Altered Functional Coupling of the Bed Nucleus of the Stria Terminalis and Amygdala in Spider Phobic Fear.

Abstract

Background: Individuals with spider phobic (SP) fear show hypervigilance and amygdala hyperactivity toward fear-associated stimuli, which may promote the development of other anxiety disorders. The amygdala is a key region within the fear network, which is connected to the anxiety system, where the bed nucleus of the stria terminalis (BNST) plays a crucial role. However, the BNST's involvement in phobic fear is unknown. Therefore, this study investigated the association of phobic fear and anxiety on these regions' functional connectivity (FC) in SP compared to healthy controls (HC). Methods: 7T-functional MRI resting-state FC of 30 individuals with SP and 45 HC was assessed to detect network differences between these groups. The association of phobic fear severity, trait anxiety, and social anxiety on FC was explored using linear regressions combined with seed-to-voxel analyses with amygdala and BNST as primary seeds, corrected for age and sex. Results: In SP, phobic fear was associated with reduced FC between the left amygdala and the right supramarginal gyrus. In contrast, anxiety severity was related to increased FC between the right BNST and the left inferior frontal gyrus. Moreover, social anxiety was related to decreased FC between bilateral BNST and left precuneus. Conclusions: These findings show changes in FC in SP, connecting fear with altered activity in the BNST and amygdala. The results suggest that persistent anxiety in phobic fear is associated with abnormal brain function in these regions, potentially explaining susceptibility to anxiety disorders and processes involved in phobic fear, such as threat perception, avoidance, and salience. Impact statement This is the first study to report altered FC mechanisms of BNST and amygdala in individuals with SP using 7T ultra-high field resting-state data. So far, only distinct characterization of brain regions, especially of BNST and amygdala, involved in those disorders exists. Our results contribute to closing this knowledge gap by providing the first evidence that deviant BNST and amygdala function in SP might elucidate the susceptibility to other anxiety disorders.