Cortico-striatal-thalamic loop as a neural correlate of neuroticism in the mind-body interface

Seishu Nakagawa, Hikaru Takeuchi, Yasuyuki Taki, Rui Nouchi, Yuka Kotozaki, Takamitsu Shinada, Tsukasa Maruyama, Atsushi Sekiguchid, Kunio Iizuka, Ryoichi Yokoyama, Yuki Yamamoto, Sugiko Hanawa, Tsuyoshi Araki, Carlos Makoto Miyauchi, Daniele Magistro, Kohei Sakaki, Hyeonjeong Jeong, Ryuta Kawashima

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number110590
JournalJournal of Psychosomatic Research
Publication statusPublished - 2021 Oct
Externally publishedYes


  • Cortico-striatal-thalamic loop
  • Mean diffusivity
  • Neuroticism
  • Posterior limb of the internal capsule

ASJC Scopus subject areas

  • Clinical Psychology
  • Psychiatry and Mental health


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