Characterizing abnormalities in the OCD neural network

项目摘要 强迫症(OCD)影响着2%-3%的人口，以强迫症为特征， 干扰人际和职业功能的侵犯性思想和强迫行为， 有时到了很严重的程度。考虑到强迫症的生物标记物的迫切需要 神经生物学过程并为治疗选择提供靶点，满足这一需求的一种方法是 推测强迫症患者特定的神经网络功能和结构异常 与这种疾病有关。我们最重要的假设是，有一个功能失调的神经网络 强迫症，这可能与过度仪式化行为的发展有关 描述这种疾病的特征。该神经网络包括背侧前扣带回皮质、眶前叶皮质、 腹外侧额叶皮质、背外侧前额叶皮质、腹内侧前额叶皮质、杏仁核和 背侧纹状体。因此，该拟建中心的项目2(P2)的首要目标是确定关键的休息 状态功能连接异常，和潜在脑白质异常，在这个回路中 患有强迫症的成年人。我们将使用功能磁共振成像来检查这些区域之间的静息状态连接，以及扩散 成像和概率纤维束造影术检查连接这些区域的纤维束中的白质 强迫症患者。我们将使用最先进的垫片例程来优化 这个神经网络中的区域。因此，P2旨在检查40例未用药/SRI/氯丙咪嗪用药 成人强迫症与40名健康成年人(年龄18-35岁)：1.静息状态连接，以提供 衡量这些区域之间的“主要”功能连通性。2.这些之间的白质连接 地区。3.我们还将确定这些静息状态连接性指标与 神经网络中的白质更好地理解结构和功能之间的整合 此网络中的连接。P2与中心的其他项目一起，将通知理解 功能和脑白质连接异常的上述神经网络在强迫症，并将提供 神经生物学措施，最终为治疗选择和疾病的新治疗方法提供信息。

Project Summary Obsessive compulsive disorder (OCD) affects 2-3% of the population and is characterized by obsessional, obtrusive thoughts and compulsive behaviors, that interfere with interpersonal and occupational function, sometimes to a severe extent. Given the critical need for biomarkers of OCD to inform underlying neurobiological processes and provide targets for treatment choices, one way forward to meet this need is to identify in individuals with OCD specific functional and structural abnormalities in neural networks putatively associated with the illness. Our overarching hypothesis is that there is a neural network that is dysfunctional in OCD, and that this may be associated with development of the excessive ritualized behaviors that characterize the illness. This neural network includes dorsal anterior cingulate cortex, orbitofrontal cortex, ventrolateral prefrontal cortex, dorsolateral prefrontal cortex, ventromedial prefrontal cortex, amygdala and dorsal striatum. The overarching goal of Project 2 (P2) in this proposed center is thus to identify key resting state functional connectivity abnormalities, and abnormalities in underlying white matter, in this circuitry in adults with OCD. We will use fMRI to examine resting state connectivity among these regions, and diffusion imaging and probabilistic tractography to examine white matter in tracts connecting these regions in individuals with OCD. We will use state of the art shimming routines to optimize the signal: noise ratio in regions in this neural network. P2 thereby aims to examine in 40 unmedicated/SRI/clomipramine medicated adults with OCD versus 40 healthy adults (aged 18-35 years): 1. Resting state connectivity, to provide a measure of “tonic” functional connectivity among these regions. 2. White matter connectivity among these regions. 3. We will also determine relationships between these measures of resting state connectivity and white matter in the neural network to better understand the integration between structural and functional connections in this network. P2, together with other projects in the center, will inform understanding of functional and white matter connection abnormalities in the above neural network in OCD, and will provide neurobiological measures to ultimately inform treatment choice and novel treatments for the illness.