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

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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.

Original languageEnglish
Pages (from-to)1352458521999274
JournalMultiple Sclerosis
Publication statusE-pub ahead of print - 8 Mar 2021

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