The influence of aerobic exercise on consolidation of fear extinction learning in PTSD

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PROJECT SUMMARY Exposure-based psychotherapies (e.g., prolonged exposure) are among the best supported treatments for posttraumatic stress disorder (PTSD), yet remission rates for these front-line treatments are typically only 50- 60%. These therapies aim to reduce anxiety towards trauma reminders by enabling therapeutic safety learning, which is hypothesized to work via the mechanisms of fear extinction learning. As such, fear extinction paradigms are widely used as laboratory models of exposure therapy, under the notion that treatments that enhance extinction learning and recall in the lab may be promising candidates for improving the efficacy of exposure-based therapies. Results from our recent clinical pilot studies (without an imaging component) provided preliminary evidence suggesting moderate-intensity aerobic exercise can boost consolidation of fear extinction memories and enhance cognitive indices of extinction recall – an effect that was mediated by exercise-induced increases in anandamide (AEA; a primary endocannabinoid). Thus, this K01 project involves a randomized controlled fMRI laboratory study to: 1) test whether different doses of aerobic exercise (light-, moderate-, and high-intensity) delivered after extinction training improves cognitive, physiological, and neural indices of extinction recall including enhanced retrieval of multivariate patterns of extinction memory encoding (when tested 24hrs later), and 2) further probe the role of AEA by determining dose-response relationships between aerobic exercise intensities and peripheral AEA concentrations (and whether the exercise-induced increases in AEA mediate the aforementioned relationships) in trauma-exposed men and women with and without PTSD (N=120). The PI will receive training and mentorship including: 1) training in computational neuroscience theory and statistical techniques (e.g., multivariate imaging analyses and computational modeling to analyze psychophysiological and neuroimaging data), 2) clinical exposure and expertise in clinical models and neurocircuitry of PTSD and anxiety disorders, 3) gaining expertise in clinical trials to be able to design, conduct, and analyze pharmacological and non-pharmacological RCTs as an independent investigator, and 4) professional and career development activities to foster multi-disciplinary research collaborations. The proposed training and research will occur at The University of Texas at Austin and includes domestic and international collaborations with top-notch researchers, all of which have established extensive NIH research portfolios spanning several fields such as: computational neuroscience, psychiatry, clinical psychology, biostatistics, and pharmacology. Ultimately, the guidance and training experiences gained from the PI’s mentorship team, and the results obtained from this K01 award, will serve as a scaffolding for the PI to become an independent investigator capable of conducting impactful mental health research in PTSD and clinical anxiety populations by utilizing a multidisciplinary lens and advanced methodologies from the ever-advancing fields of psychiatry and computational neuroscience.