The biology behind mental fatigue: Is your brain tired? Researchers are discovering the roots of mental fatigue. Better ways to measure cognitive exhaustion could point to treatments for long COVID and other debilitating disorders.
Cognitive fatigue is being studied more intensively due to its prevalence in conditions such as long COVID, chronic fatigue syndrome, and multiple sclerosis, with researchers developing better biomarkers, behavioral tools and potential treatments. Leading theories suggest that when the brain engages in sustained, effortful thinking such as complex problem-solving or navigating unfamiliar situations, demands on neural circuits may deplete cellular energy or allow metabolic waste products like glutamate to accumulate, triggering fatigue as a protective signal to rest.