DESCRIPTION (provided by applicant): Cognitive control and reward processing are hypothesized to be impaired in disorders with repetitive thoughts/behaviors, including obsessive-compulsive disorder (OCD), Tourette's Syndrome, and eating disorders (anorexia nervosa and bulimia nervosa). This R01 proposes to use multimodal imaging to investigate how dysfunction in neural circuits underlying these two RDoC constructs contributes to these pathological behaviors, using OCD as a model system (see reasons below). It will also examine how these circuits change following successful treatment with exposure and ritual prevention (EX/RP). The short-term goal is to clarify how circuit-based abnormalities contribute to repetitive thoughts/behaviors; these data will inform future transdiagnostic studies. The long-term goal is to identify abnormalities in cognitive control and reward circuits that could be targets for new transdiagnostic treatments. Specifically, multimodal imaging (fMRI, resting state functional connectivity, and diffusion tensor imaging) will be used to determine how the function, connectivity, and organization of the overlapping frontostriatal circuits that support cognitive control and reward processing differ across 40 unmedicated adults with OCD (ages 18-45) compared to 40 healthy control subjects (Aims 1 & 2). Circuit-based changes in OCD patients following 8 weeks of EX/RP treatment will be compared to non-specific changes in the healthy control group (Aim 3). All participants will complete self- reports, clinical interviews, and additional behavioral tasks of cognitive control and reward processing, allowing examination of how brain abnormalities link to behavioral performance and clinical phenotype. OCD provides a unique model system to address these aims because: 1) deficits in cognitive control and reward processing are hypothesized to underlie the repetitive thoughts/behaviors at the core of this disorder; 2) functional abnormalities in both control and reward circuits have been reported; and 3) EX/RP is an effective therapy that leads to clinical remission in some. This allows investigation of whether normalization of behavior leads to normalization of these circuits. If so, these circuit abnormalities could become new targets for treatment development. This approach-- leveraging multimodal imaging to understand circuit function, employing multiple units of analysis, and using treatment as an experimental tool to test brain-behavior relationships --is consonant with NIMH's RDoC Project and Strategic Plan. Repetitive thoughts/behaviors are hallmarks of various disorders and lead to functional impairment and reduced quality of life; thus understanding the brain mechanisms that underlie these symptoms and identifying new targets for treatment development can advance public health.

PUBLIC HEALTH RELEVANCE: This project will use different brain imaging methods to investigate how dysfunction in brain circuits underlying cognitive control and reward processing might contribute to pathological repetitive thoughts and behaviors, using obsessive-compulsive disorder (OCD) as a model system. The long-term goal is to identify brain markers that could be new targets for treatment. As repetitive thoughts/behaviors characterize various disorders (e.g., OCD, Tourette's Syndrome, eating disorders, autism) and lead to functional impairment and reduced quality of life, understanding the brain mechanisms that underlie these symptoms and identifying new targets for treatment can advance public health.