Distinct Processing of Aversive Experience in Amygdala Subregions

Abstract

BackgroundThe 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. MethodsWe used functional magnetic resonance imaging in 39 healthy volunteers with varying levels of trait anxiety to assess distinct contributions of the basolateral amygdala (BLA) and centromedial amygdala to anticipation and experience of aversive events. Additionally, we examined the relationship between any identified functional subspecialization and measures of subjective reported aversion and trait anxiety. ResultsOur results show that the centromedial amygdala 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, high trait-anxious individuals were characterized by indiscriminately heightened BLA activity in response to aversive cues, regardless of actual threat level. ConclusionsOur 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.