The specificity of fatigue cerebral substrates in early Multiple Sclerosis - An fMRI study

Guillemin, C.; Charonitis, M.; Beliy, N.; Requier, F.; Delrue, G.; Lommers, E.; Vandewalle, G.; Maquet, P.; Phillips, C.; Collette, F.

doi:10.1101/2025.06.27.661966

bioRxiv · 10.1101/2025.06.27.661966

The specificity of fatigue cerebral substrates in early Multiple Sclerosis - An fMRI study

Guillemin, C.·Charonitis, M.·Beliy, N.·Requier, F.·Delrue, G.·Lommers, E.·Vandewalle, G.·Maquet, P.·Phillips, C.·Collette, F.

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Abstract

ContextThe cerebral substrates of fatigue in patients with Multiple Sclerosis (pwMS) are not elucidated yet. This study aims at exploring the disease-specific functional brain substrates of fatigue in pwMS with a recent disease history MethodsSixteen pwMS (disease history < 5 years) and 17 matched Healthy Controls (HC) performed a N-Back task with three difficulty levels during fMRI acquisitions following high vs. low fatigue induction. Measures of subjective trait and state fatigue were also recorded. Behavioral performance at n-back task and evolution of subjective fatigue states were analyzed by means of Bayesian repeated measures analyses of variance. Functional MRI data were analyzed to determine between-group differences (1) in task-related brain activity, independently of trait fatigue score; (2) in the association between trait fatigue and brain activity ResultsA similar trajectory was observed in the two groups for subjective and task-related measures following fatigue induction. No between-group difference was observed in brain activity unrelated to fatigue score. However, negative associations between trait fatigue score and brain activity were observed in pwMS, while the associations are positive in HC. Specifically, interactions between group and task difficulty were observed in regions belonging to the Striato-Thalamo-Cortical (STC) network and the fronto-parietal cortex ConclusionGroup-specific patterns of brain activity related to fatigue were identified in pwMS and HC in the STC circuitry, despite similar behavioral performance and subjective fatigue level. This confirms the implication of the STC loops in fatigue pathophysiology, occurring from the early stages of the disease.

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Guillemin, C., Charonitis, M., Beliy, N., Requier, F., Delrue, G., Lommers, E., Vandewalle, G., Maquet, P., Phillips, C., Collette, F.. 2025-06-28. The specificity of fatigue cerebral substrates in early Multiple Sclerosis - An fMRI study. https://doi.org/10.1101/2025.06.27.661966

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