Multimodal investigation of cerebello-thalamo-cortical connectivity in cervical dystonia

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Dystonia is a movement disorders characterized by sustained or intermittent muscle contractions leading to abnormal postures or movements or both. In Germany about 160.000 people are affected by dystonia. According to the clinical distribution it may be classified into focal, segmental, multifocal, generalized dystonia or hemidystonia. Cervical dystonia (CD) with abnormal postures and movements of the head and neck is the most frequent form of focal dystonias. CD is frequently associated with pain, depression, social stigmatization, secondary degenerative disorders especially of the cervical spine and impaired quality of life. A large body of evidence points to a role of basalganglia-thalamo-cortical dysfunction in the pathophysiology of dystonia. In recent years though, several brain imaging as well as neurophysiological studies suggested that the cerebellum also has a substantial contribution to the pathophysiology of the disease. Consequently, it has been proposed that dystonia is a network disorder involving basal ganglia and cerebellum. In the present study, we aim to assess excitability and connectivity of the cerebello-thalamo-cortical network in relation to motor symptom severity in CD patients. We hypothesize that in CD patients, structural connectivity of the cerebello-thalamo-cortical tract is impaired and excitability of the primary motor cortex (M1) and cerebellum is altered.A group of CD patients will be examined in a multimodal, multi-session study. The study comprises a standardized clinical examination and video-based movement analyses, a neurophysiological examination of sensorimotor excitability with transcranial magnetic stimulation (TMS), modulation of cerebellar excitability with transcranial direct current stimulation (tDCS) and investigation of structural cerebello-thalamo-cortical connectivity with magnetic resonance imaging (MRI). In each session, TMS will be applied to assess sensorimotor and intracortical excitability of M1 with paradigms that are known to reflect increased excitability of the motor system in dystonia patients. To modulate cerebellar excitability either facilitatory, inhibitory or sham tDCS will be applied in a randomised order on three separate days. The impact of cerebellar tDCS on motor cortex excitability and on motor symptom severity will be investigated. Diffusion tensor imaging will be used to investigate properties of the cerebello-thalamo-cortical network. Structural fibre connectivity of the cerebello-thalamo-cortical tract will be assessed and the relation to individual responsiveness to cerebellar tDCS examined.