Progressive brain rich-club network disruption from clinically isolated syndrome towards multiple sclerosis

Objective To investigate the rich-club organization in clinically isolated syndrome (CIS) and multiple sclerosis (MS), and to characterize its relationships with physical disabilities and cognitive impairments. Methods We constructed high-resolution white matter (WM) structural networks in 41 CIS, 32 MS and 35 healthy controls (HCs) using diffusion MRI and deterministic tractography. Group differences in rich-club organization, global and local network metrics were investigated. The relationship between the altered network metrics, brain lesions and clinical variables including EDSS, MMSE, PASAT, disease duration were calculated. Additionally, reproducibility analysis was performed using different parcellation schemes. Results Compared with HCs, MS patients exhibited a decreased strength in all types of connections (rich-club: p
Highlights • The rich-club organization was disrupted in MS patients and preserved in CIS. • The disrupted rich-club connectivity correlated with cognitive impairment in MS. • The rich-club results are reproducible across data analysis methods.