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

描述(由申请人提供)：强迫症(OCD)是一种致残性疾病，通常从青春期开始，一直持续到成年。我们假设强迫症是由于辅助自我调节控制过程的额纹状体脑回路的功能障碍所致，这些干扰影响背侧纹状体内的刺激反应习性学习系统和内侧颞叶区域的陈述性记忆系统，这些系统是中皮质边缘奖赏处理系统的组成部分。在这项R21中，我们将使用功能磁共振成像来评估30名未服用药物的强迫症成年人(年龄18-45岁)的这三个神经系统的功能，并与30名年龄匹配的健康对照组(主要目标)进行比较。额纹状体控制系统的功能将使用经过充分验证的Simon任务进行评估。将使用一种新的fMRI范式来评估习惯学习和奖励处理系统的功能，该范式直接类似于动物研究中用于定义学习和记忆系统的神经基础的任务，该任务是为MRI扫描仪内的虚拟现实环境量身定做的。这一范式为研究强迫症的脑功能提供了一种翻译神经科学方法。扫描后，强迫症患者将接受为期12周的开放治疗，使用5-羟色胺再摄取抑制剂(SRI)，我们将探索我们的基线fMRI测量是否可以预测SRI反应(二级目标)。在强迫症的任何一个神经系统中发现功能异常(一个生物特征)将支持未来的研究，以调查这些大脑异常的发生和发展以及治疗的效果。如果这些异常与治疗反应有关，这些fMRI范例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型治疗方法。通过验证使用特定的功能磁共振成像范例来检查强迫症潜在的大脑机制，R21的应用是朝着这个方向迈出的第一步，并与NIMH促进大脑发现和确定治疗反应的生物标记物的战略计划一致。 公共卫生相关性：我们建议调查三个神经系统的功能异常，我们假设这些异常是强迫症(OCD)的基础，并探索这些异常是否与OCD的严重程度和/或预测治疗反应有关。识别这些神经系统的异常不仅有助于更好地了解导致强迫症的原因，而且使未来的研究能够检查强迫症患者何时以及如何发生这些大脑异常，并开发直接针对他们的新的治疗方法。

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. PUBLIC HEALTH RELEVANCE: We propose to investigate functional abnormalities in three neural systems that we hypothesize underlie Obsessive-Compulsive Disorder (OCD) and to explore whether these abnormalities are associated with OCD severity and/or predict treatment response. Identification of abnormalities in these neural systems will not only foster a better understanding of what causes OCD, but also enable future studies to examine when and how people with OCD develop these brain abnormalities and to develop novel treatments that directly target them.