Brain imaging and behaviorJan 9, 2019

Widespread chemical changes in the brain of people with chronic fatigue syndrome measured by whole-brain imaging

Updated Jan 13, 2026

Abstract

Significant differences in brain metabolites were observed in ME/CFS patients, with elevated choline levels in the left anterior cingulate (p < 0.001).

Fifteen women with ME/CFS showed altered brain metabolite ratios compared to healthy controls across 47 brain regions.
Elevated choline levels were noted in the left anterior cingulate, indicating potential neuroinflammation.
Increased brain temperature was measured in the right insula, putamen, frontal cortex, thalamus, and cerebellum in ME/CFS patients (all p < 0.05).
Brain temperature increases were linked to elevated lactate levels in the right insula, right thalamus, and cerebellum (all p < 0.05).
Metabolite ratios in seven brain regions correlated with fatigue levels in ME/CFS patients (p < 0.05).

Simplified

Previous neuroimaging studies have detected markers of neuroinflammation in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Magnetic Resonance Spectroscopy (MRS) is suitable for measuring brain metabolites linked to inflammation, but has only been applied to discrete regions of interest in ME/CFS. We extended the MRS analysis of ME/CFS by capturing multi-voxel information across the entire brain. Additionally, we tested whether MRS-derived brain temperature is elevated in ME/CFS patients. Fifteen women with ME/CFS and 15 age- and gender-matched healthy controls completed fatigue and mood symptom questionnaires and whole-brain echo-planar spectroscopic imaging (EPSI). Choline (CHO), myo-inositol (MI), lactate (LAC), and N-acetylaspartate (NAA) were quantified in 47 regions, expressed as ratios over creatine (CR), and compared between ME/CFS patients and controls using independent-samples t-tests. Brain temperature was similarly tested between groups. Significant between-group differences were detected in several regions, most notably elevated CHO/CR in the left anterior cingulate (p < 0.001). Metabolite ratios in seven regions were correlated with fatigue (p < 0.05). ME/CFS patients had increased temperature in the right insula, putamen, frontal cortex, thalamus, and the cerebellum (all p < 0.05), which was not attributable to increased body temperature or differences in cerebral perfusion. Brain temperature increases converged with elevated LAC/CR in the right insula, right thalamus, and cerebellum (all p < 0.05). We report metabolite and temperature abnormalities in ME/CFS patients in widely distributed regions. Our findings may indicate that ME/CFS involves neuroinflammation.

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Widespread chemical changes in the brain of people with chronic fatigue syndrome measured by whole-brain imaging

Abstract

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