Neurocircuitry of OCD: Effects of Modulation

 描述（由申请人提供）：该中心的总体目标是进一步了解强迫症（OCD）的神经网络中心以及与该疾病相关的网络内的异常。具体来说，我们将使用 多模式，网络方法：1。定位特定区域和连接它们的通路，这些区域和通路在疾病中被改变; 2.确定神经调节对回路连接性的影响;以及3.利用这些数据来开发一种非侵入性的个体化治疗方法。为了了解强迫症的网络基础，我们使用一种多维的方法，结合解剖学（神经元水平的结构分析）与全球活动和连接模式（扩散和功能性MRI）来表征强迫症电路功能异常的关键连接，以及神经调节后的网络变化。我们的中心假设是，强迫症的特点是杏仁核/腹内侧前额叶皮层和背侧前扣带回（dACC）和眶额皮层（OFC）之间的超连通性，以及dACC/OFC和背外侧和腹外侧前额叶皮层之间的连接减少。这种情绪和认知控制系统之间平衡的变化导致背侧纹状体的活动状态增强。我们还认为，活动异常的结构基础围绕着特定的皮层区域（或节点），这些区域将情感相关区域与认知控制相关区域联系起来。此外，我们预测这些节点的位置在个体之间的变异性。最后，我们假设调制的电路将返回连接配置文件相对正常的水平。这些研究将为探索新的治疗靶点提供翻译连接。由于这个网络与广泛的精神疾病有关，包括抑郁症，创伤后应激障碍，成瘾，因此产生的数据将产生远远超出强迫症的影响。

 DESCRIPTION (provided by applicant): The overall goal of this Center is to further our understanding of the neural network central to obsessive compulsive disorder (OCD) and the abnormalities within that network that are associated with the disease. Specifically, we will use a multimodal, network approach to: 1. localize specific regions and the pathways that connect them that are altered in the disease; 2. determine the effects of neuromodulation on the connectivity of the circuit(s); and 3. use these data to develop a non-invasive approach for individualized treatment. To understand the network underlying OCD, we use a multidimensional approach combining anatomy (structural analysis at the neuronal level) with global patterns of activity and connectivity (diffusion and functional MRI) to characterize the critical connections that underlie functional abnormalities in the OCD circuit, and the network changes following neuromodulation. Our central hypothesis is that OCD is characterized by hyperconnectivity between the amygdala/ventromedial prefrontal cortex and dorsal anterior cingulate (dACC) and orbitofrontal cortex (OFC), and decreased connectivity between dACC/OFC and dorsolateral and ventrolateral prefrontal cortex. This change in balance between emotion and cognitive control systems results in a heightened activity state in the dorsal striatum. We also posit that the structural basis for abnormalities in activity center aroun specific cortical regions (or nodes) that connect emotion-associated regions with those involved in cognitive control. Furthermore, we predict variability in the position of these nodes across individuals. Finally, we hypothesize that modulation of the circuit will return connectivity profils to relatively normal levels. The studies will provide a translational link to probe novel therapeutc targets. As this network has been linked to a wide range of psychiatric disorders including, depression, post-traumatic stress disorder, addictions, the resulting data will have implications that extend well beyond OCD.