Thesis defense Britt S. Holland (Donders series 302)

22 March 2018

Promotor: prof. dr. B. Bloem,       
copromotors: dr. B. van de Warrenburg, prof. dr. M. Edwards

Investigating the role of the cerebellum in idiopathic focal dystonia

Dystonia is a disabling movement disorder. In this thesis the contribution of the cerebellum to the pathophysiological processes in dystonia was investigated. Eyeblink classical conditioning (EBCC), a neurophysiological indicator of cerebellar dysfunction, is often abnormal in patients with idiopathic focal dystonia. EBCC could be improved in idiopathic cervical dystonia by practice (via repeated sessions of EBCC) and by direct non-invasive modulation of cerebellar excitability (through inhibitory cTBS). This points to a (partly) functional and reversible disruption of cerebellar functioning.

Abnormal sensorimotor adaptation was demonstrated with a split-belt treadmill walking paradigm in patients, indicating that cerebellar dysfunction in idiopathic focal dystonia extends beyond more pure forms of cerebellum-dependent associative motor learning. Also, a different abnormality, in degree and area, of cerebellar malfunctioning in various forms of idiopathic focal dystonia argues against uniform cerebellar pathology as the main driver.

During an fMRI motor learning study, increased cerebellar activation was beneficial to sequence learning performance in idiopathic cervical dystonia and could therefore serve as a compensatory mechanism. Cerebellar hyperactivity and reduced basal ganglia activation were however not static features of motor control and learning in idiopathic focal dystonia, but dynamic phenomena that can individually exist depending on the functional demands of a motor task. The roles of the cerebellum and basal ganglia in dystonia are thus more complicated than simply a loss or gain of function.

This thesis outlined the current evidence that explores a possible role for the cerebellum in idiopathic focal dystonia in this thesis. It provided additional new insights, but more studies are warranted to further dissect the role of the cerebellum in this movement disorder.