Functional Amygdala-Hippocampus Connectivity During Anticipation of Aversive Events is Associated with Gray's Trait “Sensitivity to Punishment”

Abstract

The reinforcement sensitivity theory postulates a behavioral inhibition system that modulates reaction to stimuli indicating aversive events. Gray's dimension of anxiety, reflecting human trait sensitivity to aversive events, determines the extent to which stimuli activate the behavioral inhibition system. Although structural brain imaging has previously identified the amygdala and the hippocampus as two major components related to the behavioral inhibition system, the functional dynamics of the responses in these structures remain unclear. In this study, we examined the event-related functional magnetic resonance imaging blood oxygen level-dependent response in the hippocampus and amygdala as well as the functional connectivity of the two regions during anticipation of monetary loss in 45 healthy human subjects. Anticipation of loss elicited activation in the hippocampus as well as in the amygdala. Additionally, substantial functional connectivity between the two areas was observed. Furthermore, this functional connectivity was significantly correlated with individual differences in Gray's trait sensitivity to aversive events. Specifically, higher trait sensitivity to aversive events was associated with increased functional connectivity following cues indicating potential loss. In summary, we show that individual differences regarding Gray's trait sensitivity to aversive events as defined by the reinforcement sensitivity theory are associated with the neural dynamics of the amygdala-hippocampal circuit during anticipation of aversive events. In particular, evidence is provided for a relationship between functional brain imaging data and a psychometric approach specifically measuring Gray's trait sensitivity to aversive events, thereby potentially identifying the neural substrate of the behavioral inhibition system.