The Function and role of Basal Ganglia pathways: From single to multiple loops

基底神经节有助于通过试错学习形成的各种认知和运动功能。与皮层和丘脑一起，它们建立了一个平行但相互作用的环路结构。在现有的皮质-基底神经节-丘脑-皮质处理计算模型预测的指导下，我们将进行电生理学实验来解决两个重要的尚未解决的经验问题：1）苍白球的外部部分如何促进基底神经节处理和2）独立的基底神经节回路如何支持运动规划和运动执行连贯地相互作用？基于我们的实证研究结果，我们将扩展计算模型，以完全捕获基底神经节内和环之间的连接。从临床的角度来看，我们随后将系统地将病变和功能改变应用于该模型，并研究它们对一组认知和运动任务中的显性模型行为的影响。同时，我们将这些相同的任务应用于基底神经节疾病的患者，这些患者的神经元病因尚不清楚（例如肌张力障碍、亨廷顿病、强迫症、图雷特综合征和原发性震颤）。这些模型的改变和病变-跨任务-再现患者的行为缺陷将提供对这些疾病背后的神经元功能障碍的见解。

Basal ganglia contribute to a variety of cognitive and motor functions which are formed through trial-and-error learning. With cortex and thalamus, they build an architecture of parallel but interacting loops. Guided by predictions of an existing computational model of cortico-basalganglio-thalamo-cortical processing, we will perform electrophysiological experiments to solve two important yet unresolved empirical questions: 1) How does the external segment of globus pallidus contribute to basal ganglia processing and 2) How do separate basal ganglia loops that support motor planning and motor execution coherently interact? Based on our empirical findings, we will then extend the computational model to fully capture basal ganglia connectivity both within and between loops. Towards a clinical perspective, we will afterwards systematically apply lesions and functional alterations to this model and study their effects on overt model behavior in a set of cognitive and motor tasks. At the same time, we will apply these same tasks to patients of basal ganglia disorders that are yet poorly understood with regard to their neuronal causes (e.g. dystonia, Huntington’s disease, Obsessive Compulsive Disorder, Tourette’s syndrome and essential tremor). Those model alterations and lesions that - across tasks - reproduce the patients’ behavioral deficits will provide insights into the neuronal dysfunctions underlying these disorders.