Network-based mapping and neurotransmitter architecture of brain gray matter correlates of extraversion.

Objective: To identify common functional brain networks underlying heterogeneous gray matter (GM) correlates of extraversion and to characterize the neurotransmitter receptor and transporter architecture associated with these networks.

Methods: A systematic literature search identified 13 voxel-based morphometry (VBM) studies reporting GM correlates of extraversion in healthy individuals (N = 1,478). Functional connectivity network mapping (FCNM) approach using normative resting-state functional MRI data from the Human Connectome Project (HCP, N = 1,093) mapped divergent GM correlates extraversion onto common networks. Robustness was assessed via replication using an independent Southwest University Adult Lifespan Dataset (SALD, N = 329) and sensitivity analyses varying seed radii. Spatial relationships between the identified brain networks and the distribution of major neurotransmitter receptors/transporters were subsequently characterized using the JuSpace toolbox.

Results: FCNM analysis revealed that reported GM correlates of extraversion converge onto specific functional networks. Spatial overlap analysis showed the highest association with the frontoparietal network (FPN) (37.32%) and the default mode network (DMN) (32.99%). Furthermore, JuSpace analysis indicated that these extraversion-linked networks exhibited significant positive spatial correlations with 5-hydroxytryptamine receptor 2A (5HT2a; p = 0.021, r = 0.215), cannabinoid receptor type-1 (CB1; p = 0.005, r = 0.392), and metabotropic glutamate receptor 5 (mGluR5; p = 0.01, r = 0.330), and negative correlations with the norepinephrine transporter (NAT; p = 0.018, r = -0.221) and serotonin transporter (SERT; p = 0.023, r = -0.201).

Conclusion: Despite regional heterogeneity in prior VBM studies, structural GM correlates of extraversion consistently map onto the DMN and FPN. This network-based approach reconciles previous inconsistencies and highlights the importance of these large-scale networks as a plausible functional substrate underlying structural variations associated with extraversion. These findings advance a systems-level understanding of the neural basis of this core personality dimension and suggest a distinct neurochemical architecture within these networks.