Centromedial amygdala is more relevant for phobic confrontation relative to the bed nucleus of stria terminalis in patients with spider phobia.

Recent studies indicate differential involvement of the centromedial amygdala (CM) and the bed nucleus of the stria terminalis (BNST) during processing (anticipation and confrontation) of threat stimuli. Here, temporal predictability was shown to be a relevant factor. In this study, we want to investigate the relevance of these effects, which were found in healthy subjects, for anxiety disorders. Therefore, we investigated the differential involvement of CM and BNST in the anticipation and confrontation of phobic stimuli under variation of temporal predictability in spider phobia. 21 patients with spider phobia and 21 healthy controls underwent a temporally predictable/unpredictable phobic and neutral anticipation and confrontation paradigm using functional magnetic resonance imaging (fMRI) and ROI analyses. During the anticipation phase, healthy controls showed higher CM and BNST activity during the predictable compared with the unpredictable condition compared with the anxiety patients. During a confrontation phase that followed the anticipation phase, CM was more activated than BNST during the phobic compared with the neutral confrontation. While this effect was independent of threat predictability in patients, healthy controls showed higher activation in the CM compared with the BNST only during the predictable spider confrontation compared with the predictable bird confrontation. The results contribute to a better understanding of the separate roles of the CM and BNST during phobic processes. The CM was found to be more relevant to phobic confrontation in patients with spider phobia compared with the BNST.

BNST and amygdala activation to threat: Effects of temporal predictability and threat mode.

Recent animal and human studies highlight the uncertainty about the onset of an aversive event as a crucial factor for the involvement of the centromedial amygdala (CM) and bed nucleus of the stria terminalis (BNST) activity. However, studies investigating temporally predictable or unpredictable threat anticipation and confrontation processes are rare. Furthermore, the few existing fMRI studies analyzing temporally predictable and unpredictable threat processes used small sample sizes or limited fMRI paradigms. Therefore, we measured functional brain activity in 109 predominantly female healthy participants during a temporally predictable-unpredictable threat paradigm, which aimed to solve limited aspects of recent studies. Results showed higher BNST activity compared to the CM during the cue indicating that the upcoming confrontation is aversive relative to the cue indicating an upcoming neutral confrontation. Both the CM and BNST showed higher activity during the confrontation with unpredictable and aversive stimuli, but the reaction to aversive confrontation relative to neutral confrontation was stronger in the CM compared to the BNST. Additional modulation analyses by NPSR1 rs324981 genotype revealed higher BNST activity relative to the CM in unpredictable anticipation relative to predictable anticipation in T-carriers compared to AA carriers. Our results indicate that during the confrontation with aversive or neutral stimuli, temporal unpredictability modulates CM and BNST activity. Further, there is a differential activity concerning threat processing, as BNST is more involved when focussing on fear-related anticipation processes and CM is more involved when focussing on threat confrontation.