Amygdala-prefrontal cortex functional connectivity during threat-induced anxiety and goal distraction

Background: Anxiety produced by environmental threats can impair goal-directed processing and is associated with a range of psychiatric disorders, particularly when aversive events occur unpredictably. The prefrontal cortex (PFC) is thought to implement controls that minimize performance disruptions from threat-induced anxiety and goal distraction by modulating activity in regions involved in threat detection, such as the amygdala. The inferior frontal gyrus (IFG), orbitofrontal cortex (OFC), and ventromedial PFC (vmPFC) have been linked to the regulation of anxiety during threat exposure. We developed a paradigm to determine if threat-induced anxiety would enhance functional connectivity between the amygdala and IFG, OFC, and vmPFC.

Methods: Healthy adults performed a computer-gaming style task involving capturing prey and evading predators to optimize monetary rewards while exposed to the threat of unpredictable shock. Psychophysiological recording (n = 26) and functional magnetic resonance imaging scanning (n = 17) were collected during the task in separate cohorts. Task-specific changes in functional connectivity with the amygdala were examined using psychophysiological interaction analysis.

Results: Threat exposure resulted in greater arousal measured by increased skin conductance but did not influence performance (i.e., monetary losses or rewards). Greater functional connectivity between the right amygdala and bilateral IFG, OFC, vmPFC, anterior cingulate cortex, and frontopolar cortex was associated with threat exposure.

Conclusions: Exposure to unpredictable threat modulates amygdala-PFC functional connectivity that may help maintain performance when experiencing anxiety induced by threat. Our paradigm is well-suited to explore the neural underpinnings of the anxiety response to unpredictable threat in patients with various anxiety disorders.