Long-term subthalamic nucleus stimulation improves sensorimotor integration and proprioception

Shukla, Aparna Wagle; Moro, Elena; Gunraj, Carolyn; Lozano, Andrés M.; Hodaie, Mojgan; Lang, Anthony E.; Chen, Robert

doi:10.1136/jnnp-2012-304102

Cited by 45 publications

(25 citation statements)

References 39 publications

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“…Preliminary data showing that sensorimotor cortex plasticity improves only after long-term synergistic combination of DBS with reduced doses of levodopa, but not after DBS alone (141). That long-term stimulation is required for restoring sensory afferent inhibition of M1(142) indicates that cerebellar control of sensory processing may also normalize only after chronic stimulation of STN.Does selective DBS of the ventral GPi but not of the dorsal GPi or STN simultaneously inhibit the propagation of pro-dyskinetic signals through both cortico-striatal synapses and cerebello-striatal synapses (relayed through CM/PF thalamic nuclei) on D1-bearing MSNs? It is already known that GPi has functional somatotopy (143) and that ventral GPi stimulation has anti-dyskinetic effects while dorsal GPi stimulation improves akinesia and induces dyskinesias (144).…”

Section: Proposed Model Of Parkinsonism and Levodopa-induced Dyskinesmentioning

confidence: 99%

Section: Proposed Model Of Parkinsonism and Levodopa-induced Dyskinesmentioning

confidence: 99%

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Cerebellum in Levodopa-Induced Dyskinesias: The Unusual Suspect in the Motor Network

Kishore

Popa

2014

Front. Neurol.

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The exact mechanisms that generate levodopa-induced dyskinesias (LID) during chronic levodopa therapy for Parkinson’s disease (PD) are not yet fully established. The most widely accepted theories incriminate the non-physiological synthesis, release and reuptake of dopamine generated by exogenously administered levodopa in the striatum, and the aberrant plasticity in the cortico-striatal loops. However, normal motor performance requires the correct recruitment of motor maps. This depends on a high level of synergy within the primary motor cortex (M1) as well as between M1 and other cortical and subcortical areas, for which dopamine is necessary. The plastic mechanisms within M1, which are crucial for the maintenance of this synergy, are disrupted both during “OFF” and dyskinetic states in PD. When tested without levodopa, dyskinetic patients show loss of treatment benefits on long-term potentiation and long-term depression-like plasticity of the intracortical circuits. When tested with the regular pulsatile levodopa doses, they show further impairment of the M1 plasticity, such as inability to depotentiate an already facilitated synapse and paradoxical facilitation in response to afferent input aimed at synaptic inhibition. Dyskinetic patients have also severe impairment of the associative, sensorimotor plasticity of M1 attributed to deficient cerebellar modulation of sensory afferents to M1. Here, we review the anatomical and functional studies, including the recently described bidirectional connections between the cerebellum and the basal ganglia that support a key role of the cerebellum in the generation of LID. This model stipulates that aberrant neuronal synchrony in PD with LID may propagate from the subthalamic nucleus to the cerebellum and “lock” the cerebellar cortex in a hyperactive state. This could affect critical cerebellar functions such as the dynamic and discrete modulation of M1 plasticity and the matching of motor commands with sensory information from the environment during motor performance. We propose that in dyskinesias, M1 neurons have lost the ability to depotentiate an activated synapse when exposed to acute pulsatile, non-physiological, dopaminergic surges and become abnormally receptive to unfiltered, aberrant, and non-salient afferent inputs from the environment. The motor program selection in response to such non-salient and behaviorally irrelevant afferent inputs would be abnormal and involuntary. The motor responses are worsened by the lack of normal subcortico–cortical inputs from cerebellum and basal ganglia, because of the aberrant plasticity at their own synapses. Artificial cerebellar stimulation might help re-establish the cerebellar and basal ganglia control over the non-salient inputs to the motor areas during synaptic dopaminergic surges.

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Section: Proposed Model Of Parkinsonism and Levodopa-induced Dyskinesmentioning

confidence: 99%

Section: Proposed Model Of Parkinsonism and Levodopa-induced Dyskinesmentioning

confidence: 99%

Cerebellum in Levodopa-Induced Dyskinesias: The Unusual Suspect in the Motor Network

Kishore

Popa

2014

Front. Neurol.

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“…[64] In a subsequent longitudinal study these modulatory effects of STN DBS were demonstrated only at six months and not at one month, these findings suggested chronic stimulation is important in elicitation and potentially maintenance of physiological changes. [ • 65]…”

Section: Tms In Parkinson’s Diseasementioning

confidence: 99%

Treatment and Physiology in Parkinson’s Disease and Dystonia: Using Transcranial Magnetic Stimulation to Uncover the Mechanisms of Action

Shukla

Vaillancourt

2014

Curr Neurol Neurosci Rep

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Transcranial magnetic stimulation (TMS) has served as an important technological breakthrough in the field of movement disorders physiology over the last three decades. TMS has grown popular due to the ease of application as well as its painless and noninvasive character. The technique has shed important insights into understanding the pathophysiology of movement disorders particularly Parkinson’s disease and dystonia. The basic applications have included the study of motor cortex excitability, functioning of excitatory and inhibitory circuits, study of interactions between sensory and motor systems, and the plasticity response of the brain. TMS has also made important contributions in understanding response to treatments such as the dopaminergic medications, botulinium toxin injections and deep brain stimulation surgery. This review summarizes the knowledge gained to date with TMS in Parkinson’s disease and dystonia and highlights the current challenges in utilization of TMS technology.

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“…On the other hand, LAI is 524 reduced in PD and is unaffected by medications (Sailer et al, 525 2003). SAI and LAI normalized with STN-DBS in PD patients (Sailer 526 et al, 2007;Wagle Shukla et al, 2013). Thus, the effects of STN-527 DBS are not always the same as dopaminergic mediations as 528 dopaminergic medications reduced SAI, which was normalized by 529 DBS (Sailer et al, 2002).…”

mentioning

confidence: 91%

The mechanisms of action of deep brain stimulation and ideas for the future development

Udupa

Chen

2015

Progress in Neurobiology

129

133

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Long-term subthalamic nucleus stimulation improves sensorimotor integration and proprioception

Abstract: Chronic STN DBS in PD normalises sensorimotor integration and proprioception, likely through long-term plastic changes in the basal ganglia thalamocortical circuit.

Cited by 45 publications

References 39 publications

Cerebellum in Levodopa-Induced Dyskinesias: The Unusual Suspect in the Motor Network

Cerebellum in Levodopa-Induced Dyskinesias: The Unusual Suspect in the Motor Network

Treatment and Physiology in Parkinson’s Disease and Dystonia: Using Transcranial Magnetic Stimulation to Uncover the Mechanisms of Action

The mechanisms of action of deep brain stimulation and ideas for the future development

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