Fatigue in Multiple Sclerosis: a resting-state EEG microstate study

Fatigue affects approximately 80% of people with Multiple Sclerosis (PwMS) and can impact several domains of daily life. However, the neural underpinnings of fatigue in MS are still not completely clear. The aim of our study was to investigate the spontaneous large-scale networks functioning associated with fatigue in PwMS using the EEG microstate approach with a spectral decomposition. Forty-three relapsing-remitting MS patients and twenty-four healthy controls (HCs) were recruited. All participants underwent an administration of Modified Fatigue Impact scale (MFIS) and a 15-min resting-state high-density EEG recording. We compared the microstates of healthy subjects, fatigued (F-MS) and non-fatigued (nF-MS) patients with MS; correlations with clinical and behavioral fatigue scores were also analyzed. Microstates analysis showed six templates across groups and frequencies. We found that in the F-MS emerged a significant decrease of microstate F, associated to the salience network, in the broadband and in the beta band. Moreover, the microstate B, associated to the visual network, showed a significant increase in fatigued patients than healthy subjects in broadband and beta bands. The multiple linear regression showed that the high cognitive fatigue was predicted by both an increase and decrease, respectively, in delta band microstate B and beta band microstate F. On the other hand, higher physical fatigue was predicted with lower occurrence microstate F in beta band. The current findings suggest that in MS the higher level of fatigue might be related to a maladaptive functioning of the salience and visual network.