Neurocircuitry of OCD: Effects of Modulation

项目摘要（摘要） 整体 该中心的总体目标是进一步了解和探索强迫症的神经网络中心 强迫症（OCD）和网络中与受损的 行为灵活性，反映在持续的回避，一个关键的临床特征的疾病。吻侧 和背侧前扣带皮层（rACC和dACC）、眶额皮层（OFC）、腹外侧前额叶皮层（Ventrolateral prefrontal cortex （vlPFC），纹状体和纹状体与强迫症的异常有关，是强迫症的皮质节点 网络（OCDnet）。中心假说认为，行为的可容忍性反映在持续回避， 强迫症是强迫症网络（OCDnet）中中央节点之间回路功能障碍的结果。我们共同 将使用多模式，跨物种的网络方法来实现3个总体目标：1。识别皮层区域 在OCDnet内，将电路连接交叉链接到其他节点; 2.了解如何损害 导致持续回避的行为灵活性与强迫症患者的这些联系有关 与健康对照受试者相比;以及3.研究调制对这些回路和行为的影响， 可靠性。具体而言，目标1将使用动物研究（P1，2）和人体研究（P1，3， 核心B、C）用于从解剖学、生理学和行为学上表征OCDnet电路;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 OCDnet的异常（P2-4，核心B-D）; Aim 3将使用以下方法调节OCD患者的OCDnet 常规治疗（P4）和直接回路操作（P5）（核心B-D）。总的来说，这些研究 这将进一步加深我们对与强迫症有关的关键大脑区域的回路相互作用的理解， 导致与强迫症相关的持续回避的行为能力，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.