Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy

  • Christina Mueller
  • Joanne C. Lin
  • Sulaiman Sheriff
  • Andrew A. Maudsley
  • Jarred W. YoungerEmail author


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.


Neuroinflammation Chronic fatigue syndrome Magnetic resonance spectroscopy Anterior cingulate Brain temperature Metabolites 



This work was supported by the Solve ME/CFS Initiative [Ramsay Award program]; and the National Institutes of Health [grant number EB016064]. Participant recruitment and Dr. Younger’s effort was supported by NIH-NIAID [grant number AI107655]. The sponsors had no involvement in the study design; in the collection, analysis or interpretation of data; in the writing of the report; or in the decision to submit the article for publication.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Christina Mueller
    • 1
  • Joanne C. Lin
    • 1
  • Sulaiman Sheriff
    • 2
  • Andrew A. Maudsley
    • 2
  • Jarred W. Younger
    • 1
    Email author
  1. 1.Department of PsychologyThe University of Alabama at BirminghamBirminghamUSA
  2. 2.Department of Radiology, Miller School of MedicineUniversity of MiamiMiamiUSA

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