Absence of BOLD adaptation in chronic fatigue syndrome revealed by task functional MRI.
Schönberg, Laura, Mohamed, Abdalla Z, Yu, Qiang et al. · Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2025 · DOI
Quick Summary
This study looked at how the brain responds when people with ME/CFS do mental tasks, using brain imaging to measure blood flow. Researchers found that while healthy people's brains become more efficient with repeated effort (showing less activation over time), people with ME/CFS showed the opposite pattern—their brains actually increased activity with each repetition. This suggests that ME/CFS may involve a fundamental difference in how the brain adapts to mental work, potentially explaining why cognitive tasks feel so exhausting.
Why It Matters
This is one of the first studies to examine how the ME/CFS brain fails to adapt efficiently during cognitive tasks, providing potential neurobiological evidence for why cognitive exertion worsens fatigue. The findings may help validate ME/CFS as a neurophysiological condition and guide future investigations into energy metabolism and neural efficiency in the disease.
Observed Findings
ME/CFS participants showed increased right postcentral gyrus activation during the second cognitive task block, whereas healthy controls showed decreased activation
Bilateral dynamic changes in motor, sensory, and cognitive cortices were significantly greater in ME/CFS compared to healthy controls
Bilateral changes in the left primary motor cortex correlated with patient-reported fatigue severity
ME/CFS participants demonstrated absence of normal BOLD adaptation across task repetition, suggesting impaired neural efficiency
Healthy controls exhibited the expected pattern of reduced brain activation with repeated cognitive effort
Inferred Conclusions
BOLD adaptation—a normal brain mechanism that improves energy efficiency—is absent in ME/CFS, suggesting a fundamental neurophysiological difference in cognitive processing
The paradoxical increase in brain activation with repeated cognitive effort in ME/CFS may underlie the pathological fatigue response characteristic of the disease
Abnormal neural adaptation patterns correlate with symptom severity, supporting a neurobiological basis for ME/CFS cognitive dysfunction
Remaining Questions
Does the absence of BOLD adaptation occur in other task types, or is this specific to this particular cognitive test?
What This Study Does Not Prove
This study does not prove that abnormal BOLD adaptation causes ME/CFS symptoms or that it is specific to ME/CFS—other conditions could show similar patterns. The correlation between motor cortex changes and fatigue severity suggests an association, but does not establish that one causes the other. Results may not generalize to ME/CFS patients with different disease severity levels or comorbidities.
Tags
Symptom:Cognitive DysfunctionFatigue
Biomarker:Neuroimaging
Method Flag:PEM Not DefinedSmall SampleExploratory Only
Can abnormal BOLD adaptation patterns predict disease severity or treatment response in ME/CFS patients?
What underlying cellular or metabolic mechanisms cause the failure of neural adaptation in ME/CFS—mitochondrial dysfunction, neurotransmitter abnormalities, or other factors?
Do patterns of BOLD adaptation change over time or in response to treatment interventions?