Control and Reward Circuits as Targets for Repetitive Thoughts and Behaviors

描述(由申请人提供)：认知控制和奖赏处理被假设为在具有重复思想/行为的障碍中受损，包括强迫症(OCD)、抽动症和进食障碍(神经性厌食症和神经性暴食症)。本R01建议使用多模式成像来调查这两个RDoC结构背后的神经电路功能障碍是如何导致这些病理行为的，使用OCD作为模型系统(见下文原因)。它还将研究在成功地进行暴露和仪式预防(EX/RP)治疗后，这些回路如何改变。短期目标是阐明基于回路的异常是如何导致重复性的 想法/行为；这些数据将为未来的跨诊断研究提供信息。长期目标是识别认知控制和奖赏回路的异常，这些异常可能成为新的跨诊断治疗的目标。具体地说，多模式成像(fMRI、静息状态功能连接和扩散张量成像)将用于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、连接和组织在40名未服用药物的强迫症成年人(年龄18-45岁)与40名健康对照组(目标1和2)之间有何不同。强迫症患者在EX/RP治疗8周后的基于回路的变化将与健康对照组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，从而检查大脑异常与行为表现和临床表型之间的联系。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)认知控制和奖赏加工的缺陷被认为是这种疾病核心的重复思想/行为的基础；2)控制和奖赏回路的功能异常已被报道；以及3)EX/RP是一种有效的治疗方法，可导致某些患者的临床缓解。这允许调查行为的正常化是否导致这些电路的正常化。如果是的话， 这些回路异常可能成为治疗发展的新靶点。这种方法--利用多模式成像来了解电路功能，使用多个分析单元，并将治疗作为测试大脑-行为关系的实验工具--与NIMH的RDoC项目和战略计划一致。重复的思想/行为是各种疾病的特征，会导致功能障碍和生活质量下降；因此，了解这些症状背后的大脑机制并确定治疗开发的新靶点可以促进公共健康。

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.