Cerebellar Contributions to Motor and Cognitive Control in Multiple Sclerosis^✰✰✰

Objective: To evaluate relationships between specific cerebellar regions and common clinical measures of motor and cognitive function in persons with multiple sclerosis (PwMS). Design: Cross-sectional. Setting: Laboratory. Participants: Twenty-nine PwMS and 28 age- and sex-matched controls without multiple sclerosis (MS) (N=57). Interventions: Not applicable. Main Outcome Measures: Both diffusion and lobule magnetic resonance imaging analyses and common clinical measures of motor and cognitive function were used to examine structure-function relationships in the cerebellum. Results: PwMS demonstrate significantly worse motor and cognitive function than controls, including weaker strength, slower walking, and poorer performance on the Symbol Digit Modalities Test, but demonstrate no differences in cerebellar volume. However, PwMS demonstrate significantly worse diffusivity (mean diffusivity: P=.0003; axial diffusivity: P=.0015; radial diffusivity: P=.0005; fractional anisotropy: P=.016) of the superior cerebellar peduncle, the primary output of the cerebellum. Increased volume of the motor lobules (I-V, VIII) was significantly related to better motor (P<.022) and cognitive (P=.046) performance, and increased volume of the cognitive lobules (VI-VII) was also related to better motor (P<.032) and cognitive (P=.008) performance, supporting the role of the cerebellum in both motor and cognitive functioning. Conclusions: These data highlight the contributions of the cerebellum to both motor and cognitive function in PwMS. Using novel neuroimaging techniques to examine structure-function relationships in PwMS improves our understanding of individualized differences in this heterogeneous group and may provide an avenue for targeted, individualized rehabilitation aimed at improving cerebellar dysfunction in MS.