Uncertainty Potentiates Neural and Cardiac Responses to Visual Stimuli in Anxiety Disorders

BACKGROUND: Intolerance of uncertainty and worry about future events are cardinal features of anxiety. However, the neurobiological and physiological mechanisms underlying these characteristics of anxiety remain to be fully elucidated. METHODS: Individuals with diagnosed anxiety disorders (n = 29, 22 female) and age-matched comparison subjects (n = 28, 17 female) completed a task in which pictures (aversive or neutral content) were preceded by cues indicating certainty or uncertainty about the emotional valence of the subsequent pictures. We assessed functional magnetic resonance imaging and heart rate activity with respect to the 1) cue period, 2) emotional valence of the pictures, and 3) modulatory effect of uncertainty on responses to subsequent pictures. RESULTS: Individuals with anxiety disorders and comparison subjects exhibited similar functional magnetic reso-nance imaging and cardiac activity during the cue period and for the aversive versus neutral picture contrast. However, individuals with anxiety disorders exhibited greater modulatory effects of uncertainty on their responses to subsequent pictures. Specifically, they displayed greater functional magnetic resonance imaging activity in a number of cortical regions (visual cortex, anterior cingulate cortex, superior temporal gyrus, and anterior insula), as well as significantly reduced cardiac deceleration to pictures preceded by the uncertainty cue. CONCLUSIONS: These findings suggest that heightened neural and autonomic reactivity to stimuli during conditions of uncertainty may be a key psychobiological mechanism of anxiety.