Cerebellum and cognition in progressive MS patients: functional changes beyond atrophy?

Background: The cerebellum is a predilection site of pathology in progressive multiple sclerosis (PMS) patients, contributing to cognitive deficits. Aim of this study was to investigate lobular cerebellar functional connectivity (FC) in PMS patients in relation to cognition. Methods: In this cross-sectional study, resting state fMRI analysis was carried out on 29 PMS patients (11 males, mean age 51.2 ± 11.9 years) and 22 age- and sex-matched healthy controls (HC) (11 males, mean age 49.6 ± 8.8 years). Data were analyzed with a seed-based approach, with four different seeds placed at the level of cerebellar Lobule VI, Crus I, Crus II and Lobule VIIb, accounting for cerebellar structural damage. Cognitive status was assessed with the BICAMS battery. Correlations between fMRI data and clinical variables were probed with the Spearman correlation coefficient. Results: When testing FC differences between PMS and HC without taking into account cerebellar structural damage, PMS patients showed a reduction of FC between Crus II/Lobule VIIb and the right frontal pole (p = 0.001 and p = 0.002, respectively), with an increased FC between Lobule VIIb and the right precentral gyrus (p < 0.001). After controlling for structural damage, PMS patients still showed a reduced FC between Crus II and right frontal pole (p = 0.005), as well as an increased FC between Lobule VIIb and right precentral gyrus (p = 0.003), with the latter showing an inverse correlation with BVMT scores (r = − 0.393; p = 0.03). Conclusion: PMS patients show cerebellar FC rearrangements that are partially independent from cerebellar structural damage, and are likely expression of a maladaptive functional rewiring.