Divergent Cerebello-Cortical Network Responses to Emotional Stress in Myoclonus Dystonia

In myoclonus dystonia (DYT-SGCE) psychiatric features such as anxiety and depression are frequent comorbidities. The neural mechanisms underlying these negative emotional states in DYT-SGCE remain poorly understood. Task-based functional magnetic resonance imaging (fMRI), by measuring task-evoked functional connectivity during emotion processing, offers mechanistic insight into the pathophysiology of nonmotor features in DYT-SGCE.

The aim was to investigate effective connectivity alterations in the neural network associated with the experience of negative emotions in DYT-SGCE. We hypothesized that patients show impaired regulation of negative emotions due to altered connectivity between the nonmotor cerebellum and its associated cortical regions.

DYT-SGCE patients and healthy volunteers (HV) performed an fMRI task involving conscious recall of personal emotional experiences under stressful and neutral-relaxing conditions. An emotional network was identified using data-driven activation maps, and generalized psychophysiological interactions were applied to compare connectivity modulation between conditions across groups.

Twenty DYT-SGCE patients and 20 HVs were enrolled in the study. DYT-SGCE patients exhibited increased connectivity from the cerebellum to the precuneus, medial prefrontal, and middle temporal cortices during the stressful condition compared to the neutral-relaxing condition. Clinically, DYT-SGCE patients showed higher anxiety scores. Across groups, higher trait of anxiety was associated with further amplification of cerebello-cortical connectivity in these regions, but severity of anxiety was not directly correlated with connectivity in patients. No changes in connectivity or correlations with anxiety were observed for cortico-cerebellar, cerebello-cerebellar, or cortico-cortical connections.

These findings emphasize the role of the cerebellum in emotional regulation dysfunction in DYT-SGCE, which may underlie the patients' psychiatric phenotype. © 2026 International Parkinson and Movement Disorder Society.