Loss of Specificity in Basal Ganglia Related Movement Disorders

Bronfeld, Maya; Bar‐Gad, Izhar

doi:10.3389/fnsys.2011.00038

Cited by 32 publications

(31 citation statements)

References 150 publications

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“…For example, dystonia shares many physiologic features with PD. Both disorders exhibit enhanced neuronal oscillations, synchrony, and burst-firing in the STN[124]andGPi[105,125–127]. Thus,noneofthese changes in and of themselves can drive parkinsonism.…”

Section: Discussionmentioning

confidence: 99%

“…Related to synchrony is the loss of specificity of BG neurons for passive and active movement [105]. The proportion of neurons with firing rate changes during movement is larger in MPTP treated monkeys compared to controls [106], and an increased proportion of BG and thalamic neurons encode for movement about multiple joints [62, 107].…”

Section: Electrophysiological Changes In Animal Models Of Pdmentioning

confidence: 99%

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Review: Electrophysiology of Basal Ganglia and Cortex in Models of Parkinson Disease

Ellens

Leventhal

2013

Journal of Parkinson's Disease

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Incomplete understanding of the systems-level pathophysiology of Parkinson Disease (PD) remains a significant barrier to improving its treatment. Substantial progress has been made, however, due to the availability of neurotoxins that selectively target monoaminergic (in particular, dopaminergic) neurons. This review discusses the in vivo electrophysiology of basal ganglia (BG), thalamic, and cortical regions after dopamine-depleting lesions. These include firing rate changes, neuronal burst-firing, neuronal oscillations, and neuronal synchrony that result from a combination of local microanatomic changes and network-level interactions. While much is known of the clinical and electrophysiological phenomenology of dopamine loss, a critical gap in our conception of PD pathophysiology is the link between them. We discuss potential mechanisms by which these systems-level electrophysiological changes may emerge, as well as how they may relate to clinical parkinsonism. Proposals for an updated understanding of BG function are reviewed, with an emphasis on how emerging frameworks will guide future research into the pathophysiology and treatment of PD.

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Section: Discussionmentioning

confidence: 99%

Section: Electrophysiological Changes In Animal Models Of Pdmentioning

confidence: 99%

Review: Electrophysiology of Basal Ganglia and Cortex in Models of Parkinson Disease

Ellens

Leventhal

2013

Journal of Parkinson's Disease

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“…22 There is evidence to suggest that basal ganglia dysfunction in PD leads to a loss of specificity of surviving neurons and their connected structures. 23 Such changes could alter the precise coupling between sensory inputs and motor outputs that is characteristic of motor cortex. Since PAS relies on the interaction between sensory afferents and motor out- Abbreviations: ADM ϭ abductor digiti minimi; APB ϭ abductor pollicis brevis; PAS ϭ paired associative stimulation.…”

Section: Resultsmentioning

confidence: 99%

Functional reorganization of sensorimotor cortex in early Parkinson disease

et al. 2012

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Objective: Compensatory reorganization of the nigrostriatal system is thought to delay the onset of symptoms in early Parkinson disease (PD). Here we sought evidence that compensation may be a part of a more widespread functional reorganization in sensorimotor networks, including primary motor cortex. Methods:Several neurophysiologic measures known to be abnormal in the motor cortex (M1) of patients with advanced PD were tested on the more and less affected side of 16 newly diagnosed and drug-naive patients with PD and compared with 16 age-matched healthy participants. LTP-like effects were probed using a paired associative stimulation protocol. We also measured short interval intracortical inhibition, intracortical facilitation, cortical silent period, and input/output curves. Results:The less affected side in patients with PD had preserved intracortical inhibition and a larger response to the plasticity protocol compared to healthy participants. On the more affected side, there was no response to the plasticity protocol and inhibition was reduced. There was no difference in input/output curves between sides or between patients with PD and healthy participants. Conclusions:Increased motor cortical plasticity on the less affected side is consistent with a functional reorganization of sensorimotor cortex and may represent a compensatory change that contributes to delaying onset of clinical symptoms. Alternatively, it may reflect a maladaptive plasticity that provokes symptom onset. Plasticity deteriorates as the symptoms progress, as seen on the more affected side. The rate of change in paired associative stimulation response over time could be developed into a surrogate marker of disease progression in PD. Neurology ® 2012;78:1441-1448 GLOSSARY ADM ϭ abductor digiti minimi; AMT ϭ active motor threshold; APB ϭ abductor pollicis brevis; CS ϭ conditioning stimulus; CSP ϭ cortical silent period; DaT ϭ dopamine transporter; I/O ϭ input/output; ICF ϭ intracortical facilitation; ISI ϭ interstimulus interval; LTP ϭ long-term potentiation; MEP ϭ motor evoked potential; PAS ϭ paired associative stimulation; PD ϭ Parkinson disease; RMT ϭ resting motor threshold; SICI ϭ short-latency intracortical inhibition; TMS ϭ transcranial magnetic stimulation; UPDRS ϭ Unified Parkinson's Disease Rating Scale.Motor signs in Parkinson disease (PD) appear when striatal dopamine is depleted beyond a critical threshold of ϳ60%-80%.1 Neuropathologic and neuroimaging evidence suggests that presynaptic and synaptic changes in the nigrostriatal system compensate for dopamine deficiency.1-6 Indeed, given the extent of preclinical dopaminergic denervation, 7 it is conceivable that compensatory changes extend also beyond the nigrostriatal portion of the motor circuit.Patients with clinically asymmetric PD represent a valuable model to study compensatory reorganization within the motor system since functional changes that prevent motor symptom progression are likely to be more evident on the less affected side. A previous [ 18 F]-fluorodeo...

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“…Focal microinjections of the GABA-A antagonist bicuculline in the striatum lead to loss of specificity (LOS) in BG firing patterns (Bronfeld and Bar-Gad, 2011) and cause repetitive motor tics confined to a single or a few muscles (McCairn et al, 2009). Bronfeld and Bar-Gad (2011) showed that LOS actually is a general phenomenon in BG movement disorders, including PD.…”

Section: Introductionmentioning

confidence: 99%

“…Bronfeld and Bar-Gad (2011) showed that LOS actually is a general phenomenon in BG movement disorders, including PD. The activity of the projection neurons (∼95%) in the striatum, the medium spiny neuron (MSN), is controlled by, e.g., recurrent inhibition and feed-forward inhibition from fast spiking neurons (FSNs).…”

Section: Introductionmentioning

confidence: 99%

Untangling Basal Ganglia Network Dynamics and Function: Role of Dopamine Depletion and Inhibition Investigated in a Spiking Network Model

Lindahl

Kotaleski

2016

eNeuro

109

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The basal ganglia are a crucial brain system for behavioral selection, and their function is disturbed in Parkinson’s disease (PD), where neurons exhibit inappropriate synchronization and oscillations. We present a spiking neural model of basal ganglia including plausible details on synaptic dynamics, connectivity patterns, neuron behavior, and dopamine effects. Recordings of neuronal activity in the subthalamic nucleus and Type A (TA; arkypallidal) and Type I (TI; prototypical) neurons in globus pallidus externa were used to validate the model. Simulation experiments predict that both local inhibition in striatum and the existence of an indirect pathway are important for basal ganglia to function properly over a large range of cortical drives. The dopamine depletion–induced increase of AMPA efficacy in corticostriatal synapses to medium spiny neurons (MSNs) with dopamine receptor D2 synapses (CTX-MSN D2) and the reduction of MSN lateral connectivity (MSN–MSN) were found to contribute significantly to the enhanced synchrony and oscillations seen in PD. Additionally, reversing the dopamine depletion–induced changes to CTX–MSN D1, CTX–MSN D2, TA–MSN, and MSN–MSN couplings could improve or restore basal ganglia action selection ability. In summary, we found multiple changes of parameters for synaptic efficacy and neural excitability that could improve action selection ability and at the same time reduce oscillations. Identification of such targets could potentially generate ideas for treatments of PD and increase our understanding of the relation between network dynamics and network function.

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Loss of Specificity in Basal Ganglia Related Movement Disorders

Cited by 32 publications

References 150 publications

Review: Electrophysiology of Basal Ganglia and Cortex in Models of Parkinson Disease

Review: Electrophysiology of Basal Ganglia and Cortex in Models of Parkinson Disease

Functional reorganization of sensorimotor cortex in early Parkinson disease

Untangling Basal Ganglia Network Dynamics and Function: Role of Dopamine Depletion and Inhibition Investigated in a Spiking Network Model

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