Multiple sclerosis impairs regional functional connectivity in the cerebellum

Resting-state functional magnetic resonance imaging (rs-fMRI) has been used to study changes in long-range functional brain connectivity in multiple sclerosis (MS). Yet little is known about how MS affects functional brain connectivity at the local level. Here we studied 42 patients with MS and 30 matched healthy controls with whole-brain rs-fMRI at 3 T to examine local functional connectivity. Using the Kendall's Coefficient of Concordance, regional homogeneity of blood-oxygen-level-dependent (BOLD)-signal fluctuations was calculated for each voxel and used as a measure of local connectivity. Patients with MS showed a decrease in regional homogeneity in the upper left cerebellar hemisphere in lobules V and VI relative to healthy controls. Similar trend changes in regional homogeneity were present in the right cerebellar hemisphere. The results indicate a disintegration of regional processing in the cerebellum in MS. This might be caused by a functional disruption of cortico-ponto-cerebellar and spino-cerebellar inputs, since patients with higher lesion load in the left cerebellar peduncles showed a stronger reduction in cerebellar homogeneity. In patients, two clusters in the left posterior cerebellum expressed a reduction in regional homogeneity with increasing global disability as reflected by the Expanded Disability Status Scale (EDSS) score or higher ataxia scores. The two clusters were mainly located in Crus I and extended into Crus II and the dentate nucleus but with little spatial overlap. These findings suggest a link between impaired regional integration in the cerebellum and general disability and ataxia.