Cortico-muscular coherence as an index of fatigue in multiple sclerosis

Background: Highly common in multiple sclerosis (MS), fatigue severely impacts patients' daily lives. Previous findings of altered connectivity patterns led to the hypothesis that the distortion of functional connections within the brain-muscle circuit plays a crucial pathogenic role. Objective: The objective of this paper is to identify markers sensitive to fatigue in multiple sclerosis. Methods: Structural (magnetic resonance imaging with assessment of thalamic volume and cortical thickness of the primary sensorimotor areas) and functional (cortico-muscular coherence (CMC) from simultaneous electroencephalo- and surface electromyographic recordings during a weak handgrip task) measures were used on 20 mildly disabled MS patients (relapsing-remitting course, Expanded Disability Status Scale score = 2) who were recruited in two fatigue-dependent groups according to the Modified Fatigue Index Scale (MFIS) score. Results: The two groups were similar in terms of demographic, clinical and imaging features, as well as task execution accuracy and weariness. In the absence of any fatigue-dependent brain and muscular oscillatory activity alterations, CMC worked at higher frequencies as fatigue increased, explaining 67% of MFIS variance (p=.002). Conclusion: Brain-muscle functional connectivity emerged as a sensitive marker of phenomena related to the origin of MS fatigue, impacting central-peripheral communication well before the appearance of any impairment in the communicating nodes.