Associations of White Matter and Basal Ganglia Microstructure to Cognitive Fatigue Rate in Multiple Sclerosis

Fatigue, including cognitive fatigue, is one of the most debilitating symptoms reported by persons with multiple sclerosis (pwMS). Cognitive fatigue has been associated with disruptions in striato-thalamo-cortical and frontal networks, but what remains unknown is how the rate at which pwMS become fatigued over time relates to microstructural properties within the brain. The current study aims to fill this gap in knowledge by investigating how cognitive fatigue rate relates to white matter and basal ganglia microstructure in a sample of 62 persons with relapsing-remitting MS. Participants rated their level of cognitive fatigue at baseline and after each block (x7) of a within-scanner cognitive fatigue inducing task. The slope of the regression line of all eight fatigue ratings was designated as "cognitive fatigue rate." Diffusional kurtosis imaging maps were processed using tract-based spatial statistics and regional analyses (i.e., basal ganglia) and associated with cognitive fatigue rate. Results showed cognitive fatigue rate to be related to several white matter tracts, with many having been associated with basal ganglia connectivity or the previously proposed "fatigue network." In addition, cognitive fatigue rate was associated with the microstructure within the putamen, though this did not survive multiple comparisons correction. Our approach of using cognitive fatigue rate, rather than trait fatigue, brings us closer to understanding how brain pathology may be impacting the experience of fatigue in the moment, which is crucial for developing interventions. These results hold promise for continuing to unpack the complex construct that is cognitive fatigue.