The overall goal of this Mentored Patient-Oriented Research Career Development (K23) Award is to 1. Provide the applicant with the skills to perform independent functional magnetic resonance brain imaging (fMRI) research in Eating Disorders, specifically Restricting Type Anorexia Nervosa (RAN), 2. Train the applicant in novel Neurocomputational Modeling approaches that link psychological theory with underlying neural substrates, and 3. Extend our knowledge on brain activity in RAN in relation to food and non-food (monetary) reward processing.
Aim 1 . a. is to investigate the functionality of anteroventral striatum reward pathways using fMRI and a paradigm of expected and unexpected delivery of sweet taste stimuli (O'Doherty et al 2003). We hypothesize that women Recovered from and III with RAN will have reduced anteroventral striatum activation compared to control women.
In Aim 1. b., using computational models for reward conditioning on the fMRI data, we expect reduced reward learning signals in III and Recovered RAN in the anteroventral striatum compared to controls.
Aim 2. a. is to investigate if reduced orbitofrontal cortex and striatum activation compared to CW exists in III and Recovered RAN in response to monetary immediate reward (Tanaka et al 2004). In contrast we expect III and recovered RAN to have greater activation than controls in the dorsolateral prefrontal and parietal cortex during delayed monetary reward (Tanaka et al 2004).
In Aim 2. b., using computational models on the acquired brain data, we expect in III and Recovered RAN reduced anteroventral striatum immediate, but increased dorsal striatum delayed reward processing compared to controls. This study uses novel technologies and paradigms. It will both advance the field of Eating Disorders research greatly as well as will be an excellent opportunity to provide the applicant with training in fMRI and Neurocomputational Modeling. The applicant will be mentored by renowned experts in the field of Eating Disorders, fMRI Brain Imaging and Neurocomputational Modeling, and he will attend courses in the Cognitive Science and Psychology Program at the University of Colorado. Anorexia Nervosa has the highest mortality among all psychiatric disorders. This application will help identify pathways of disturbance of the reward system in Restricting type AN, will provide new insight into the disease mechanism, and will provide us with new information for the development of advanced treatments.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Mentored Patient-Oriented Research Career Development Award (K23)
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Adult Psychopathology and Disorders of Aging Study Section (APDA)
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Chavez, Mark
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University of Colorado Denver
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Shott, M E; Cornier, M-A; Mittal, V A et al. (2015) Orbitofrontal cortex volume and brain reward response in obesity. Int J Obes (Lond) 39:214-21
McFadden, Kristina L; Tregellas, Jason R; Shott, Megan E et al. (2014) Reduced salience and default mode network activity in women with anorexia nervosa. J Psychiatry Neurosci 39:178-88
Filoteo, J Vincent; Paul, Erick J; Ashby, F Gregory et al. (2014) Simulating category learning and set shifting deficits in patients weight-restored from anorexia nervosa. Neuropsychology 28:741-51
Frank, Guido K; Shott, Megan E; Hagman, Jennifer O et al. (2013) Alterations in brain structures related to taste reward circuitry in ill and recovered anorexia nervosa and in bulimia nervosa. Am J Psychiatry 170:1152-60
Frank, Guido K W (2013) An 11-year-old boy with Asperger's disorder presenting with aggression. Am J Psychiatry 170:963-6
Mettler, Lisa N; Shott, Megan E; Pryor, Tamara et al. (2013) White matter integrity is reduced in bulimia nervosa. Int J Eat Disord 46:264-73
Frank, Guido K W (2013) Altered brain reward circuits in eating disorders: chicken or egg? Curr Psychiatry Rep 15:396
Frank, Guido K W; Shott, Megan E; Hagman, Jennifer O et al. (2013) Localized brain volume and white matter integrity alterations in adolescent anorexia nervosa. J Am Acad Child Adolesc Psychiatry 52:1066-1075.e5
Oberndorfer, Tyson A; Frank, Guido K W; Simmons, Alan N et al. (2013) Altered insula response to sweet taste processing after recovery from anorexia and bulimia nervosa. Am J Psychiatry 170:1143-51
Frank, Guido K W; Kaye, Walter H (2012) Current status of functional imaging in eating disorders. Int J Eat Disord 45:723-36

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