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具有重复思想/行为的障碍中受损，包括强迫症（OCD）、图雷特综合征和进食障碍（神经性厌食症和神经性贪食症）。该R 01建议使用多模态成像来研究这两个RDoC结构背后的神经回路功能障碍如何促成这些病理行为，使用OCD作为模型系统（见下文原因）。它还将研究这些电路如何改变后，成功的治疗与曝光和仪式预防（EX/RP）。短期目标是阐明基于电路的异常如何有助于重复性 这些数据将为未来的transdiagnosis研究提供信息。长期目标是识别认知控制和奖励回路中的异常，这些异常可能成为新的转诊断治疗的目标。 具体而言，将使用多模态成像（fMRI，静息状态功能连接和扩散张量成像）来确定支持认知控制和奖励处理的重叠额纹状体回路的功能，连接和组织如何在40名未经药物治疗的强迫症成人（年龄18-45岁）与40名健康对照受试者之间存在差异（目的1和2）。将在EX/RP治疗8周后强迫症患者中基于回路的变化与健康对照组中的非特异性变化进行比较（目标3）。所有参与者将完成自我报告、临床访谈以及认知控制和奖励处理的额外行为任务，从而检查大脑异常如何与行为表现和临床表型联系起来。强迫症提供了一个独特的模型系统来解决这些目标，因为：1）认知控制和奖励处理的缺陷被假设为这种疾病核心的重复思想/行为的基础; 2）控制和奖励回路的功能异常已被报道; 3）EX/RP是一种有效的治疗方法，在某些情况下可导致临床缓解。这允许调查行为的正常化是否导致这些回路的正常化。如果是这样的话， 这些回路异常可能成为治疗开发的新目标。 这种方法-利用多模态成像来理解电路功能，采用多个分析单元，并使用治疗作为实验工具来测试大脑-行为关系-与NIMH的RDoC项目和战略计划一致。重复的想法/行为是各种疾病的标志，并导致功能障碍和生活质量下降;因此，了解这些症状的大脑机制并确定治疗开发的新目标可以促进公共卫生。

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.