Control and Reward Circuits as Targets for Repetitive Thoughts and Behaviors

描述（由申请人提供）：假设认知控制和奖励处理在重复性思维/行为障碍中受损，包括强迫症（OCD），妥瑞氏综合征和饮食障碍（神经性厌食症和神经性贪食症）。本R01建议使用多模态成像来研究这两种RDoC结构下的神经回路功能障碍如何导致这些病理行为，并将强迫症作为模型系统（见下文）。它还将研究这些回路如何在暴露和仪式预防（EX/RP）成功治疗后发生变化。短期目标是阐明基于回路的异常如何导致重复

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.