Research over the last decade has refined our understanding of the neuroanatomical
substrates of dystonia. In addition to basal ganglia dysfunction a much wider sensorimotor
network has been implicated and within this network the cerebellum is heralded as a core
node. Much of the literature linking the cerebellum to dystonia consists of cases in which
lesions of the cerebellum are linked to abnormal posture or indirect experimental
associations (reviewed in chapter 1). Better defining the functional role of the cerebellum in
the pathophysiology of dystonia could provide a scientific rational for future therapeutic
advances, adding further weight to an early neurosurgical literature which advocates
targeting the cerebellum and its outflow tracts.
Within this thesis I applied experimental techniques from which direct inferences about
cerebellar function could be made, trying to better define how the cerebellum is functionally
involved in the pathogenesis of isolated dystonia. Methodology can be divided into major
themes (i) two studies exploring cerebellar modulation of dystonic neurophysiological
hallmarks; impaired motor surround inhibition (chapter 2) and excessive plasticity (chapter 3)
(ii) evaluation of eye-blink conditioning a form of cerebellar associative learning (chapter 4,
chapter 8) (iii) exploring whether millisecond timing, a cerebellar encoded process, is at the
root of abnormal temporal discrimination thresholds (chapter 5) and finally (iv) testing
adaptation a kinematic cerebellar paradigm in cervical dystonia (chapter 6) and DYT1
dystonia (chapter 7).
Overall, my application of the ‘purest’ cerebellar paradigms did not provide a robust
functional correlate to implicate specific cerebellar functions as a driver of dystonic
pathophysiology. I present good evidence that fundamental computations such as adaptation
and associative learning are intact in various groups of isolated dystonia. Thus isolated
dystonia does not seem to selectively impair cerebellar functions (as currently defined). It is
only with future research that we will be able to determine whether dystonia corrupts
function(s) inherent to the dystonic network which includes the cerebellum or whether the
cerebellar abnormalities observed experimentally are compensatory in nature