An FMRI Study of Three Neural Systems Implicated in Obsessive-Compulsive Disorder

描述（由申请人提供）：强迫症（OCD）是一种致残疾病，通常始于青春期，持续到成年。我们假设强迫症是由于支持自我调节控制过程的额纹状体脑回路功能障碍，这些障碍影响背纹状体内的刺激反应“习惯”学习系统和内侧颞叶区域内的陈述性记忆系统，这些系统是中皮质边缘奖励处理系统的组成部分。在本R21中，我们将使用功能磁共振成像来评估30名未接受药物治疗的强迫症成年人（18-45岁）与30名年龄匹配的健康对照者这三个神经系统的功能（主要目的）。额纹状体控制系统的功能将使用经过充分验证的西蒙任务进行评估。习惯学习和奖励处理系统的功能将使用一种新的fMRI范式进行评估，该范式直接类似于用于定义动物研究中学习和记忆系统的神经基础的任务，该范式针对MRI扫描仪内的虚拟现实环境进行定制。这种范式为强迫症的脑功能研究提供了一种转化神经科学方法。扫描后，强迫症患者将接受12周的5 -羟色胺再摄取抑制剂（SRI）开放治疗，我们将探索我们的基线fMRI测量是否能预测SRI反应（次要目标）。识别强迫症患者任何神经系统的功能异常（生物特征）将支持未来的研究，以调查这些大脑异常的发生和进展以及治疗效果。如果这些异常与治疗反应相关，这些fMRI范式可能成为强迫症的有效生物标志物。我们的长期目标是确定强迫症背后的大脑异常的独特模式和/或预测治疗反应，并开发直接针对这些异常的新治疗方法。通过验证使用特定的fMRI范式来检查强迫症潜在的大脑机制，这项R21应用是朝着这个方向迈出的第一步，并且与NIMH促进大脑发现和识别治疗反应的生物标志物的战略计划是一致的。

DESCRIPTION (provided by applicant): Obsessive-Compulsive Disorder (OCD) is a disabling illness that typically begins in adolescence and persists into adulthood. We hypothesize that OCD is due to dysfunction in frontostriatal brain circuits that subserve self-regulatory control processes, and that these disturbances affect stimulus-response 'habit' learning systems within the dorsal striatum and declarative memory systems within medial temporal lobe regions that are components of a mesocorticolimbic reward processing system. In this R21, we will use fMRI to assess the functioning of these three neural systems in 30 unmedicated adults with OCD (ages 18-45) compared to 30 age-matched healthy controls (Primary Aim). The functioning of frontostriatal control systems will be assessed using the well-validated Simon task. The functioning of habit learning and reward processing systems will be assessed using a novel fMRI paradigm directly analogous to tasks used to define the neural bases of learning and memory systems in animal research, tailored to a virtual reality environment within the MRI scanner. This paradigm provides a translational neuroscience approach to the study of brain function in OCD. After scanning, OCD patients will be offered 12 weeks of open treatment with a serotonin reuptake inhibitor (SRI), and we will explore whether our baseline fMRI measures predict SRI response (Secondary Aim). Identification of functional abnormalities (a biosignature) in any of these neural systems in OCD will support future studies to investigate the onset and progression of these brain abnormalities and the effects of treatment. If these abnormalities are associated with treatment response, these fMRI paradigms could become valid biomarkers for OCD. Our long-term goal is to identify a distinct pattern of brain abnormalities that underlies OCD and/or predicts treatment response, and to develop novel treatments that target these abnormalities directly. By validating the use of specific fMRI paradigms to examine potential brain mechanisms underlying OCD, this R21 application is a first step in this direction and consistent with the NIMH strategic plan to promote brain discovery and to identify biomarkers of treatment response.