Neurocircuitry Underlying DBS Effects in OCD: A Window Into Mechanisms of Action

描述(申请人提供)：该中心的总体目标是描绘作为强迫症核心行为特征基础的神经网络，以扩大我们对疾病的理解以及持续高频刺激(DBS)对这些神经网络的影响。一种驱动假说是，强迫症症状的部分原因是恐惧的消退受损，干扰了回避和寻求奖励之间的正常平衡。作为回避行为基础的神经网络，包括前额叶皮质、腹侧纹状体和杏仁核区域，与支撑寻求奖励行为的一般回路是相同的。这个环路(前扣带回/眶-基底节连接)的功能障碍与强迫症密切相关。我们的目标是提高我们对强迫症相关行为背后的神经网络的理解，这将通过一系列综合的翻译实验来实现，这些实验涉及腹侧内囊和腹侧纹状体对行为、功能成像、系统和细胞电生理学的高频刺激效应，以及与这种刺激相关的电路。尤其重要的是，前额-基底神经节回路的功能障碍也与情感、焦虑、冲动控制和成瘾障碍有关。总体而言，这项工作将为 不仅为强迫症设计新的治疗方法，而且还为其他精神疾病设计新的治疗方法。它的跨学科性质将扩展我们对构成特定行为(灭绝、回避和寻求奖励行为)的神经回路的基本知识。这些研究的结果也将为我们理解DBS的基本机制做出重要的新贡献。

DESCRIPTION (provided by applicant): The overall goals of this center are to delineate the neural networks that underlie core behavioral features of OCD in order to broaden our understanding of the disease and the effects of continuous high frequency stimulation (DBS) on those neural networks. A driving hypothesis is that OCD symptoms are, in part, due to impaired extinction of fear that interferes with the normal balance between avoidance and reward-seeking. The neural network that underlies avoidance behaviors, including regions of the prefrontal cortex, ventral striatum and amygdala, is the same general circuit that underlies reward-seeking behaviors. Dysfunction within this circuit, (the anterior cingulate/orbital-basal-ganglia connections), is strongly implicated in OCD. Our goal to improve our understanding of the neural network that underlies OCD-related behaviors will be accomplished through a series of integrated translational experiments that involve high frequency stimulation effects of the ventral internal capsule and ventral striatum on behavior, functional imaging, systems and cellular electrophysiology, and the circuits that are associated with this stimulation. Of particular importance is that dysfunction in the prefrontal-basal ganglia circuit is also implicated across affective, anxiety, impulse-control and addictive disorders. Collectively, this work will provide a blueprint for devising new therapies not only for OCD, but also for other psychiatric disorders. Its interdisciplinary nature will expand our basic knowledge of the neurocircuitry that underlies specific behaviors, (extinction, avoidance and reward seeking behaviors). Results from these studies will also make important new contributions to our understanding of the basic mechanisms of DBS.