Putra, Handityo Aulia, Park, Kaechang, Yamashita, Fumio et al. · Neuroimage. Reports · 2022 · DOI
Researchers used brain scans to examine whether the size of certain brain regions relates to how tired people feel, both physically and mentally. In a large group of nearly 1,900 healthy middle-aged adults, they found that specific brain areas showed different sizes depending on fatigue levels—some areas were smaller in people reporting more fatigue, while others were larger. This suggests that brain structure may be connected to how tired we feel, even before someone develops a condition like ME/CFS.
Understanding brain structural changes associated with fatigue in healthy populations may illuminate early mechanisms of fatigue development and provide insights into how ME/CFS-related fatigue could originate. Identifying consistent brain regions involved in fatigue (such as the right SMC) could eventually lead to biomarkers for early detection and prevention strategies. This research bridges healthy fatigue physiology and pathological fatigue conditions, relevant for understanding disease progression.
This study does not prove that brain volume changes *cause* fatigue—it only shows correlation, and causation could work in reverse or involve confounding factors. The findings in healthy adults may not directly translate to ME/CFS pathophysiology, as chronic disease involves distinct pathological processes. The study cannot establish whether these brain differences emerge before fatigue develops or result from experiencing fatigue.
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
Putra, Handityo Aulia, Park, Kaechang, Yamashita, Fumio, Mizuno, Kei, & Watanabe, Yasuyoshi (2022). Regional gray matter volume correlates to physical and mental fatigue in healthy middle-aged adults.. Neuroimage. Reports. https://doi.org/10.1016/j.ynirp.2022.100128
BibTeX
@article{mecfsatlas-putra-2022-regional-gray,
author = {Putra, Handityo Aulia and Park, Kaechang and Yamashita, Fumio and Mizuno, Kei and Watanabe, Yasuyoshi},
title = {Regional gray matter volume correlates to physical and mental fatigue in healthy middle-aged adults.},
journal = {Neuroimage. Reports},
year = {2022},
doi = {10.1016/j.ynirp.2022.100128},
note = {PubMed: 40567574},
url = {https://www.mecfsatlas.com/evidence/putra-2022-regional-gray},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-25. https://www.mecfsatlas.com/evidence/putra-2022-regional-gray
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