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

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

[0] Atallah HE, Lopez-Paniagua D, Rudy JW, O'Reilly RC, Separate neural substrates for skill learning and performance in the ventral and dorsal striatum.Nat Neurosci 10:1, 126-31 (2007 Jan)

[0] Diedrichsen J, Hashambhoy Y, Rane T, Shadmehr R, Neural correlates of reach errors.J Neurosci 25:43, 9919-31 (2005 Oct 26)

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

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

[0] Nakahara H, Doya K, Hikosaka O, Parallel cortico-basal ganglia mechanisms for acquisition and execution of visuomotor sequences - a computational approach.J Cogn Neurosci 13:5, 626-47 (2001 Jul 1)

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

[0] Graybiel AM, Aosaki T, Flaherty AW, Kimura M, The basal ganglia and adaptive motor control.Science 265:5180, 1826-31 (1994 Sep 23)

[0] Dayan P, Balleine BW, Reward, motivation, and reinforcement learning.Neuron 36:2, 285-98 (2002 Oct 10)

[0] Graybiel AM, The basal ganglia: learning new tricks and loving it.Curr Opin Neurobiol 15:6, 638-44 (2005 Dec)

[0] Rektor I, Kaiiovský P, Bares M, Brázdil M, Streitová H, Klajblová H, Kuba R, Daniel P, A SEEG study of ERP in motor and premotor cortices and in the basal ganglia.Clin Neurophysiol 114:3, 463-71 (2003 Mar)

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

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ref: -2012 tags: cortex striatum learning carmena costa basal ganglia date: 09-13-2019 18:30 gmt revision:6 [5] [4] [3] [2] [1] [0] [head]

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

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

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

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

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

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

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

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

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

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

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

Electrophysiology:

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

STN:

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

GPi:

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

SNr:

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

GPe:

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

SNpc:

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

Synthesis:

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

Parkinson's disease:

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

Huntingtons

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

STN / Hemiballismus

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

Experimental lesions:

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

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

____References____

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

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

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

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

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

PMID-2479133 The functional anatomy of basal ganglia disorders.

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

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

Saccades:

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

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

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

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

My thoughts:

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

____References____

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

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

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

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

____References____

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

____References____

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

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

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

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

____References____

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

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

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

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

____References____

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

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

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

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

____References____

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

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

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

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

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

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

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

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

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

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

____References____

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

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

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

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

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

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

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

____References____

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

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

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

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

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

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

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

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

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

____References____

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

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

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

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

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ref: Elble-1996.03 tags: tremor STN VIM thalamus basal_ganglia Elble Parkinson's ET dyskinesia thalamus VIM DBS date: 01-24-2012 21:19 gmt revision:7 [6] [5] [4] [3] [2] [1] [head]

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

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

____References____

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

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

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

____References____

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

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ref: Parush-2011.01 tags: basal ganglia reinforcement learning hypothesis frontiers israel date: 01-24-2012 04:05 gmt revision:2 [1] [0] [head]

PMID-21603228[0] Dopaminergic Balance between Reward Maximization and Policy Complexity.

  • model complexity discounting is an implicit thing.
    • the basal ganglia aim at optimization of independent gain and cost functions. Unlike previously suggested single-variable maximization processes, this multi-dimensional optimization process leads naturally to a softmax-like behavioral policy
  • In order for this to work:
    • dopamine directly affects striatal excitability and thus provides a pseudo-temperature signal that modulates the tradeoff between gain and cost.

____References____

[0] Parush N, Tishby N, Bergman H, Dopaminergic Balance between Reward Maximization and Policy Complexity.Front Syst Neurosci 5no Issue 22 (2011)

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

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

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

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

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

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

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

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

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

____References____

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

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ref: Boyd-2004.08 tags: basal ganglia learning implicit explicit lesion stroke date: 05-05-2009 23:14 gmt revision:1 [0] [head]

PMID-15286181[0] Providing explicit information disrupts implicit motor learning after basal ganglia stroke.

  • Evidence suggests that the BG is important for advance preparation of responses in learned sequences of actions; when given knowledge about upcoming responses, healthy subjects used the information to prepare for not only their first, but subsequent movements. Individuals with PD only used advanced infor to prepare for the first movement.
  • Interestingly, evidence is accumulating that in some cases conscious strategies for movement disrupts motor learning.
  • The task here was to perform a contiuous tracking task where the middle third segment was constant between trials. (Performance on this segment was what was measured).
  • As the title says, telling the subjects that the middle third does not change (explicit knowledge) impeded their performance relative to uninformed controls. This was not seen in the matched healthy subjects.
  • They looked at improvement in tracking ability, not the ability itself.

____References____

[0] Boyd LA, Winstein CJ, Providing explicit information disrupts implicit motor learning after basal ganglia stroke.Learn Mem 11:4, 388-96 (2004 Jul-Aug)

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ref: Seidler-2006.11 tags: basal ganglia learning fMRI adaptation date: 03-11-2009 21:34 gmt revision:4 [3] [2] [1] [0] [head]

PMID-16794848[9] Bilateral basal ganglia activation associated with sensorimotor adaptation.

  • shows that the basal ganglia is highly active durnig the initial stages of sensory motor adaptation (cursor rotation).
    • specifically: "We observed activation in the right globus pallidus and putamen, along with the right prefrontal, premotor and parietal cortex," to support spatial cognitive processes of adaptation.. and .. "activation in the left globus pallidus and caudate nucleus, along with the left premotor and supplementary motor cortex, which may support the sensorimotor processes of adaptation"
  • human subjects in a 3T MRI scanner; BOLD signal.

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

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

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

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

PMID-18958234 Endocannabinoid Signaling is Critical for Habit Formation.

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

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

PMID-18808769 Modeling the organization of the basal ganglia.

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

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

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

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

____References____

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

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

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

____References____

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

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

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

____References____

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

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

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

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

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

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

____References____

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

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

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

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

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

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

____References____

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ref: Rektor-2003.03 tags: ERP basal ganglia P300 EEG date: 09-25-2008 02:35 gmt revision:2 [1] [0] [head]

PMID-12705427[0] A SEEG study of ERP in motor and premotor cortices and in the basal ganglia.

  • SEEG = stereo (algorithmically (not electrically) differential) EEG.
  • Used depth electrodes in epilepsy patients.
  • targeted M1, SMA & premotor cortices as well as the basal ganglia.
  • ERP larger and more frequent in the basal ganglia, with no difference in the latency between the ERP in the cortex and in the basal ganglia.
  • ERP were in response to visual and auditory 'oddball' tasks
    • Patients had to detect the less usual tone or visual object & count it; sometimes detection involved pressing a button.

____References____

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

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

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

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ref: 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: Wichmann-1999.04 tags: parkinsons basal ganglia substantia nigra date: 0-0-2007 0:0 revision:0 [head]

PMID-10323285 Comparison of MPTP-induced changes in spontaneous neuronal discharge in the internal pallidal segment and in the substania nigra pars reticulata

  • putamen = motor portion of the striatum.
  • basal ganglia output is directed toward the ventral anterior, ventrolateral, and centromedial nuclei of the thalamus, which, in turn, project back to the cortex. Plus, the output of the basal ganglia project to the cortex.
  • MPTP induces excessive 3-8 Hz bursts in the GPi (e.g. correlated with tremor).

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ref: Albin-1989.1 tags: parkinsons basal ganglia 1990 date: 0-0-2007 0:0 revision:0 [head]

PMID-2479133

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

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

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ref: Stefani-1995.09 tags: electrophysiology dopamine basal_ganglia motor learning date: 0-0-2007 0:0 revision:0 [head]

PMID-8539419 Electrophysiology of dopamine D-1 receptors in the basal ganglia: old facts and new perspectives.

  • D1 is inhibitory (modulatory) on striatal neurons.
  • D1 cloned in 1990
  • D1 stimulates adenyl cyclase. (cAMP)
  • D1 activity shown to be necessary, but not sufficient, to generate long-term depression in striatal slices.
  • SKF 38393 was designed as a selective D1 receptor agonist; it has been available since the late 70's; it has nanomolar affinity for D1-R. SKF 38393 inhibits action potential discharge in striatal neurons as measued through response to intracellular current depolarizations.
  • striatal cells project to the substantia nigra.
  • alternate hypothesis: D1 activation on the striatonigral afferents to the ventral tegmental area (VTA) promotes GABA release.
    • recall that the VTA projects to the frontal/prefrontal cortex (PFC) via the mesocortical dopiminergic pathway. http://grad.uchc.edu/phdfaculty/antic.html There, DA synapese on spines of distal dendrites in juxtaposition with glutamergic synapses. this guy posits that these DA synapses are involved in the pathology of schizophrenia, and he uses optical techniques to measure the DA/Glu synapses.
    • VTA is just below the red nucleus in rats.
  • some people report that SKF 38393 potentiated depolarizing membrane responses to exogenous NMDA (agonist, excitotoxin).
  • they prefer the magnesium-dependent LTD pathway.
    • D1 receptor antagonist SCH 23390 prevented the generation of LTD in striatum. (Calabresi et al 1992).
    • in DA-depleted slices, LTD could be restored by the co-administration of D1 and D2 agonists.

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

Title: Error signals in the cortex and basal ganglia.

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