Cerebellar degeneration affects cortico-cortical connectivity in motor learning networks

Abstract

The cerebellum plays an important role in motor learning as part of a cortico-striato-cerebellar network. Patients with cerebellar degeneration typically show impairments in different aspects of motor learning, including implicit motor sequence learning. How cerebellar dysfunction affects interactions in this cortico-striato-cerebellar network is poorly understood. The present study investigated the effect of cerebellar degeneration on activity in causal interactions between cortical and subcortical regions involved in motor learning. We found that cerebellar patients showed learning-related increase in activity in two regions known to be involved in learning and memory, namely parahippocampal cortex and cerebellar Crus I. The cerebellar activity increase was observed in non-learners of the patient group whereas learners showed an activity decrease. Dynamic causal modeling analysis revealed that modulation of M1 to cerebellum and putamen to cerebellum connections were significantly more negative for sequence compared to random blocks in controls, replicating our previous results, and did not differ in patients. In addition, a separate analysis revealed a similar effect in connections from SMA and PMC to M1 bilaterally. Again, neural network changes were associated with learning performance in patients. Specifically, learners showed a negative modulation from right SMA to right M1 that was similar to controls, whereas this effect was close to zero in non-learners. These results highlight the role of cerebellum in motor learning and demonstrate the functional role cerebellum plays as part of the cortico-striato-cerebellar network.