Browsing by Author "Meunier, S"

Now showing 1 - 9 of 9
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    Abnormal cerebellar processing of the neck proprioceptive information drives dysfunctions in cervical dystonia.
    (Sci Rep. 2018, 2018-02) Popa, T; Hubsch, C; James, P; Richard, A; Russo, M; Pradeep, S; Krishan, S; Roze, E; Meunier, S; Kishore, A
    The cerebellum can influence the responsiveness of the primary motor cortex (M1) to undergo spike timing-dependent plastic changes through a complex mechanism involving multiple relays in the cerebello-thalamo-cortical pathway. Previous TMS studies showed that cerebellar cortex excitation can block the increase in M1 excitability induced by a paired-associative stimulation (PAS), while cerebellar cortex inhibition would enhance it. Since cerebellum is known to be affected in many types of dystonia, this bidirectional modulation was assessed in 22 patients with cervical dystonia and 23 healthy controls. Exactly opposite effects were found in patients: cerebellar inhibition suppressed the effects of PAS, while cerebellar excitation enhanced them. Another experiment comparing healthy subjects maintaining the head straight with subjects maintaining the head turned as the patients found that turning the head is enough to invert the cerebellar modulation of M1 plasticity. A third control experiment in healthy subjects showed that proprioceptive perturbation of the sterno-cleido-mastoid muscle had the same effects as turning the head. We discuss these finding in the light of the recent model of a mesencephalic head integrator. We also suggest that abnormal cerebellar processing of the neck proprioceptive information drives dysfunctions of the integrator in cervical dystonia.
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    Age-related decline in the responsiveness of motor cortex to plastic forces reverses with levodopa or cerebellar stimulation
    (Neurobiology of aging, 2014-11) Kishore, A; Popa, T; James, P; Yahia-Cherif, L; Backer, F; Varughese, CL; Govind, P; Pradeep, S; Meunier, S
    The plasticity of motor cortex is integral for motor memory and skills acquisition but it declines with aging. Forty healthy volunteers, across 6 decades, were tested to examine the (a) age-dependency of motor cortex responsiveness to plasticity induction, as measured from the response to paired associative stimulation (PAS) and the (b) effect of aging on the cerebellar modulation of motor cortex response to PAS. We examined if reduced dopaminergic transmission was involved in the age-related decline of response to PAS by retesting 10 of the older subjects after a single dose of levodopa. There was a substantial decline in the motor cortex response to PAS with aging, which was restored by levodopa in the older subjects. The cerebellar modulation of motor cortex response to PAS was less vulnerable to aging and a single session of cerebellar inhibition reinstated the cortical responsiveness in older subjects. Both levodopa and cerebellar inhibition can be tested for their ability to enhance motor skills acquisition and motor performance in the elderly individuals.
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    Cerebellar influence on motor cortex plasticity: behavioral implications for Parkinson's disease
    (FRONTIERS IN NEUROLOGY, 2014) Kishore, A; Meunier, S; Popa, T
    Normal motor behavior involves the creation of appropriate activity patterns across motor networks, enabling firing synchrony, synaptic integration, and normal functioning of these networks. Strong topography-specific connections among the basal ganglia, cerebellum, and their projections to overlapping areas in the motor cortices suggest that these networks could influence each other's plastic responses and functions. The defective striatal signaling in Parkinson's disease (PD) could therefore lead to abnormal oscillatory activity and aberrant plasticity at multiple levels within the interlinked motor networks. Normal striatal dopaminergic signaling and cerebellar sensory processing functions influence the scaling and topographic specificity of M1 plasticity. Both these functions are abnormal in PD and appear to contribute to the abnormal M1 plasticity. Defective motor map plasticity and topographic specificity within M1 could lead to incorrect muscle synergies, which could manifest as abnormal or undesired movements, and as abnormal motor learning in PD. We propose that the loss of M1 plasticity in PD reflects a loss of co-ordination among the basal ganglia, cerebellar, and cortical inputs which translates to an abnormal plasticity of motor maps within M1 and eventually to some of the motor signs of PD. The initial benefits of dopamine replacement therapy on M1 plasticity and motor signs are lost during the progressive course of disease. Levodopa-induced dyskinesias in patients with advanced PD is linked to a loss of M1 sensorimotor plasticity and the attenuation of dyskinesias by cerebellar inhibitory stimulation is associated with restoration of M1 plasticity. Complimentary interventions should target reestablishing physiological communication between the striatal and cerebellar circuits, and within striato-cerebellar loop. This may facilitate correct motor synergies and reduce abnormal movements in PD.
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    Cerebellar Processing of Sensory Inputs Primes Motor Cortex Plasticity
    (CEREBRAL CORTEX, 2013) Popa, T; Velayudhan, B; Hubsch, C; Pradeep, S; Roze, E; Vidailhet, M; Meunier, S; Kishore, A
    Plasticity of the human primary motor cortex (M1) has a critical role in motor control and learning. The cerebellum facilitates these functions using sensory feedback. We investigated whether cerebellar processing of sensory afferent information influences the plasticity of the primary motor cortex (M1). Theta-burst stimulation protocols (TBS), both excitatory and inhibitory, were used to modulate the excitability of the posterior cerebellar cortex and to condition an ongoing M1 plasticity. M1 plasticity was subsequently induced in 2 different ways: by paired associative stimulation (PAS) involving sensory processing and TBS that exclusively involves intracortical circuits of M1. Cerebellar excitation attenuated the PAS-induced M1 plasticity, whereas cerebellar inhibition enhanced and prolonged it. Furthermore, cerebellar inhibition abolished the topography-specific response of PAS-induced M1 plasticity, with the effects spreading to adjacent motor maps. Conversely, cerebellar excitation had no effect on the TBS-induced M1 plasticity. This demonstrates the key role of the cerebellum in priming M1 plasticity, and we propose that it is likely to occur at the thalamic or olivo-dentate nuclear level by influencing the sensory processing. We suggest that such a cerebellar priming of M1 plasticity could shape the impending motor command by favoring or inhibiting the recruitment of several muscle representations.
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    Cerebellar Sensory Processing Alterations Impact Motor Cortical Plasticity in Parkinson's Disease: Clues from Dyskinetic Patients
    (Cereb. Cortex (2013), 2013-04) Kishore, A; Popa, T; Balachandran, A; Chandran, S; Pradeep, S; Backer, F; Krishnan, S; Meunier, S
    The plasticity of primary motor cortex (M1) in patients with Parkinson's disease (PD) and levodopa-induced dyskinesias (LIDs) is severely impaired. We recently reported in young healthy subjects that inhibitory cerebellar stimulation enhanced the sensorimotor plasticity of M1 that was induced by paired associative stimulation (PAS). This study demonstrates that the deficient sensorimotor M1 plasticity in 16 patients with LIDs could be reinstated by a single session of real inhibitory cerebellar stimulation but not sham stimulation. This was evident only when a sensory component was involved in the induction of plasticity, indicating that cerebellar sensory processing function is involved in the resurgence of M1 plasticity. The benefit of inhibitory cerebellar stimulation on LIDs is known. To explore whether this benefit is linked to the restoration of sensorimotor plasticity of M1, we conducted an additional study looking at changes in LIDs and PAS-induced plasticity after 10 sessions of either bilateral, real inhibitory cerebellar stimulation or sham stimulation. Only real and not sham stimulation had an antidyskinetic effect and it was paralleled by a resurgence in the sensorimotor plasticity of M1. These results suggest that alterations in cerebellar sensory processing function, occurring secondary to abnormal basal ganglia signals reaching it, may be an important element contributing to the maladaptive sensorimotor plasticity of M1 and the emergence of abnormal involuntary movements.
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    Defective cerebellar control of cortical plasticity in writer's cramp
    (Brain., 2013-07) Hubsch, C; Roze, E; Popa, T; Russo, M; Balachandran, A; Pradeep, S; Mueller, F; Brochard, V; Quartarone, A; Degos, B; Vidailhet, M; Kishore, A; Meunier, S
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    Motor cortex plasticity can indicate vulnerability to motor fluctuation and high L-DOPA need in drug-naïve Parkinson's disease.
    (Parkinsonism Relat Disord., 2016-12) Kishore, A; James, P; Krishnan, S; Yahia-Cherif, L; Meunier, S; Popa, T
    Introduction: Motor cortex plasticity is reported to be decreased in Parkinson's disease in studies which pooled patients in various stages of the disease. Whether the early decrease in plasticity is related to the motor signs or is linked to the future development of motor complications of treatment is unclear. The aim of the study was to test if motor cortex plasticity and its cerebellar modulation are impaired in treatment-naïve Parkinson's disease, are related to the motor signs of the disease and predict occurrence of motor complications of treatment. Methods: Twenty-nine denovo patients with Parkinson's disease were longitudinally assessed for motor complications for four years. Using transcranial magnetic stimulation, the plasticity of the motor cortex and its cerebellar modulation were measured (response to paired-associative stimulation alone or preceded by 2 active cerebellar stimulation protocols), both in the untreated state and after a single dose of L-DOPA. Twenty-six matched, healthy volunteers were tested, only without L-DOPA. Results: Patients and healthy controls had similar proportions of responders and non-responders to plasticity induction. In the untreated state, the more efficient was the cerebellar modulation of motor cortex plasticity, the lower were the bradykinesia and rigidity scores. The extent of the individual plastic response to paired associative stimulation could indicate a vulnerability to develop early motor fluctuation but not dyskinesia. Conclusions: Measuring motor cortex plasticity in denovo Parkinson's disease could be a neurophysiological parameter that may help identify patients with greater propensity for early motor fluctuations.
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    Severity of Writer's Cramp is Related to Faulty Motor Preparation
    (Cereb Cortex, 2017-09) Kishore, A; Popa, T; James, P; Krishnan, S; Robert, S; Meunier, S
    We characterized, in 37 writer's cramp (WC) patients and 14 healthy volunteers (HV), the buildup of motor representations contralateral ("intended") and ispsilateral ("unintended") to the movement to be produced and the excitability changes in left primary motor cortex during the early reaction time (RT) of a pre-cued reaching movement to pick up a pen with either hand to write. We also tested the excitability of interhemispheric pathways from right dorsal premotor and motor cortices to left motor cortex. During early RT (1) the motor cortex excitability of unintended muscle representations did not decrease in patients as in HV and (2) the connection from the contralateral dorsal premotor cortex to the "intended" motor representation did not function in patients. In HV, the efficiency of intracortical GABA-ergic circuits at rest predicted the degree of excitability changes in the intended motor representation in the early RT. This was not true in patients who had lower efficiency of GABA-ergic circuits. Interestingly, the more severe was the writing impairment, the higher was the level of excitability in the intended and unintended motor representations. It demonstrates, for the first time, that abnormal motor preparation influences the severity of the writing impairment in WC patients.