Abnormal functional connectivity of white-matter networks and gray-white matter functional networks in patients with NMOSD

Cognitive impairment (CI) has been reported in 29 - 70% of patients with neuromyelitis optica spectrum disorder (NMOSD). Abnormal white matter (WM) functional networks that correlate with cognitive functions have not been studied well in patients with NMOSD. The aim of the current study was to investigate functional connectivity (FC), spontaneous activity, and functional covariance connectivity (FCC) abnormalities of WM functional networks in patients with NMOSD and their correlation with cognitive performance. Twenty-four patients with NMOSD and 24 healthy controls (HCs) were included in the study. Participants underwent brain resting-state functional magnetic resonance imaging (fMRI) and the Montreal Cognitive Assessment (MoCA). Eight WM networks and nine gray matter (GM) networks were created. In patients, WM networks, including WM1 - 4, WM1 - 8, WM2 - 6, WM2 - 7, WM2 - 8, WM4 - 8, WM5 - 8 showed reduced FC (P < 0.05). All WM networks except WM1 showed decreased spontaneous activity (P < 0.05). The major GM networks demonstrated increased/ decreased FC (P < 0.05), whereas GM7-WM7, GM8-WM4, GM8-WM6 and GM8-WM8 displayed decreased FC (P < 0.05). The MoCA results showed that two-thirds (16/24) of the patients had CI. FC and FCC in WM networks were correlated negatively with the MoCA scores (P < 0.05). WM functional networks are multi-layered. Abnormal FC of WM functional networks and GM functional networks may be responsible for CI.