E3 PreliminaryModerate confidencePEM not requiredMechanisticPeer-reviewedReviewed
Fatigue Is Associated With Altered Monitoring and Preparation of Physical Effort in Patients With Chronic Fatigue Syndrome.
van der Schaaf, Marieke E, Roelofs, Karin, de Lange, Floris P et al. · Biological psychiatry. Cognitive neuroscience and neuroimaging · 2018 · DOI
Quick Summary
This study used brain imaging to understand why people with ME/CFS feel so fatigued and struggle with physical effort. Researchers asked patients and healthy people to squeeze a hand device at different force levels and give them feedback on their performance. People with ME/CFS were more likely to use less effort after feedback, especially at higher effort levels, and this related to lower activity in a brain region involved in decision-making and planning.
Why It Matters
This study provides neurobiological evidence that ME/CFS fatigue involves measurable changes in brain function during effort decisions and motor preparation, not just psychological factors. Understanding these mechanisms could inform more targeted interventions and validate the physiological basis of symptom severity, potentially improving how clinicians and researchers conceptualize the condition.
Observed Findings
- CFS patients showed greater behavioral bias toward reduced effort investment at the highest effort level (70% MVC) following directional feedback compared to controls.
- Reduced dorsolateral prefrontal cortex activity during feedback processing in CFS patients, proportional to state fatigue and prior beliefs about task performance.
- Elevated supplementary motor area activity in CFS patients during motor preparation, proportional to state fatigue.
- Reduced functional connectivity between supplementary motor area and sensorimotor cortex during motor preparation in CFS versus controls.
Inferred Conclusions
- Fatigue in ME/CFS is associated with dysfunctional effort allocation decisions, possibly driven by altered cost–benefit evaluation in prefrontal circuits.
- Prior beliefs about physical ability and bodily control influence both neural responses and behavioral effort choices in CFS patients.
- Motor preparation abnormalities suggest altered integration between higher planning regions and motor execution systems during physical effort.
Remaining Questions
- Do these neural alterations predate symptom onset, or do they develop as a consequence of illness? Can changes in brain activity predict treatment response or functional recovery?
- How do these neural patterns relate to post-exertional malaise and symptom exacerbation outside the laboratory setting?
What This Study Does Not Prove
This study does not establish causation—it shows that altered brain activity is associated with fatigue, but does not prove whether these brain changes cause fatigue or result from it. The findings are correlational and based on a single effort task; they may not generalize to other types of exertion or daily life. The study also does not address whether these neural differences are primary pathology or secondary to deconditioning or other factors.
Tags
Symptom:FatigueCognitive Dysfunction
Biomarker:Neuroimaging
Method Flag:PEM Not DefinedWeak Case DefinitionExploratory OnlySmall Sample
Metadata
- DOI
- 10.1016/j.bpsc.2018.01.015
- PMID
- 29628071
- Review status
- Editor reviewed
- Evidence level
- Early hypothesis, preprint, editorial, or weak support
- Last updated
- 12 April 2026
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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