref: notes-0 tags: blackfin interrupts install date: 09-20-2007 16:49 gmt revision:2 [1] [0] [head]

things required to enable interrupts on a blackfin processor, not necessarily in order though all are required (also see the list, in the programming ref, on page 4-31):

  1. set the ISR address in the EVTx (event vector) registers. (page 4-42 in the processor programming reference)
  2. set the system interrupt controller interrupt mask (SIC_IMASK) for the events you want to accept. for the blackfin BF537, see 4-20 in the hardware reference.
  3. set the interrupt priority with the IARx registers. This is also hardware-dependent, see page 4-18 in the BF537 hardware ref. BF537 has 4 of these registers, each 32 bits.
    1. remember to put the priority minus 7 in the individual nibbles of the IAR registers - hence '3' maps to IVG10
  4. set IMASK bits appropriately -- this is not the same as the SIC_IMASK register. See page 4-39 in the programming reference.
  5. if you want to allow nested interrupts, save reti, asat, and the fp (in addition to any registers clobbered) into the stack. If not, issue a cli and an sti before concluding the in the interrupt servicing routine.
  6. close your interrupt routines with a rti instruction.

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ref: Grabli-2004.09 tags: basal_ganglia gobus_pallidus pathology GPe date: 03-11-2007 04:22 gmt revision:0 [head]

PMID-15292053 Behavioural disorders induced by external globus pallidus dysfunction in primates: I. Behavioural study.

  • there is a functional map within the basal ganglia according to its cortical projections.
  • reversible and focal dysfunction induced by microinjections if bicuculline in the sensorimotor territory of the external globus pallidus can generate abnormal movements. They wanted to test this in the other parts.
  • We found that bicuculline microinjections induced stereotypy when performed in the limbic part of the GPe, and attention deficit and/or hyperactivity when performed in the associative part
  • the behavioural effects shared similar features with symptoms observed in Tourette's syndrome, attention deficit/hyperactivity and compulsive disorders

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

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

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

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ref: Gdowski-2001.02 tags: globus pallidus reward electrophysiology 2001 date: 0-0-2007 0:0 revision:0 [head]

PMID-11160530 Context Dependency in the Globus Pallidus Internal Segment During Targeted Arm Movements

  • most of the movement-responsive neurons had modulations in the cued segment of the task, not in the subsequent relaxed, self-paced phase.
  • this constitutes a reward or context-dependence.
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ref: Cooper-2000.09 tags: globus pallidus electrophysiology current clamp channel date: 0-0-2007 0:0 revision:0 [head]

PMID-10970430 Electrophysiological and morphological characteristics of three subtypes of rat globus pallidus neurone in vitro

  • there are 3 morphological types of neurons.
    • A: inward rectfier + low-threshold calcium current = anode break depolarizations.
    • B: no inward rectifier, just fast monophasic AHP. small.
    • C: big! (...)

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ref: Wannier-2002.01 tags: globus_pallidus electrophysiology caudate putamen basal_ganglia date: 0-0-2007 0:0 revision:0 [head]

PMID-11924876 Neuronal activity in primate striatum and pallidum related to bimanual motor actions

  • monkeys had to pull on a spring-loaded drawer and grab food with other hand.
  • half the recorded neurons were responsive to this task.
  • targeted: 20.1 to 14.v mm anterior to the interaural plane of the rhesus monkey brain.
    • 19.2 mm looks good for GPe
    • 17.4 for putamen and caudate (right below area 24 in the cortex - Ventral cingulate cortex)
    • 15.6 for putamen, GPe, and GPi.
  • can these be modulated by imagined movement? e.g. in a BMI?

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ref: Di-1994.06 tags: dopamine NMDA striatum globus_pallidus ion_channels neurotransmitters date: 0-0-2007 0:0 revision:0 [head]

PMID-7521083 Modulatory functions of neurotransmitters in the striatum: ACh/dopamine/NMDA interactions.

  • in striatum, 2 basic classes of neural transmission:
    • fast neural transmission:
      • glutamate response in striatum to cortical/thalamic input via AMPA on medium spiny neurons
      • GABA output of the striatum
    • modulatory neural transmission:
      • NMDA
      • DA dopamine
      • substance P
      • ACh acetylecholine (large aspiny neurons, 30um soma! 1-2% of the population)
  • input to the cholinergic large aspiny neurons
    • GABA/substance P medium-spiny neurons which project to SNr + GPi
    • DA neurons from tegmentum, a8 a9 a10 groups
    • Glu neurons in the thalamus, and, to a lesser extent, from the cortex
  • DA D2 autoreceptors inhibit/regulate the release of DA, and it can also modulate the release of ACh + glu
    • specifically D2 has been demonstrated to inhibit ACh release, but not D1 (accourse)
  • figure 2 is kinda nice for the neurotransmitters in the basal ganglia
  • not really all that clear of an article

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ref: bookmark-0 tags: google parallel_computing GFS algorithm mapping reducing date: 0-0-2006 0:0 revision:0 [head]

http://labs.google.com/papers/mapreduce.html

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

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

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

http://www.newscientist.com/article/dn8859-methanolpowered-artificial-muscles-start-to-flex.html