The cerebellum and its network: Disrupted static and dynamic functional connectivity patterns and cognitive impairment in multiple sclerosis.

BACKGROUND The impact of cerebellar damage and (dys)function on cognition remains understudied in multiple sclerosis. OBJECTIVE To assess the cognitive relevance of cerebellar structural damage and functional connectivity (FC) in relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS). METHODS This study included 149 patients with early RRMS, 81 late RRMS, 48 SPMS and 82 controls. Cerebellar cortical imaging included fractional anisotropy, grey matter volume and resting-state functional magnetic resonance imaging (MRI). Cerebellar FC was assessed with literature-based resting-state networks, using static connectivity (that is, conventional correlations), and dynamic connectivity (that is, fluctuations in FC strength). Measures were compared between groups and related to disability and cognition. RESULTS Cognitive impairment (CI) and cerebellar damage were worst in SPMS. Only SPMS showed cerebellar connectivity changes, compared to early RRMS and controls. Lower static FC was seen in fronto-parietal and default-mode networks. Higher dynamic FC was seen in dorsal and ventral attention, default-mode and deep grey matter networks. Cerebellar atrophy and higher dynamic FC together explained 32% of disability and 24% of cognitive variance. Higher dynamic FC was related to working and verbal memory and to information processing speed. CONCLUSION Cerebellar damage and cerebellar connectivity changes were most prominent in SPMS and related to worse CI.