CEREBELLAR CONTROL OF CORTICO STRIATAL PLASTICITY & THERAPEUTIC CEREBELLAR DEEP BRAIN STIMULATIONS IN DYSTONIA

Dystonia is a neurological syndrome characterized by involuntary, abnormal movements and postures, resulting from the simultaneous activation of opposing muscles. This disorder is associated with aberrant cortico-striatal synaptic plasticity, characterized by impaired synaptic scaling down. Our previous work revealed downstream alterations within the cerebello–thalamo–cortical pathway. In this context, we showed that cerebellar θ-burst stimulation can restore these communication deficits in a genetic model of dystonia (DYT25), resulting in a significant, though modest, improvement in motor symptoms.
Here, we further investigate behavioral symptoms and neurophysiological changes in cerebello–cortico–striatal communication during dystonic crises in the same model. Our aim is to characterize plasticity changes associated with dystonia and to propose stimulation protocols to better improve motor activity.
Preliminary results reveal aberrant oscillatory activity in the motor cortex within the theta frequency range, associated with the symptomatic state in DYT25 mice. Building on this observation, a closed-loop stimulation approach was implemented, triggered by the oscillatory phase within the identified pathological frequency range. Three stimulation paradigms were tested: open-loop stimulation, or stimulation locked to either the ascending or descending phase of the oscillation. Strikingly, these approaches produced opposite effects on both pathway functional connectivity and motor symptoms. Together, these findings suggest that the effects of cerebellar stimulation may depend on the cortical oscillatory state, highlighting the potential importance of state-dependent network dynamics in dystonia.