CRCNS US-German-Israeli Research Proposal: Multi-Level Neuro-Computational Models of Basal Ganglia Dysfunction in Tourette Syndrome

图雷特综合症是一种神经系统疾病，其特征是突然运动和发声，称为抽搐。这种疾病会使人非常虚弱，并产生严重的临床和社会影响。这项工作的总体目标是结合实验和计算方法，以更好地了解导致tic生产的机制。在过去的研究中，抽动症的产生与多种大脑区域的异常活动有关，其中许多区域位于基底神经节。动物实验表明，阻断基底神经节神经元之间某些形式的信号传导会诱发抽搐。该项目将采用创新的方法从这些产生tic的动物模型的基底神经节神经元中收集数据，这些数据将用于多种方式。数据分析将确定与抽动产生相关的神经活动的变化，提供有关神经元相互作用的详细视图。这些数据还将指导两个新的计算模型网络的发展，一个是集中的，一个是大规模的。这些模型将用于探索基底神经节内神经元之间的信号变化，以及基底神经节与皮层主要运动指挥中心之间的信号变化如何导致抽动产生。这些计算研究的结果将为随后的实验测试提供预测。要执行一个动作，必须从无数可能的动作中进行选择。这个动作选择是如何完成的，目前还不是很清楚。该项目将增强我们对神经元活动和信号的变化如何导致抽动产生以及一般行为选择的理解。抽动产生的结果将通过提出干预目标和提供测试潜在治疗效果的框架，对图雷特综合征具有临床意义。目前，在图雷特综合征领域缺乏这样的框架，相关的计算研究也相当有限。所开发的模型还将通过为研究与神经元活动和与运动相关的大脑区域的神经元之间的信号传导有关的其他问题提供资源，推动该领域的发展。伙伴项目由德国联邦教育和研究部（BMBF）和美国-以色列两国科学基金会（BSF）资助。

Tourette syndrome is a neurological disorder characterized by sudden movements and vocalizations known as tics. The disorder can be highly debilitating with severe clinical and social effects. The overall goal of this work is to combine experimental and computational approaches to better understand the mechanisms leading to tic production. In past work, tic production has been linked to abnormal activity in a variety of brain regions, many of which are in an area called the basal ganglia. Experiments in animals have shown that blocking certain forms of signaling between neurons in the basal ganglia induces tics. This project will use innovative methods to collect data from neurons in the basal ganglia in these tic-producing animal models, which will be used in several ways. Data analysis will identify changes in neural activity that are linked with tic production, providing a detailed view of the neuronal interactions involved. The data will also guide the development of two novel computational model networks, one focused and one large-scale. These models will be used to explore how changes in signaling between neurons within the basal ganglia, as well as between the basal ganglia and major motor command centers in the cortex, can lead to tic production. Results of these computational studies will yield predictions for subsequent experimental testing. For an action to be performed, it must be selected from among the myriad of possible movements that could be made. How this action selection is accomplished is currently not well understood. This project will enhance our understanding of how changes in neuronal activity and signaling lead to tic production, as well as to the selection of actions in general. The results about tic production will have clinical implications for Tourette syndrome by suggesting targets for interventions and providing a framework for testing the impact of potential treatments. Currently, such a framework in the area of Tourette syndrome is lacking, and related computational studies have been quite limited. The models developed will also advance the field by serving as resources for the study of additional questions relating to neuronal activity and to signaling between neurons in movement-related brain areas. Companion projects are being funded by the Federal Ministry of Education and Research, Germany (BMBF), and the US-Israel Binational Science Foundation (BSF).