Learning about location-dependent threat: neural abnormalities in clinical anxiety

Abstract Anxiety disorders are characterized by maladaptive defensive responses to distal or uncertain threats. Elucidating neural mechanisms of anxiety is essential to formulate new treatment strategies tartgeting these circuits. In an fMRI scanner, patients with pathological anxiety (ANX, n=23) and healthy comparisons (HC, n=28) completed a contextual threat learning paradigm, in which they picked flowers in a virtual environment comprising a danger zone in which flowers were paired with shock and a safe zone (no shock). ANX compared with HC showed 1) global decreased ventromedial prefrontal cortex and anterior hippocampus activation during the task, 2) increased insula and dorsomedial prefrontal cortex activation in the danger zone during the task; and 3) increased amygdala and midbrain/periaqueductal gray activation in the danger zone prior to potential shock delivery. Our findings suggest that ANX exhibit a heightened reactivity to threat and show decreased activation in modulatory areas responsible for regulating context-appropriate emotional responses.