Neurocircuitry of OCD: Effects of Modulation

项目摘要(摘要) 总括 该中心的总体目标是进一步了解和探索强迫症的核心神经网络 强迫症(OCD)和该网络中与受损相关的异常 行为灵活性体现在持续的回避上，这是该病的一个关键临床特征。主席台 和背侧前扣带回皮质(rACC和dACC)，眶前叶皮质(OFC)，腹外侧额叶皮质 VLPFC、脑岛和纹状体与强迫症的异常相关，是强迫症的皮质结节。 网络(OCDnet)。中心假设是，在持续回避中反映出的行为僵化 强迫症是强迫症网络(OCDnet)中心节点之间回路功能障碍的结果。作为集体，我们 将使用多模式、跨物种的网络方法来实现3个主要目标：1.识别皮质区域 在OCDnet内交叉连接到其他节点的电路；2.了解 导致持续性回避的行为灵活性与强迫症患者的这些联系有关 与健康对照受试者比较；以及3.研究调制对这些回路和行为的影响 僵化。具体地说，目标1将使用动物研究(P1，2)和人体研究(P1，3， 核心B、C)从解剖、生理和行为上描述OCDnet电路的特征；目标2将 描述新开发的概率接近回避任务PAAT中的损伤如何与 强迫症患者的强迫症网络异常(P2-4，核心B-D)；AIM 3将利用 常规治疗(P4)和直接电路操作(P5)(核心B-D)。总的来说，这些研究 将进一步加深我们对涉及强迫症的关键脑区的电路相互作用的理解，它们参与了 导致与强迫症相关的持续回避的行为僵化，以及 这些回路的神经调节。

Project Summary (Abstract) Overall The overall goal of this Center is to further understand and probe the neural network central to obsessive compulsive disorder (OCD) and the abnormalities within that network that are associated with impaired behavioral flexibility that is reflected in persistent avoidance, a key clinical feature of the disease. The rostral and dorsal anterior cingulate cortex (rACC and dACC), orbitofrontal cortex (OFC), ventrolateral prefrontal cortex (vlPFC), insula and the striatum are associated with abnormalities in OCD and are the cortical nodes in the OCD network (OCDnet). The Center hypothesis is that the behavioral inflexibility reflected in persistent avoidance in OCD is the result of circuit dysfunction between central nodes in the OCD network (OCDnet). Collectively we will use a multimodal, cross-species network approach to achieve 3 overarching aims: 1. Identify cortical regions within the OCDnet that cross-link circuit connections to other nodes; 2. Understand how impairments in behavioral flexibility that results in persistence avoidance are associated with these connections in OCD patients compared to healthy control subjects; and 3. Study the effects of modulation on these circuits and on behavioral inflexibility. Specifically, Aim 1 will use a combination of animal studies (P1, 2), and human studies (P1, 3, Cores B, C) to characterize the OCDnet circuits anatomically, physiologically, and behaviorally; Aim 2 will characterize how impairments in a newly developed probabilistic approach avoidance task PAAT are linked to the abnormalities in the OCDnet (P2-4, Core B-D); and Aim 3 will modulate the OCDnet in OCD patients using both conventional treatments (P4) and direct circuit manipulations (P5) (Cores B-D). Collectively, these studies will further our understanding of circuit interactions of key brain regions implicated in OCD, their involvement in behavioral inflexibility that results in persistent avoidance associated with OCD, and the effects of neuromodulation of those circuits.