Regional brain structure at the intersection of novelty-seeking trait and anxiety

The relationship between novelty-seeking and anxiety is complex. Individuals with a tendency for seeking new experiences (novelty-seeking bias) often navigate a delicate balance between their inherent curiosity and apprehension derived from anxiety. In this study, we investigated brain substrates mediating the relationship between novelty-seeking and anxiety by testing for differences in the grey matter (GM) structure. For this purpose, we applied voxel-based (VBM) and source-based morphometry (SBM) to imaging data from 50 healthy participants, looking, for the first time, at the relationship between regional GM volume and novelty-seeking, anxiety, and their interaction. On its own novelty-seeking bias (as quantified using the Tridimensional Personality Questionnaire) did not correlate with regional GM structure in both analyses. Trait anxiety (quantified using the State-Trait Anxiety Inventory (STAI)) correlated with increased subcallosal gyrus volume in the VBM analysis and was negatively associated with 2 components identified in the SBM analysis which mainly included temporal and frontal regions (i.e., left inferior temporal gyrus, inferior frontal gyrus, middle temporal gyrus, left middle frontal gyrus). Interaction between novelty-seeking score and anxiety score, was expressed in GM volume within the left inferior frontal gyrus (LIFG) in the VMB analysis. There was no suprathreshold interaction with the components identified using SBM. Together, this study provides new insight into the relationship between reward-related decision-making and anxiety. Within the left inferior frontal gyrus, GM volume reflected the interaction of novelty-seeking and anxiety, extending previous research that links lower left inferior frontal gyral volume to reduced impulsivity with increased harm avoidance and anxiety. Our findings suggest this as a possible candidate region for patient stratification and target for intervention in anxiety.