Neurocircuitry of OCD: Effects of Modulation

强迫症的神经回路：调节的影响

• 批准号: 10411705
• 负责人: Suzanne N Haber
• 金额: $ 318.01万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-01 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10411705
• 关键词: Affect; Anatomy; Animals; Anterior; Area; Aversive Stimulus; Behavior; Behavioral; Brain region; Cells; Chronic; Clinical; Corpus striatum structure; Deep Brain Stimulation; Disease; Dorsal; Evaluation; Fiber; Focused Ultrasound; Frequencies; Functional disorder; Funding; Goals; Human; Image; Impairment; Individual; Insula of Reil; Intervention; Lead; Lesion; Link; Location; Medication Management; Mental disorders; Methods; Neurons; Obsession; Obsessive-Compulsive Disorder; Outcome; Pathway interactions; Patients; Physiological; Physiology; Population; Positioning Attribute; Prefrontal Cortex; Prevention therapy; Probability; Protocols documentation; Rewards; Ritual compulsion; Source; Therapeutic; Ulysses Contracts; Uncertainty; avoidance behavior; base; behavioral impairment; cingulate cortex; conventional therapy; cost; crosslink; efficacious treatment; experimental study; flexibility; high resolution imaging; information processing; multimodality; neural circuit; neural network; neuroregulation; nonhuman primate; response; treatment response; ultrasound; white matter

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.

项目摘要（摘要） 全面的 该中心的总体目标是进一步理解和探测痴迷的神经网络 强迫症（OCD）和该网络中与受损相关的异常 行为灵活性反映在持续避免的情况下，这是该疾病的关键临床特征。 the 背侧扣带回皮层（RACC和DACC），甲状腺皮质（OFC），腹外侧前额叶皮层 （VLPFC），岛菌和纹状体与OCD异常有关，是OCD中的皮质淋巴结 网络（OCDNET）。中心假设是，行为僵硬性反映在持续的避免 强迫症是OCD网络（OCDNET）中心节点之间电路功能障碍的结果。我们集体 将使用多模式的跨物种网络方法来实现3个总体目的：1。识别皮质区域 在OCDNET中，交联电路连接到其他节点； 2.了解如何减值 导致持续避免持续性的行为灵活性与强迫症患者的这些联系有关 与健康对照组相比；和3。研究调制对这些电路和行为的影响 不灵活。具体而言，AIM 1将使用动物研究（P1、2）和人类研究（P1、3， 核B，c）在解剖学，生理和行为上表征Ocdnet电路； AIM 2意志 表征新开发的概率方法中的损害如何避免任务PAAT链接到 OCDNET的异常（P2-4，Core B-D）； AIM 3将使用OCD患者的OCDNET使用 常规处理（P4）和直接电路操作（P5）（核B-D）。总的来说，这些研究 我们将进一步理解与强迫症有关的关键大脑区域的电路相互作用，它们参与 行为僵硬性导致与强迫症相关的持续回避和 这些电路的神经调节。