Increased connectivity of hub networks and cognitive impairment in multiple sclerosis

Objective: To investigate default-mode network (DMN) and frontoparietal network (FPN) dysfunction in cognitively impaired (CI) patients with multiple sclerosis (MS) because these networks strongly relate to cognition and contain most of the hubs of the brain. Methods: Resting-state fMRI and neuropsychological assessments were performed in 322 patients with MS and 96 healthy controls (HCs). Patients with MS were classified as CI (z score ,22.0 on at least 2 tests; n 5 87), mildly cognitively impaired (z score,21.5 on at least 2 tests and not CI; n 5 65), and cognitively preserved (CP; n 5 180). Within-network connectivity, connectivity with the rest of the brain, and between-network connectivity were calculated and compared between groups. Connectivity values were normalized for individual means and SDs. Results: Only in CI, both the DMN and FPN showed increased connectivity with the rest of the brain compared to HCs and CP, with no change in within- or between-network connectivity. Regionally, this increased connectivity was driven by the inferior parietal, posterior cingulate, and angular gyri. Increased connectivity with the rest of the brain correlated with worse cognitive performance, namely attention for the FPN as well as information processing speed and working memory for both networks. Conclusions: In CI patients with MS, the DMN and FPN showed increased connectivity with the rest of the brain, while normal within- and between-network connectivity levels were maintained. These findings indicate that cognitive impairment in MS features disturbed communication of hub-rich networks, but only with the more peripheral (i.e., nonhub) regions of the brain.