Distinct processing of aversive experience in amygdala subregions

Abstract

Background The amygdala is an anatomically complex medial temporal brain structure whose subregions are considered to serve distinct functions. However, their precise role in mediating human aversive experience remains ill understood. Methods We used functional MRI in 39 healthy volunteers with varying levels of trait anxiety to assess distinct contributions of the basolateral (BLA) and centromedial amygdala (CMA) to anticipation and experience of aversive events. Additionally, we examined the relationship between any identified functional subspecialisation and measures of subjective reported aversion and trait anxiety. Results Our results show that the CMA is responsive to aversive outcomes, but insensitive to predictive aversive cues. In contrast, the BLA encodes an aversive prediction error that quantifies whether cues and outcomes are worse than expected. A neural representation within the BLA for distinct threat levels was mirrored in self-reported subjective anxiety across individuals. Furthermore, trait-anxious individuals were characterised by indiscriminately heightened BLA activity in response to aversive cues, irrespective of actual threat level. Conclusions Our results demonstrate that amygdala subregions are distinctly engaged in processing of aversive experience, with elevated and undifferentiated BLA responses to threat emerging as a potential neurobiological mediator of vulnerability to anxiety disorders