First Application of a Novel Brain Template: Motor Training Improves Cortico-cerebellar Connectivity in Cerebellar Ataxia

People with cerebellar degeneration show characteristic ataxic motor impairments. Despite cerebellar dysfunction, they can improve motor performance through sensorimotor training. Yet, how such training changes functional brain networks affected by cerebellar degeneration is unknown. We here investigated neuroplastic changes in the cortico-cerebellar network after a 5-d forearm training in 40 patients with mild to severe cerebellar degeneration and 40 age- and sex-matched healthy controls. Human participants (41 female) were assigned to one of four motor training conditions, varying online visual feedback and explicit verbal feedback. Anatomical and resting-state fMRI was collected on days before and after training. To overcome the limitations of standard brain templates that fail when encountering severe anatomical abnormalities, we developed a specific template for comparing cerebellar patients with controls. Our new template reduced the spatial spread of cerebellar anatomical landmarks by 30% and tripled fMRI noise classification accuracy. Using this pipeline, we found that patients showed impaired connectivity between cerebellar motor regions and neocortical visuomotor and premotor regions at baseline compared with controls, whereas their corticocortical connectivity remained intact. Training with vision strengthened connectivity in the cortico-cerebellar visuomotor network contralateral to the trained arm in all participants. Cerebellar patients exhibited additional increased connectivity ipsilateral to the training arm in this network. Further, training with explicit verbal feedback affected connectivity between a cerebellar cognitive region and dorsolateral prefrontal cortex, although post hoc tests did not reach significance. These results document enhanced cortico-cerebellar connectivity as a neurophysiological response to visuomotor training in people with cerebellar degeneration.