Mizuno, Kei, Tanaka, Masaaki, Tanabe, Hiroki C et al. · NeuroImage. Clinical · 2015 · DOI
This study looked at how children with ME/CFS use their brains when doing challenging thinking tasks. When performing two tasks at once (like sorting letters while reading a story), children with ME/CFS had to activate much larger areas of their brains compared to healthy children. This suggests their brains work harder and less efficiently to accomplish the same tasks, which may contribute to the exhaustion they experience.
This mechanistic study provides neurobiological evidence that ME/CFS involves inefficient brain processing, offering objective support for patient-reported cognitive difficulties and fatigue. Understanding that the brain must work harder and consume more energy in ME/CFS validates the reality of cognitive impairment and may guide future therapeutic targets aimed at improving neural efficiency.
This study does not prove that increased brain activation causes ME/CFS or that it is the primary dysfunction. It is a correlational study in children only, so findings may not generalize to adults with ME/CFS. The study does not establish whether neural inefficiency is a cause or consequence of the disease, nor does it address underlying mechanisms (mitochondrial dysfunction, immune activation, etc.).
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 →
The first block is for the primary paper and is the citation you should use in research work. The atlas-snapshot line only applies if you are specifically referring to this atlas’s reading of the paper on the date shown.
Primary citation
Mizuno, Kei, Tanaka, Masaaki, Tanabe, Hiroki C, Joudoi, Takako, Kawatani, Junko, Shigihara, Yoshihito, et al. (2015). Less efficient and costly processes of frontal cortex in childhood chronic fatigue syndrome.. NeuroImage. Clinical. https://doi.org/10.1016/j.nicl.2015.09.001
BibTeX
@article{mecfsatlas-mizuno-2015-less-efficient,
author = {Mizuno, Kei and Tanaka, Masaaki and Tanabe, Hiroki C and Joudoi, Takako and Kawatani, Junko and Shigihara, Yoshihito and Tomoda, Akemi and Miike, Teruhisa and Imai-Matsumura, Kyoko and Sadato, Norihiro and Watanabe, Yasuyoshi},
title = {Less efficient and costly processes of frontal cortex in childhood chronic fatigue syndrome.},
journal = {NeuroImage. Clinical},
year = {2015},
doi = {10.1016/j.nicl.2015.09.001},
note = {PubMed: 26594619},
url = {https://www.mecfsatlas.com/evidence/mizuno-2015-less-efficient},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-30. https://www.mecfsatlas.com/evidence/mizuno-2015-less-efficient
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