Physical activity, endocannabinoids, and model-based decision making in PTSD

About This Grant

PROJECT SUMMARY Decision making has a profound impact on how we interact with the world. For instance, adults with posttraumatic stress disorder (PTSD) often form inaccurate beliefs about their environment leading to flawed decision-making and missed opportunities (e.g., the world is a dangerous place and therefore I should not leave my house to attend a social gathering). In fact, a major goal of cognitive processing therapy (CPT) in PTSD involves identifying and modifying traumatic beliefs and cognitive biases that impair decision-making. This process typically involves promoting more complex learning in which individuals form an abstract representation of the environment which allows them to make prospective predictions about likely outcomes based on different choices (termed model- based learning). Greater engagement in model-based learning is thought to provide individuals with more flexibility and allow more adaptive learning and decision-making – which overlaps with major treatment targets in CPT. As such, manipulations that can boost model-based learning may prove to play an important role in enhancing important cognitive processes of CPT – an efficacious treatment with room for improvement (~50- 60% remission rate). We recently demonstrated that an acute 30-minute bout of moderate-vigorous intensity aerobic exercise promoted model-based over model-free learning during decision making in adults with and without PTSD. However, it remains unknown whether habitual physical activity levels (as opposed to a single laboratory exercise session) also influence model-based decision-making and whether such a relationship between physical activity and model-based decision-making may also be mediated by candidate biomarkers that are sensitive to physical activity and involved in reward-based learning and decision-making (e.g., endocannabinoids). As such, the purpose of this study is to determine whether and how engagement in regular physical activity is associated with model-based decision-making (under threat and non-threat conditions). In line with this R03 mechanism, we propose a self-contained study that will utilize computational modeling and assess physical activity behaviors, candidate biomarkers, and performance on a commonly administered lab- based decision-making task (i.e., two-stage Markov task) capable of discriminating model-free from model-based decision-making in adult men and women with and without PTSD (N=90) over a 3-week period. The results from this study may have significant clinical implications and improve our understanding of the potential for incorporating physical activity into the treatment of PTSD and will be instrumental for the design and development of subsequent randomized-controlled trials. This study will be executed by a multi-disciplinary team that has an extensive history of conducting studies aimed at improving our understanding of the psychobiological mechanisms responsible for the effects of physical activity on cognitive processes in adults with and without PTSD.