Neuroimaging characteristics of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a systematic review.
Shan, Zack Y, Barnden, Leighton R, Kwiatek, Richard A et al. · Journal of translational medicine · 2020 · DOI
Quick Summary
This study reviewed 63 brain imaging research papers published over 30 years to identify what brain abnormalities are consistently found in ME/CFS patients. Researchers found that ME/CFS is commonly associated with unusual patterns of brain activity during thinking tasks and problems in the brain stem (the part controlling basic body functions). The findings suggest that the brains of people with ME/CFS may not be delivering oxygen and nutrients to active brain areas as efficiently as they should.
Why It Matters
This comprehensive review provides the first systematic assessment of brain imaging findings in ME/CFS, helping distinguish genuine disease markers from isolated observations. Identifying consistent neurobiological abnormalities could eventually support objective diagnosis and guide development of targeted treatments. Understanding brain dysfunction may validate ME/CFS as a neurological condition and support patients seeking medical recognition.
Observed Findings
Additional recruitment of brain areas during cognitive tasks was frequently observed across 11 studies from different research teams
Brain stem abnormalities were reported in 9 studies using different neuroimaging methods
Slugish blood oxygen-dependent (BOLD) signal responses to cognitive tasks were consistently reported by multiple independent teams
Reduced serotonin transporters were identified as a consistent observation across research groups
Regional brain hypometabolism (reduced energy use in specific brain areas) was consistently observed by more than two independent research teams
Inferred Conclusions
The brain stem and cognitive task-related brain activity patterns represent the most reproducible neuroimaging markers of ME/CFS across different research groups
Abnormal neurovascular coupling—a mismatch between brain activity and blood oxygen delivery—may be a unifying mechanism underlying ME/CFS neuroimaging abnormalities
Multiple independent research teams have identified consistent brain abnormalities, suggesting these are genuine biological features of ME/CFS rather than artifacts
Remaining Questions
Which specific brain abnormalities are most directly related to ME/CFS symptoms, and do different abnormalities correspond to different symptom profiles?
What This Study Does Not Prove
This review does not establish whether observed brain abnormalities cause ME/CFS symptoms or result from the illness; the direction of causality remains unknown. The study cannot prove these findings apply to all ME/CFS patients, as many studies used small samples and varied diagnostic criteria. It also does not explain the underlying mechanisms or identify which abnormalities might be most useful for clinical diagnosis.
Why do some neuroimaging findings (such as brain volume and cerebral blood flow measures) remain inconsistent across studies—is this due to methodological differences or genuine heterogeneity in the patient population?
Can neuroimaging abnormalities be used to develop objective diagnostic tests or predict treatment response in ME/CFS?
Do these brain abnormalities persist over time, resolve with recovery, or progress with disease duration?