PROJECT SUMMARY/ABSTRACT Over 43M Americans (~13% of the population) will suffer from social anxiety disorder in their lifetime (Kessler et al., 2012) – 20M of which will have fear of public speaking (Kessler et al., 1998). Cognitive-behavioral therapy (a major component of which is exposure therapy) is a leading treatment for social anxiety disorder but is only fully effective in ~45% of individuals (Loerinc, et al., 2015). Exposure therapy is the clinical proxy of Pavlovian extinction in which the individual approaches their feared situation (e.g., social situation) without the expected aversive outcome (e.g., negative social judgment). Several basic research findings show that stronger reward processing is linked to better extinction of fear, suggesting that enhancing reward processing can improve exposure therapy. First, reward processing is involved in extinction learning at the time of omission of an expected aversive outcome, such that the omission is experienced as “relief-pleasantness” as measured by self- report and by neural mechanisms of reward processing (e.g., Lange, et al., 2020). Second, direct stimulation of the reward circuitry has been shown to enhance extinction of fear (Sierra, et al., 2023). Third, low self-reported reward processing is associated with low relief-pleasantness (Leng, et al., 2022). Fourth, social anxiety disorder is associated with poor reward processing (Cremers, et al., 2015). Lastly, anhedonia – a robust correlate of poor reward processing and social anxiety – is associated with poor extinction of fear (Young, et al., 2021). Thus, enhancing reward processing may be especially likely to improve exposure therapy outcomes in social anxiety disorder (Aim 1) by increasing relief-pleasantness when an expected aversive event does not occur (Aim 2). In this K23, we will conduct the first experimental therapeutics study investigating the effects of target engagement (reward processing) on subsequent exposure therapy outcome (social anxiety; specifically, fear of public speaking). To this end, socially anxious participants with a fear of public speaking and low reward processing will undergo the behavioral portion of Positive Affect Treatment (PAT-B) or Relaxation Treatment; both treatments are expected to decrease negative affect, but PAT-B is expected to improve reward processing more than Relaxation Treatment (Craske et al., 2023). Subsequently, all participants will undergo Exposure Therapy for fear of public speaking with the primary outcome being multi-modal assessment of public speaking anxiety. For experimental therapeutics, the target is reward processing, which we will measure primarily as relief- pleasantness in fMRI fear conditioning during extinction at the time of electric shock omission (measured neurally and with computational modeling of self-report relief-pleasantness). The training plan will help the Candidate gain expertise in experimental therapeutics, fMRI, and computational modeling in the service of his career goal: to improve our understanding and treatment of anxiety disorders. This K23 may improve the efficacy of exposure therapy, our understanding of its mechanisms, and help millions of people with social anxiety disorder.

Project Narrative Over 43 million Americans (~13% of the population) will suffer from social anxiety disorder at some point in their lives (Kessler, et al., 2012), but a leading form of treatment (cognitive-behavioral therapy, a major component of which is exposure therapy) is only fully effective in approximately 45% of individuals (Loerinc, et al., 2015). Critically, based on robust basic scientific research in the animal and human literatures, there is strong reason to believe that improving reward processing will enhance i) relief-pleasantness when an expected aversive outcome does not occur, ii) Pavlovian extinction of fear, and iii) exposure therapy outcome. In this K23, we will investigate the effects of Positive Affect Treatment (designed to increase reward processing) vs Relaxation Treatment (control condition) on subsequent exposure therapy outcome (fear of public speaking) for socially anxious individuals who have a fear of public speaking and low reward processing while measuring the treatment mechanism (reward processing) before, during, and after treatment.