Regional gray matter volume correlates to physical and mental fatigue in healthy middle-aged adults

Previous studies on neural/molecular mechanisms of fatigue focused on a variety of brain functions, morphological changes, and neurochemical functions such as neurotransmitter and neuroimmune dynamics. However, MRI morphological changes were adopted primarily to compare patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and healthy controls. A few studies have been done on healthy subjects with fatigue scores; one study with 63 adults (their ages of 53.2 ± 8.3) showed the gray matter volume (GMV) reduction in good correlation with a higher score of fatigue. The other one with university students (their ages of 20.7 ± 1.8) demonstrated no significant correlation between regional GMV (rGMV) and fatigue severity. To elucidate the brain structural underpinning in parallel with fatigue development, a large number of healthy middle-aged adults (n = 1873; aged 54.1 ± 5.4) without ME/CFS were recruited, and the correlation between both rGMV in the cerebrum including basal ganglia and Chalder's fatigue questionnaire (CFQ) with physical and mental categories were investigated. A higher CFQ score denotes a higher perceived fatigue level by the participant. The physical fatigue scores of CFQ showed a significantly negative correlation (i.e., smaller rGMV for higher CFQ score) with the volume of the right planum temporale and supplemental motor cortex (SMC), while the left putamen, middle temporal gyrus (MTG), parietal operculum, and right precentral gyrus showed a significantly positive correlation (i.e., bigger rGMV for higher CFQ score). In the mental fatigue scores, the right SMC and left lateral orbital gyrus (LOG) showed a significantly negative correlation, while only the left fusiform gyrus showed a significantly positive correlation. In total scores of (both physical and mental) fatigue, the right SMC and orbital part of the inferior frontal gyrus (OIFG) showed a negative correlation, while the left putamen and MTG showed a positive correlation. Therefore, the right SMC may play a critical role in fatigue progression because of the only common factor among physical, mental, and total fatigue. The left putamen may play a compensatory role with a positive correlation to physical and total fatigue. Additionally, identifying the other gray matter regions that positively or negatively correlated to CFQ of healthy adults may help deepen the understanding of early-stage fatigue progression, leading to the future establishment of preventive measures through volumetrics by using MRI.