UC San Diego

Despite the efficacy of exposure therapy for anxiety, there are individual differences in outcomes that are not well understood. Fear extinction learning, in which a previously feared stimulus is no longer paired with negative outcomes, is the hypothesized mechanism of exposure. Relative to healthy adults, anxious individuals show greater resistance to fear extinction learning and altered amygdala and ventromedial prefrontal cortex (vmPFC) activation. The goals of this dissertation were therefore to test associations between neural bases of fear extinction and (1) anxiety severity, as well as (2) exposure efficacy. Twenty-four adults with public speaking anxiety completed a fear conditioning task during functional magnetic resonance imaging (fMRI). During fear acquisition, one neutral stimulus (CS+) was paired with a loud scream and another (CS-) was presented but never paired. During fear extinction, both CS+ and CS- were presented without any aversive stimulus. In a subsequent exposure session, participants completed four five minute speeches. Finally, participants completed an anxiety assessment by phone two weeks later. Robust regression analyses were used to relate neural correlates of fear extinction learning to baseline anxiety and anxiety reduction following exposure. Ratings of negative valence and arousal to the CS+ increased following fear acquisition and diminished following extinction. Individuals who rated the CS+ more negatively showed greater amygdala activation during acquisition and extinction, and also reported less anxiety reduction following exposure. Individuals with greater baseline anxiety severity had greater activation in dorsomedial PFC. Finally, individuals with greater vmPFC and less amygdala activation during extinction reported greater anxiety reduction from baseline to follow-up. Those individuals who, by self-report and neural activation, demonstrated better extinction learning also reported greater anxiety reduction following an exposure intervention. This is the first time that the theoretical link between extinction learning and exposure efficacy has been demonstrated. The results suggest that individuals whose brain activation dynamically adjusts to the presence or absence of aversive consequences may benefit most from brief exposure therapy, providing an important step toward the mechanistic understanding of exposure. Future work should examine whether fear extinction can reliably predict clinical outcomes and be used as a prognostic test to guide treatment decisions