Sustained anxiety increases amygdala-dorsomedial prefrontal coupling: a mechanism for maintaining an anxious state in healthy adults

Background: Neuroimaging research has traditionally explored fear and anxiety in response to discrete threat cues (e. g., during fear conditioning). However, anxiety is a sustained aversive state that can persist in the absence of discrete threats. Little is known about mechanisms that maintain anxiety states over a prolonged period. Here, we used a robust translational paradigm (threat of shock) to induce sustained anxiety. Recent translational work has implicated an amygdala-prefrontal cortex (PFC) circuit in the maintenance of anxiety in rodents. To explore the functional homologues of this circuitry in humans, we used a novel paradigm to examine the impact of sustained anticipatory anxiety on amygdala-PFC intrinsic connectivity. Methods: Task-independent fMRI data were collected in healthy participants during long-duration periods of shock anticipation and safety. We examined intrinsic functional connectivity. Results: Our study involved 20 healthy participants. During sustained anxiety, amygdala activity was positively coupled with dorsomedial PFC (DMPFC) activity. High trait anxiety was associated with increased amygdala-DMPFC coupling. In addition, induced anxiety was associated with positive coupling between regions involved in defensive responding, and decreased coupling between regions involved in emotional control and the default mode network. Limitations: Inferences regarding anxious pathology should be made with caution because this study was conducted in healthy participants. Conclusion: Findings suggest that anticipatory anxiety increases intrinsic amygdala-DMPFC coupling and that the DMPFC may serve as a functional homo-logue for the rodent prefrontal regions by sustaining anxiety. Future research may use this defensive neural context to identify biomarkers of risk for anxious pathology and target these circuits for therapeutic intervention.