PROJECT SUMMARY/ABSTRACT Anorexia nervosa (AN) is the deadliest of all mental illnesses and is associated with significant medical consequences and functional impairment. Despite significant research efforts, the etiology of the disorder remains unknown, and outcomes from existing psychological treatments remain suboptimal. Some prior work in AN has suggested alterations in decision-making, sensitivity to risk, and altered activity in frontostriatal circuits may be involved in the maintenance of the disorder. However, this work has been mixed in its findings, likely secondary to limited consideration of subcomponents of decision-making and/or relevant contextual influences on this process. Drawing from work in behavioral economics and computational neuroscience, alongside clinical evidence that many outcomes related to food and weight are uncertain/ambiguous, we propose that the decision- making profile of individuals with AN may be better characterized by ambiguity aversion, such that a sensitivity toward ambiguous outcomes interrupts successful value-based decision-making and results in maintenance of dietary restraint despite significant functional and personal cost. To test this hypothesis, we will gather behavioral choice and neural data from females with AN, restricting type (n=65, ages 16-22) and healthy control (HC) subjects (n=65) while completing a well-validated decision-making task that allows separation of risky and ambiguous decisions. Additionally, the AN group will provide measures of symptoms at baseline and 6-month follow-up to explore how performance on the task relates to the persistence of symptoms. We hypothesize that the AN group will demonstrate increased ambiguity aversion compared to HC and choice behavior inconsistent with prevailing models of value-based decision-making (Aim 1). On the neural level, we expect that, compared to HC, individuals with AN will demonstrate differential activation in frontostriatal regions during ambiguous trials, rather than risk (Aim 2). Lastly, we expect that neural and behavioral parameters gauging ambiguity aversion will relate to BMI, dietary restriction, and cognitive symptoms of AN both cross-sectionally and over time, such that individuals demonstrating greater aversion to ambiguous decisions will have lower body weights and greater engagement in symptoms, supporting our hypothesized maintenance mechanism (Aim 3). Overall, the current project will provide an important next step toward a more precise characterization of the cognitive profile of individuals with AN. In pursuing this knowledge, consistent with the goal of the R15 AREA award, the current project will simultaneously provide graduate and undergraduate students at Hofstra University with invaluable hands-on experiences in neuroimaging, computational methods, and clinical research.

PROJECT NARRATIVE Outcomes from gold-standard treatments for anorexia nervosa (AN) remain suboptimal, secondary to incomplete characterization of biobehavioral processes that may maintain symptoms. Using neuroimaging and computational methods, the current project will explore decision-making processes under conditions of risk and uncertainty in females with AN, restricting type, and matched healthy controls. The data from this project will provide critical insights into the neural substrates of altered cognition in AN that can be used to revise maintenance models for the disorder and design more precisely targeted interventions.