Neural Bases of Disgust Conditioning in Anorexia Nervosa

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PROJECT SUMMARY/ABSTRACT This K23 application aims to support Dr. Lisa Anderson to achieve her overarching goal of establishing an independent, patient-oriented research career that will (a) elucidate biological and psychological mechanisms associated with risk and maintenance of eating disorders, and (b) use this information to develop and optimize precise, efficacious treatments for eating disorders. The proposed application will strengthen Dr. Anderson’s abilities to meet her career goals by providing advanced training designed to: (a) develop expertise in theory and assessment of disgust conditioning mechanisms involved in transdiagnostic models psychopathology characterized by avoidance behaviors, and to translate this knowledge to research for eating disorders; (b) gain knowledge and skills in neuroimaging methods necessary to conduct independent research investigating the neural substrates of disordered eating; and (c) obtain advanced training in analysis of neuroimaging (fMRI) data required to independently examine maintenance mechanisms underlying eating disorders across various units of measurement (i.e., psychological-, behavioral-, physiological-, and neurobiological-level variables). Dr. Anderson has assembled a team of experts who will provide training to accomplish the proposed training goals and scientific aims. The core mentorship team consists of Dr. Scott Crow (training in translational eating disorders research), Dr. Kathryn Cullen (neuroimaging training), Dr. Mark Fiecas (biostatistics), Dr. Shmuel Lissek (cross-diagnostic models of disgust learning), and Dr. Thomas Hildebrandt (translation of disgust learning models to eating disorders, computational modeling of aversive reinforcement learning in anorexia nervosa [AN]). Dr. Kelvin Lim will consult on neuroimaging study design and R01 application preparations. Dr. Carol Peterson will consult on emotion regulation models and emotion-based mechanisms research for eating disorders. Dr. Josh Cisler will consult on disgust-based task design and computational models of aversive reinforcement learning. As part of her training, Dr. Anderson will complete a two-part study. Study 1a will compare patterns in neural activation during a food-specific disgust generalization and extinction task between individuals with AN and non-eating-disorder comparison participants to establish the extent to which the neural substrates of food-specific disgust generalization and extinction specifically relate to food avoidance and restrictive eating severity in AN. In a longitudinal arm, Study 1b will determine the extent to which neural activation patterns associated with disgust generalization and extinction predict later AN maintenance. Overall, in addition to supporting Dr. Anderson’s training goals, this project will meet a critical need by identifying disgust conditioning mechanisms that may underlie food avoidance symptom severity and disorder maintenance in AN. This knowledge will ultimately inform the development of novel biological treatments (e.g., psychopharmacology, neuromodulation) and optimization of psychological interventions (e.g., reinforcement- based psychotherapies) that promote long-term recovery from this persistent psychiatric disorder.