E2 ModeratePreliminaryPEM requiredCross-SectionalPeer-reviewedReviewed
Alteration of Cortical Volume and Thickness in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.
Thapaliya, Kiran, Marshall-Gradisnik, Sonya, Staines, Donald et al. · Frontiers in neuroscience · 2022 · DOI
Quick Summary
Researchers used brain imaging to compare the brains of people with ME/CFS to healthy people. They found that people with ME/CFS had some areas of the brain that were thinner and other areas that were larger, particularly in regions involved in thinking and emotion. These brain differences were also connected to how severe symptoms like fatigue, sleep problems, and cognitive difficulties were in each person.
Why It Matters
This study provides neurobiological evidence that ME/CFS involves measurable structural brain changes, supporting the recognition of ME/CFS as a neurological condition rather than purely psychological. Understanding these brain differences may help validate patient experiences and guide future research into disease mechanisms and potential biomarkers.
Observed Findings
- Reduced cortical thickness in the caudal middle frontal gyrus (p=0.0016) and precuneus (p=0.013) in ME/CFS patients compared to healthy controls.
- Significantly increased amygdala volume in ME/CFS patients compared to healthy controls (p=0.002).
- Abnormal relationships between cortical volume/thickness and fatigue severity in ME/CFS patients versus healthy controls.
- Abnormal correlations between brain measures and heart rate variability, sleep disturbance scores, and cognitive performance in ME/CFS patients.
Inferred Conclusions
- Cortical structural alterations are present in ME/CFS and may contribute to neurocognitive impairment experienced by patients.
- The abnormal relationship between symptom severity and brain structure suggests different neurobiological processes in ME/CFS compared to healthy individuals.
- Multiple brain regions are affected in ME/CFS, suggesting widespread rather than focal neurological involvement.
Remaining Questions
- Are these brain structural changes present before illness onset, or do they develop as a consequence of ME/CFS?
- Do these structural changes correlate with or predict treatment response or symptom improvement?
- How do these findings relate to functional brain abnormalities and inflammatory markers in ME/CFS?
What This Study Does Not Prove
This study does not prove that the observed brain changes cause ME/CFS symptoms or that they are unique to ME/CFS; similar changes could occur in other conditions. The cross-sectional design cannot establish whether these brain alterations precede symptom onset, develop because of the illness, or result from its consequences. The small sample size limits the generalizability of findings to all ME/CFS patients.
Tags
Symptom:Cognitive DysfunctionUnrefreshing SleepFatigue
Biomarker:Neuroimaging
Method Flag:Small SampleExploratory Only
Metadata
- DOI
- 10.3389/fnins.2022.848730
- PMID
- 35527811
- Review status
- Editor reviewed
- Evidence level
- Single-study or moderate support from human research
- 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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