Metabolic changes induced by theta burst stimulation of the cerebellum in dyskinetic Parkinson’s disease patients

Brusa, Livia; Ceravolo, Roberto; Kiferle, Lorenzo; Monteleone, Fabrizia; Iani, Cesare; Schillaci, Orazio; Stanzione, Paolo; Koch, Giacomo

doi:10.1016/j.parkreldis.2011.08.019

Cited by 57 publications

(46 citation statements)

References 29 publications

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“…Other authors have proposed that the cerebellum is itself an important site of maladaptive plasticity in both PD and LID. According to this view, increased cerebellar activity would be a compensatory response to an altered processing of movement-related information in striato-thalamo-cortical circuits, and robust plastic responses in the cerebellum would increase the likelihood to develop LID (Brusa et al 2012; Koch et al 2009). …”

Section: Role Of the Cerebellummentioning

confidence: 99%

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On the neuronal circuitry mediating l-DOPA-induced dyskinesia

2018

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With the advent of rodent models of l-DOPA-induced dyskinesia (LID), a growing literature has linked molecular changes in the striatum to the development and expression of abnormal involuntary movements. Changes in information processing at the striatal level are assumed to impact on the activity of downstream basal ganglia nuclei, which in turn influence brain-wide networks, but very little is actually known about systems-level mechanisms of dyskinesia. As an aid to approach this topic, we here review the anatomical and physiological organisation of cortico-basal ganglia-thalamocortical circuits, and the changes affecting these circuits in animal models of parkinsonism and LID. We then review recent findings indicating that an abnormal cerebellar compensation plays a causal role in LID, and that structures outside of the classical motor circuits are implicated too. In summarizing the available data, we also propose hypotheses and identify important knowledge gaps worthy of further investigation. In addition to informing novel therapeutic approaches, the study of LID can provide new clues about the interplay between different brain circuits in the control of movement.

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Section: Role Of the Cerebellummentioning

confidence: 99%

“…There is circumstantial evidence of increased cerebellar compensation in LID, as suggested by finding of increased metabolic activity in the deep cerebellar nuclei (Brusa et al 2012) and in the red nucleus (Lewis et al 2013), which is an important projection target of the deep cerebellar nuclei.…”

Section: Role Of the Cerebellummentioning

confidence: 99%

On the neuronal circuitry mediating l-DOPA-induced dyskinesia

2018

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“…Investigations aimed at modelling the DCS electric field in humans demonstrated that maximal activation was localised to the targeted cerebellar hemisphere [54]. In contrast, repetitive TMS protocols in Parkinson's disease patients were found to alter metabolic activity in both cerebellar cortex and the deep cerebellar nuclei [55]. Similarly, cerebellar DCS does not alter the excitability of M1 to single pulse TMS, while cerebellar repetitive TMS increased the MEP response [56].…”

Section: Non-invasive Cerebellar Stimulationmentioning

confidence: 99%

Anodal Direct Current Stimulation of the Cerebellum Reduces Cerebellar Brain Inhibition but Does Not Influence Afferent Input from the Hand or Face in Healthy Adults

2015

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“…In patients with PD, with mild to moderate LID, repeated sessions of bilateral cerebellar inhibitory stimulation after regular doses of levodopa induce a sustained reduction of dyskinesia lasting at least 2 weeks (30, 129). Repeated cerebellar stimulation can also reduce the cerebellar cortical activity and enhance dentate nuclear activity in imaging studies in PD patients with dyskinesias (130). In such patients, a single session of inhibitory stimulation of the cerebellar cortex combined with levodopa can restore the sensorimotor plasticity tested by PAS, but not the local intracortical plasticity as tested with TBS (30).…”

Section: Cerebellar Link To Motor Circuits In Health Parkinsonism Anmentioning

confidence: 99%

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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Metabolic changes induced by theta burst stimulation of the cerebellum in dyskinetic Parkinson’s disease patients

Cited by 57 publications

References 29 publications

On the neuronal circuitry mediating l-DOPA-induced dyskinesia

On the neuronal circuitry mediating l-DOPA-induced dyskinesia

Anodal Direct Current Stimulation of the Cerebellum Reduces Cerebellar Brain Inhibition but Does Not Influence Afferent Input from the Hand or Face in Healthy Adults

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

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