Abstract
BACKGROUND: Though a key symptom underlying many anxiety disorders is hypervigilant threat monitoring, its biological bases in humans remain poorly understood. Animal models suggest that anxious processes such as hypervigilant threat monitoring are distinct from cued fear-like responses and mediated by the bed nucleus of the stria terminalis (BNST). Here, we applied psychophysiological and neuroimaging methodologies sensitive to sustained arousal-based responses to test the role of the human BNST in mediating environmental threat monitoring, a potential experimental model for sustained anxiety symptoms. METHODS: Healthy participants (n = 50) with varying trait anxiety performed an environmental threat-monitoring task during functional magnetic resonance imaging where a stimulus line continuously fluctuated in height, providing information relevant to subsequent risk for electric shocks. Skin conductance was collected in a separate cohort (n = 47) to validate task-evoked modulation of physiological arousal. RESULTS: A forebrain region consistent with the BNST showed greater overall recruitment and exaggerated tracking of threat proximity in individuals with greater anxiety. The insular cortex tracked threat proximity across all participants, showed exaggerated threat proximity responding with greater anxiety, and showed enhanced recruitment when threat proximity was ostensibly controllable. CONCLUSIONS: Activity in the BNST and insula continuously monitored changes in environmental threat level and also subserved hypervigilant threat-monitoring processes in more highly trait anxious individuals. These findings bridge human and animal research informing the role of the BNST in anxious-related processes. In addition, these findings suggest that continuous functional magnetic resonance imaging paradigms offer promise in further elucidating the neural circuitries supporting sustained anticipatory features of anxiety.