Neurocircuitry of OCD: Effects of Modulation

 描述(由申请人提供)：该中心的总体目标是促进我们对强迫症(OCD)的核心神经网络以及该网络中与疾病相关的异常的理解。具体来说，我们将使用 多模式、网络方法：1.定位疾病中改变的特定区域和连接它们的路径；2.确定神经调节对电路连通性的影响(S)；以及3.使用这些数据开发一种非侵入性的个性化治疗方法。为了了解强迫症背后的网络，我们使用解剖学(神经元水平的结构分析)与全球活动和连接模式(扩散和功能磁共振)相结合的多维方法来表征强迫症回路中功能异常背后的关键连接，以及神经调节后的网络变化。我们的中心假设是，强迫症的特征是杏仁核/腹内侧前额叶皮质与扣带回背侧(DACC)和眶前叶皮质(OFC)之间的高度连接，而dACC/OFC与背外侧和腹外侧额叶皮质之间的连接减少。这种情绪和认知控制系统之间的平衡变化导致背侧纹状体的活动状态增强。我们还假设，活动中心异常的结构基础是特定的皮质区域(或节点)，这些区域(或节点)连接情绪相关区域和参与认知控制的区域。此外，我们预测这些节点的位置在不同个体之间的可变性。最后，我们假设电路的调制将使连接配置文件恢复到相对正常的水平。这些研究将为探索新的治疗靶点提供翻译链接。由于这个网络已经与包括抑郁症、创伤后应激障碍、成瘾在内的广泛的精神障碍联系在一起，由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.