ORIGINAL RESEARCH article
Front. Syst. Neurosci.
This article is part of the Research TopicSpatial and Regional Mapping of Brain Neural CommunicationView all 4 articles
Network-based mapping and neurotransmitter architecture of gray matter correlates of neuroticism
Provisionally accepted
- 1Nantong University, Nantong, China
- 2Binhai Maternal and Child Health Hospital, Yancheng, China
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Objective: Although neuroticism is a major risk factor for adverse health outcomes, its neural basis is obscured by inconsistent findings from studies of regional gray matter volume (GMV) correlates. This study sought to identify convergent functional brain networks underlying these heterogeneous GMV correlates using functional connectivity network mapping (FCNM), and to explore their neurochemical basis. Methods: We systematically identified 10 voxel-based morphometry (VBM) studies (N = 1595) reporting neuroticism-associated GMV coordinates. Using resting-state fMRI data from 1093 healthy Human Connectome Project participants, FCNM was applied to map functional connectivity patterns associated with these coordinates. Overlap with canonical networks was assessed. The Juspace toolbox explored spatial relationships between identified networks and major neurotransmitter receptor distributions. Results: Despite spatial heterogeneity, neuroticism-related GMV changes consistently mapped onto three principal functional networks: the default mode network (DMN), frontoparietal network (FPN), and ventral attention network (VAN). These mappings were robust across varied analytical parameters. Moreover, the implicated networks demonstrated significant spatial correlation with the distributions of 5-hydroxytryptamine receptor 2A (5-HT2A), cannabinoid receptor type 1 (CB1), and metabotropic glutamate receptor 5 (mGluR5). Conclusions: Despite regional variability, GMV correlates of neuroticism converge on common large-scale brain networks involved in self-referential processing, cognitive control, and salience processing. Their significant spatial coupling with 5-HT2A, CB1, and mGluR5 receptor distributions suggests serotonergic, endocannabinoid, and glutamatergic modulatory mechanisms contributing to network-level alterations. This cross-modal and network-based approach provides a unified framework for understanding the biological substrates of neuroticism, reconciling prior inconsistencies, and identifying key targets for prevention or biomarker development.
Keywords: Default Mode Network, frontoparietal network, functional connectivity network mapping, gray matter, neuroticism, ventral attention network
Received: 29 Sep 2025; Accepted: 10 Dec 2025.
Copyright: © 2025 Wang, Hucheng, Sun, Zhang, Dai, Pan and Gu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
PingLei Pan
Si-Yu Gu
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