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Updated: Oct 24, 2025

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Published on: March 14, 2025
Cortico-striatal-thalamic loop as a neural correlate of neuroticism in the mind-body interface
Seishu Nakagawa1, Hikaru Takeuchi2, Yasuyuki Taki3
1Division of Psychiatry, Tohoku Medical and Pharmaceutical University, Sendai, Japan; Department of Human Brain Science, Institute of Development, Ageing and Cancer, Tohoku University, Sendai, Japan.
Objective:
Although brain structural studies have demonstrated the neural correlates of neuroticism, the outcomes are not easily identified because of the various possible brain regions involved, low statistical power (low number of subjects), and brain structural measures available, such as mean diffusivity (MD), which are more suitable than standard regional measures of grey and white-matter volume (rGMV, rWMV) and fractional anisotropy (FA). We hypothesized that neuroticism neural correlates could be detected by MD and differentially identified using other measures. We aimed to visualize the neural correlates of neuroticism.
Methods:
A voxel-by-voxel regression analysis was performed using the MD, rGMV, rWMV, or FA value as the dependent variable and with neuroticism scores based on the NEO-FFI and its confounding factors as independent variables in 1207 (693 men and 514 women; age, 20.7 ± 1.8, 18-27 years), non-clinical students in a cross-sectional study.
Results:
MD in the cortico- (orbitofrontal cortex, anterior cingulate cortex, and posterior insula) striatal- (caudate and putamen) thalamic loop regions, including the right posterior limb of the internal capsule, were positively associated with neuroticism using the threshold-free cluster enhancement method with a family-wise error-corrected threshold of P < 0.0125 (0.05/4, Bonferroni correction for four types of MRI data [MD, rGMV, rWMV, and FA]) at the whole-brain level.
Conclusions:
An increased MD has generally been associated with reduced neural tissues and possibly area function. Accordingly, this finding helps elucidate the mechanism of somatization in neuroticism because the regions related to neuroticism are considered neural correlates of somatoform disorders.
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