The constrained brain in multiple sclerosis: Cognitive impairment is related to network-specific coupling of structural and functional connectivity

Background: Cognitive impairment in multiple sclerosis (MS) is related to abnormal structural and functional brain network changes. As both modalities have mostly been studied separately, structure connectivity-function coupling (SC-FC) may elucidate how function is constrained by structure. Objectives: We examine how changes in SC-FC and its dynamics SC-FC (dSC-FC) may underlie MS-related cognitive impairment. Methods: We classified 266 people with MS (PwMS) as cognitively impaired (CI; z < −2 on ≥2/7 cognitive abilities compared to healthy controls [HC]) or preserved (CP; z > −1.5 on ≥2/7 abilities). Derived from diffusion-weighted and functional magnetic resonance imaging, SC-FC reflected the correlation coefficient between structural and functional connectivity, while dSC-FC reflected its variability. Whole-brain, within-network, and between-network (d)SC-FC were compared between 95 HC, 197 CP, and 69 CI. Results: Compared to CP and HC, CI showed higher SC-FC for connections extending from the dorsal attention (DAN; p ≤ 0.006) and somatomotor networks (p ≤ 0.024), and higher dSC-FC within the visual network (p ≤ 0.003) and deep grey matter (p ≤ 0.006). SC-FC in connections extending from the DAN predicted CP/CI status in PwMS (β = 0.069, OR = 1.072 [95% CI = 1.009–1.139], p = 0.025). Conclusions: In MS-related CI, deterioration of structural pathways is paired with loss of functional strength in connections extending from the DAN. This may hinder DAN-mediated stimulus selection, possibly contributing to CI.