Central origin of fatigability in Myalgic encephalomyelitis/chronic fatigue syndrome revealed by multimodal neuroimaging.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating chronic disease characterized by physical and mental fatigue, post-exertional malaise, muscle pain, headaches, and unrefreshing sleep. Fatigability refers to a reduction of muscular force over time despite willed effort and has a central and a peripheral component. We studied whether fatigability in ME/CFS is related to central or peripheral mechanisms. We recruited fifteen patients with ME/CFS and nineteen age- and sex-matched healthy volunteers (with seven females in each group). Participants performed a fatiguing grip force task, requiring them to maintain 50% of their maximum voluntary force during alternating 30 s blocks of grip and rest. We simultaneously recorded grip force, forearm muscle activity with electromyography, and brain activity with electroencephalography and functional magnetic resonance imaging. Fatigue onset was based on grip force performance and was set individually for each participant. ME/CFS patients generated the same level of maximum voluntary force than healthy volunteers but developed fatigue much earlier. Healthy volunteers increased their muscle and brain activity from the beginning of the task until the onset of fatigue. Specifically, muscle activity shifted from high to low frequencies and brain activity increased steadily in cortical and subcortical areas. Then, muscle and brain activity declined slowly. In contrast, in ME/CFS, the muscles and brain activity only showed minimal fluctuations across all the task blocks. The earlier onset of fatigue in ME/CFS is related to central mechanisms, as their brain did not increase its output to drive muscle activity like healthy volunteers did. While this is a small sample study, and caution should be taken regarding the generalizability of the results, the earlier onset of fatigue in ME/CFS was observed to be related to central mechanisms. The brain in ME/CFS participants did not increase its output to drive muscle activity like healthy volunteers did.