Schumann, Andy, Di Giuliano, Monica, Schulz, Steffen et al. · Brain communications · 2025 · DOI
Scientists analyzed brain imaging studies from 46 different research projects involving over 2,600 people to understand how fatigue affects the brain. They found that mental fatigue—the kind experienced in ME/CFS, long COVID, and other conditions—involves a network of interconnected brain regions, particularly in areas responsible for thinking, emotions, and body awareness. These brain regions don't communicate properly when people experience severe fatigue, which may explain why fatigue is so hard to overcome.
This study provides the first comprehensive transdiagnostic map of brain regions involved in mental fatigue, directly supporting ME/CFS research by showing that fatigue involves specific, measurable brain network dysfunction rather than being psychological. Understanding these brain networks is crucial for developing targeted treatments and validating ME/CFS as a neurobiological condition. The findings may help explain why standard treatments for other conditions often fail in ME/CFS patients and guide development of more effective interventions.
This meta-analysis identifies brain regions associated with fatigue but does not prove causation—abnormal activation could be a consequence of fatigue rather than its cause. The study does not test specific treatments or predict which patients will respond to particular therapies. Individual variation in brain activation patterns means these findings describe group-level trends and may not apply equally to all ME/CFS patients.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
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