Brain Activity and Connectivity in Fatigued People with Multiple Sclerosis During a Static Balance Task: An fNIRS Study

Fatigue and balance disorders are common in people with multiple sclerosis (PwMS), but the neural mechanisms linking them during postural control remain unclear. This cross-sectional study aims to examine associations between fatigue, balance impairment, and task-evoked cortical hemodynamics/connectivity. Sixteen PwMS (relapsing-remitting MS; EDSS < 3.5) and 19 healthy controls (HC) were enrolled. Based on the Modified Fatigue Impact Scale (MFIS), PwMS were classified as fatigued (f_PwMS, MFIS ≥ 38; n = 10) or non-fatigued (nf_PwMS, n = 6). Participants performed five 30 s trials of static stance on foam with eyes closed. fNIRS recorded frontal, temporal, and occipital cortical activity, while stabilometry measured center-of-pressure sway. In PwMS, MFIS showed a trend toward association with sway (r = 0.49; p = 0.06). Sway was higher in f_PwMS than nf_PwMS and HC but not significantly different (ANOVA p = 0.341). Compared with HC, PwMS showed increased bilateral prefrontal and reduced occipital HR. Stratified analyses showed greater HR in f_PwMS versus HC and nf_PwMS in bilateral BA10 and in temporo-parietal regions, with a right-hemisphere predominance. Global coherence did not differ across groups, but exploratory BA10 analysis showed higher prefrontal coherence in f_PwMS than nf_PwMS (p = 0.02). Fatigued PwMS exhibit amplified, right prefrontal and temporo-parietal activation and focal prefrontal hyper-connectivity, consistent with compensatory top–down control to maintain balance.