Open Access Highly Accessed Research article

Mechanisms underlying fatigue: a voxel-based morphometric study of chronic fatigue syndrome

Tomohisa Okada1, Masaaki Tanaka2, Hirohiko Kuratsune3, Yasuyoshi Watanabe2 and Norihiro Sadato14*

Author Affiliations

1 National Institute for Physiological Sciences, 38 Nishigonaka, Myodaiji, Okazaki, Aichi 444-8585, Japan

2 Department of Physiology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan

3 Department of Health Science, Faculty of Health Science for Welfare, Kansai University of Welfare Sciences, Kashihara, Osaka 582-0026, Japan

4 JST/RISTEX, 2-5-1 Atago, Minato-ku, Tokyo 105-6218, Japan

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BMC Neurology 2004, 4:14  doi:10.1186/1471-2377-4-14

Published: 4 October 2004



Fatigue is a crucial sensation that triggers rest, yet its underlying neuronal mechanisms remain unclear. Intense long-term fatigue is a symptom of chronic fatigue syndrome, which is used as a model to study the mechanisms underlying fatigue.


Using magnetic resonance imaging, we conducted voxel-based morphometry of 16 patients and 49 age-matched healthy control subjects.


We found that patients with chronic fatigue syndrome had reduced gray-matter volume in the bilateral prefrontal cortex. Within these areas, the volume reduction in the right prefrontal cortex paralleled the severity of the fatigue of the subjects.


These results are consistent with previous reports of an abnormal distribution of acetyl-L-carnitine uptake, which is one of the biochemical markers of chronic fatigue syndrome, in the prefrontal cortex. Thus, the prefrontal cortex might be an important element of the neural system that regulates sensations of fatigue.