The functioning of overlapping frontostriatal circuits in children with OCD

描述（由申请人提供）：强迫症（OCD）是一种致残性疾病，通常始于儿童期并持续到成年期。神经影像学研究表明，在强迫症的额纹状体电路的解剖和功能障碍，但很少有研究评估这些电路在儿童（儿童发病）的强迫症，这可能是一个独特的强迫症亚型，符合发展变化的功能和结构的前额叶皮层的功能。我们假设重叠的额纹状体回路功能障碍通过损害对侵入性想法（强迫症）和重复性行为（强迫症）的控制以及降低处理奖励的能力而导致强迫症。过度依赖早期发育的纹状体会让强迫行为变成习惯。在这个R21中，我们将使用fMRI来评估30名未服药的强迫症儿童（6-12岁）与30名年龄匹配的健康对照组的这些回路的功能。将使用经过充分验证的Simon任务评估背侧额纹状体控制系统的功能。支持习惯学习和奖励处理的背侧纹状体和腹侧额纹状体回路的功能将 使用一种新的功能磁共振成像范式进行评估，该范式直接类似于用于定义啮齿动物中基于奖励的学习系统的神经基础的任务，该任务针对MRI扫描仪内的虚拟现实环境进行定制。这一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。我们还将评估同一儿童的背侧和腹侧额纹状体回路的功能连接，并确定这些重叠回路的干扰是否与强迫症症状的严重程度相关。在强迫症的这些电路的功能障碍的识别将支持未来的纵向研究，他们的神经发育轨迹强迫症。我们的长期目标是确定一种独特的大脑异常模式，这是强迫症的基础，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，并且与NIMH促进大脑发现的战略计划一致。

DESCRIPTION (provided by applicant): Obsessive-Compulsive Disorder (OCD) is a disabling illness that typically begins in childhood and persists into adulthood. Neuroimaging studies suggest anatomical and functional disturbances of frontostriatal circuits in OCD but few studies have assessed the functioning of these circuits in pediatric (child-onset) OCD which is likely a distinct OCD subtype, coinciding with developmental changes in the function and structure of the prefrontal cortex. We hypothesize that dysfunction in overlapping frontostriatal circuits contributes to OCD by impairing control over intrusive thoughts (obsessions) and repetitive behaviors (compulsions) and diminishing the capacity to process rewards. An over-reliance on the earlier developing striatum then allows compulsions to become habits. In this R21, we will use fMRI to assess the functioning of these circuits in 30 unmedicated children with OCD (ages 6-12) compared to 30 age-matched healthy controls. The functioning of dorsal frontostriatal control systems will be assessed using the well-validated Simon task. Functioning of the dorsal striatum and ventral frontostriatal circuits that support habit learning and reward processing will be assessed using a novel fMRI paradigm directly analogous to tasks used to define the neural bases of reward-based learning systems in rodents, 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. We will also assess functional connectivity in dorsal and ventral frontostriatal circuits in the same children, and determine whether disturbances in these overlapping circuits are associated with OCD symptom severity. Identification of dysfunction in either of these circuits in OCD will support future longitudinal study of their neurodevelopmental trajectories in OCD. Our long-term goal is to identify a distinct pattern of brain abnormalities tht underlies OCD 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.