Uncovering the correlation between neurotransmitter-specific functional connectivity and multidimensional anxiety in a non-clinical cohort.

Abstract

Research on anxiety faces challenges due to the wide range of symptoms, making it difficult to determine if different aspects of anxiety are linked to distinct neurobiological processes. Both alterations in functional brain connectivity (FC) and monoaminergic neurotransmitter systems are implicated as potential neural bases of anxiety. We aimed to investigate whole-brain FC involving monoaminergic nuclei and its association with anxiety dimensions in 178 non-clinical participants. Nine anxiety-related scales were used, encompassing trait and state anxiety scores, along with measures of cost-probability, hypervigilance, reward-punishment sensitivity, uncertainty, and trait worry. Resting-state functional magnetic resonance imaging data were acquired, focusing on seven brainstem regions representing serotonergic, dopaminergic, and noradrenergic nuclei, with their FC patterns voxel-wise correlated with the scales. All models underwent family-wise-error correction for multiple comparisons. We observed intriguing relationships: trait and state anxiety scores exhibited opposing correlations in FC between the dorsal raphe nucleus and the paracingulate gyrus. Additionally, we identified shared neural correlates, such as a negative correlation between the locus coeruleus and the frontal pole. This connection was significantly associated with scores on measures of probability, hypervigilance, reward sensitivity, and trait worry. These findings underscore the intricate interplay between anxiety dimensions and subcortico-cortical FC patterns, shedding light on the underlying neural mechanisms governing anxiety.