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.