Project Summary. Anorexia nervosa (AN) is a behavioral disorder marked by self-starvation and fear of weight gain. Weight restoration to a BMI of 19-21 remains the mainstay of treatment for severe AN despite relapse rates in the first year of up to 50%. The mechanisms underlying these high relapse rates remain unknown. Meal- associated anxiety is a striking feature in patients with AN. As the disorder develops, eating behaviors are in- creasingly driven by what appears to be a conditioned avoidance of energy dense foods, known as fear foods, suggesting that exposure-based approaches to treatment may help drive remission. However, in many intensive treatment programs, tube feeding over meal-based nutrition is increasingly the approach. Thus, the need is great for determining what mechanisms and approaches underly the successful treatment of AN and what neurobehavioral factors render individuals responsive versus resistant to treatment. Research: Ex- periments will address the extent to which habituation of learned aversions to fear foods following meal-based exposure generalizes across similar types of foods (Aim 1). Task-based fMRI combined with this behavioral approach will allow the determination of the neural substrates of habituated anxiety responses (Aim 2a). Finally, a machine-learning approach will be used to predict anxiety ratings based on baseline neural activation and identify individuals responsive vs resistant to treatment (Aim 2b). By demonstrating the significance of addressing food-related anxiety as a primary treatment target and examining the neural circuitry activated by fear foods, this project has potential to 1) alter how AN is treated across multiple levels of care and social eating settings, and 2) enhance understanding of the neurobiology that sustains treatment refractoriness. Career Development: The training plan will provide the PI with a) clinically relevant training in the phenomenology of AN, clinical course, and validated instruments used to assess eating disorders important to formulating clinically relevant hypotheses and data interpretation, b) hands-on training in advanced statistical methods for fMRI data, c) opportunity to integrate her training in factors that influence food choice with obtained results, and d) training in grant writing and career development to launch an independent research career. Environment: Johns Hopkins is an excellent environment for collaborative, interdisciplinary, and translational research in healthy and disease states and is focused on mentoring junior faculty. The Johns Hopkins Hospital is ranked #1 in the nation for Psychiatry, with the School of Medicine being the leading research medical institution in the United States and the Eating Disorder Program nationally recognized as a leading program for eating disorder treatment. Career Goal: The proposed research and training program is targeted to meet the PI's overall career goal of becoming an independent academic researcher i...