Cerebellum and Cortical Plasticity: the Case of Dystonia

Purpose

- Objective : Sensorimotor adaptation allows the modification of the motor command taking into account the errors detected during execution of prior movements. It involves a large cortico-subcortical network. Isolated lesions of this network do not systematically alter sensorimotor adaptation except for cerebellar lesions. The cerebellum is thus a key structure for sensorimotor adaptation. However, the link between cerebellar and the cortical plasticity underlying sensorimotor adaptation remain unknown. Alteration of sensorimotor adaptation is associated with dystonia but it is unclear whether it is a cause or consequence of dystonia. It has been hypothesized that the abnormal plasticity observed in dystonia could account for the associated alteration of sensorimotor adaptation.

Classically, basal ganglia dysfunction is considered to be crucial for dystonia pathogenesis. However, recent studies suggest that the involvement of the cerebellum may also be important in this setting. In primary dystonia, imaging studies showed abnormal cerebellar activation during sensorimotor adaptation tasks and neurophysiological studies demonstrated a decrease of cerebellar output.

The aim of this study is to investigate the role of the cerebellum in the cortical plasticity underlying sensorimotor adaptation both in healthy subjects (normal plasticity) and in dystonic patients (abnormal plasticity).

- Methods: Paired associative stimulation PAS consists in repetitive pairing of a peripheral nerve and a cortical stimulation. This kind of stimulation has been designed to induce artificial plasticity that can be easily measured. This PAS induced sensorimotor plasticity is exacerbated and has lost its topographical specificity in dystonic patients.TMS using trains of TMS pulses (rTMS) can be applied on the cerebellum to modulate its output. We will test the effect of rTMS induced modulation (cTBS- inhibitory, iTBS-excitatory, sham) of the cerebellar output on PAS induced plasticity in patients with dystonia and healthy control.

We will also assess the acute effect of the rTMS induced modulation of the cerebellar output on the dystonic symptoms and on the performance at a validated sensorimotor adaptation task. This will be done by double blind post-hoc scoring of the dystonia (BFM or TWSTRS) on standardized videorecording and measurement of the performance at the task after each rTMS session (cTBS, iTBS, sham).

Finally, we will assess the variation of PAS effect on other parameters reflecting cortical excitability after each rTMS session (cTBS, iTBS, sham).


Eligibility Criteria:
Inclusion criteria

All subjects

* Age \>18 years and \< 70 years
* Normal physical and neurological examination, except for dystonia (when present)
* No treatment with botulinum toxin during the last three months
* No treatment altering the cortical excitability
* Agreement to use a medically acceptable method of contraception throughout the study for female of childbearing potential

Primary focal dystonia group

* Patients with cervical and/or upper limb dystonia
* No cause of secondary dystonia

Secondary dystonia group

• Cervical dystonia and/or upper limb dystonia History of perinatal anoxia

Exclusion criteria

* MMS ≤ 24/30
* Current neurological or psychiatric illness other than dystonia.
* Individual who is on medication which is known to lower seizure threshold (see lists above), or who has a pacemaker, an implanted medical pump, a metal plate, a metal plate or metal object in the skull or eye (for example after brain surgery) will be excluded
* Uncontrollable medical problems not related to dystonia such as; cardiopulmonary disease, severe rheumatoid arthritis, active joint deformity of arthritic origin, active cancer, or renal disease
* Previous history of seizure(s) or current active epilepsy
* Pregnancy, breast feeding women and women who are of childbearing age and not practicing adequate birth control.
* Patients legally protected
* Patients who are not enrolled at social security