White matter tract network disruption explains reduced conscientiousness in multiple sclerosis.

Quantifying white matter (WM) tract disruption in people with multiple sclerosis (PwMS) provides a novel means for investigating the relationship between defective network connectivity and clinical markers. PwMS exhibit perturbations in personality, where decreased Conscientiousness is particularly prominent. This trait deficit influences disease trajectory and functional outcomes such as work capacity. We aimed to identify patterns of WM tract disruption related to decreased Conscientiousness in PwMS. Personality assessment and brain MRI were obtained in 133 PwMS and 49 age- and sex-matched healthy controls (HC). Lesion maps were applied to determine the severity of WM tract disruption between pairs of gray matter regions. Next, the Network-Based-Statistics tool was applied to identify structural networks whose disruption negatively correlates with Conscientiousness. Finally, to determine whether these networks explain unique variance above conventional MRI measures and cognition, regression models were applied controlling for age, sex, brain volume, T2-lesion volume, and cognition. Relative to HCs, PwMS exhibited lower Conscientiousness and slowed cognitive processing speed (p = .025, p = .006). Lower Conscientiousness in PwMS was significantly associated with WM tract disruption between frontal, frontal-parietal, and frontal-cingulate pathways in the left (p = .02) and right (p = .01) hemisphere. The mean disruption of these pathways explained unique additive variance in Conscientiousness, after accounting for conventional MRI markers of pathology and cognition (ΔR  = .049, p = .029). Damage to WM tracts between frontal, frontal-parietal, and frontal-cingulate cortical regions is significantly correlated with reduced Conscientiousness in PwMS. Tract disruption within these networks explains decreased Conscientiousness observed in PwMS as compared with HCs.