Cerebellar Atrophy in Multiple System Atrophy (Cerebellar Type) and Its Implication for Network Connectivity

We sought to assess structural and functional patterns of cerebellum in multiple system atrophy (cerebellar type), and investigate the associations of structural and functional cerebellar gray matter abnormalities. We collected magnetic resonance imaging data of 18 patients with multiple system atrophy (cerebellar type) and 18 health control subjects. The gray matter loss across the motor and cognitive cerebellar territories in patients was assessed using voxel-based morphometry. And change in the connectivity between the cerebellum and large-scale cortical networks was assessed using resting-state functional MRI analysis. Furthermore, we assessed the relationship between the extent of cerebellar atrophy and reduced-activation in the cerebellar-cortical and subthalamo-cerebellar functional connectivities. We confirmed the gray matter loss across the motor and cognitive cerebellar territories in patients and found that the extent of cerebellar atrophy was correlated with decreased connectivity between the cerebellum and large-scale cortical networks, including the default, frontal parietal, and sensorimotor networks. The volume reduction in the motor cerebellum was closely associated with the clinical motor severity. A post hoc analysis showed reduced-activation in the subthalamo-cerebellar functional connectivity without the subthalamic nucleus atrophy. These results emphasized significant atrophy in the cerebellar subsystem and its association with the large-scale cortical networks in multiple system atrophy (cerebellar type), which may improve our understanding of the neural pathophysiology mechanisms of disease.