Fatigue Is Associated With Altered Monitoring and Preparation of Physical Effort in Patients With Chronic Fatigue Syndrome

Chronic fatigue syndrome (CFS) is characterized by disabling fatigue, which is suggested to be maintained by dysfunctional beliefs. Fatigue and its maintenance are recently conceptualized as arising from abnormally precise expectations about bodily inputs and from beliefs of diminished control over bodily states, respectively. This study used functional neuroimaging to identify the neural correlates of fatigue and its maintenance by beliefs during a physical effort task. We isolated behavioral adjustments and cerebral activity during feedback processing and motor preparation, in the context of a task in which patients with CFS (n = 85) and healthy control subjects (n = 29) produced 30%, 50%, and 70% of their right-hand maximal voluntary contraction, and received directional feedback on performance (e.g., too little force). Patients with CSF showed an effort-dependent behavioral bias toward less effort investment in response to directional feedback for the highest effort level as compared with healthy control subjects. This bias was associated with reduced feedback-related activity in the dorsolateral prefrontal cortex. These effects were proportional to state-related fatigue and prior beliefs about CFS patients’ ability to perform the task. Patients with CFS also showed higher activity in the supplementary motor area, proportional to their state-related fatigue, and reduced connectivity between the supplementary motor area and sensorimotor cortex during motor preparation as compared with control subjects. These findings link fatigue symptoms to alterations in behavioral choices on effort investment, prefrontal functioning, and supplementary motor area connectivity, with the dorsolateral prefrontal cortex being associated with prior beliefs about physical abilities.