Aim of this study was to explore the topological organization of functional brain network connectivity in a large cohort of multiple sclerosis (MS) patients and to assess whether its disruption contributes to disease clinical manifestations. Graph theoretical analysis was applied to resting state fMRI data from 246 MS patients and 55 matched healthy controls (HC). Functional connectivity between 116 cortical and subcortical brain regions was estimated using a bivariate correlation analysis. Global network properties (network degree, global efficiency, hierarchy, path length and assortativity) were abnormal in MS patients vs HC, and contributed to distinguish cognitively impaired MS patients (34 %) from HC, but not the main MS clinical phenotypes. Compared to HC, MS patients also showed: (1) a loss of hubs in the superior frontal gyrus, precuneus and anterior cingulum in the left hemisphere; (2) a different lateralization of basal ganglia hubs (mostly located in the left hemisphere in HC, and in the right hemisphere in MS patients); and (3) a formation of hubs, not seen in HC, in the left temporal pole and cerebellum. MS patients also experienced a decreased nodal degree in the bilateral caudate nucleus and right cerebellum. Such a modification of regional network properties contributed to cognitive impairment and phenotypic variability of MS. An impairment of global integration (likely to reflect a reduced competence in information exchange between distant brain areas) occurs in MS and is associated with cognitive deficits. A regional redistribution of network properties contributes to cognitive status and phenotypic variability of these patients.
