Pathophysiology of dystonia: Models and mechanisms

Dystonia has generally been considered a basal ganglia disorder. Increasing evidence, however, suggests a more system-wide disruption of brain circuitry involving cerebellar and brainstem pathophysiology reflected in altered firing patterns, synchronized oscillations, as well as widened receptive fields and abnormal plasticity. A model of dystonia incorporating observed pathophysiological properties within the basal ganglia thalamocortical and cerebellothalamocortical circuits (BGTC and CTC) is presented. In this model, we postulate that disruption in the BGTC arises from functional changes within the striatum, while alterations in the CTC arise independently but contribute to the development and expression of dystonia. The degree to which changes in firing rates/patterns and broadened receptive fields in these circuits contribute to the manifestation of dystonia is unclear but may be secondary to the development of uncontrolled temporal-spatial changes in synchronization and underlying changes in neuro-plasticity within these circuits. The continued review and modification of established theories and development of emerging pathophysiological models of dystonia is critical to improving our approach to treatment; this is particularly true for refining surgical therapies such as therapeutic deep-brain stimulation (DBS).