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。通过皮质和丘脑，它们构建了一个并行但相互作用的循环结构。在现有皮质-基底神经节-丘脑-皮质处理计算模型预测的指导下，我们将进行电生理实验，以解决两个重要但尚未解决的经验问题：1)苍白球外段如何促进基底神经节处理；2)支持运动计划和运动执行的单独基底神经节回路如何连贯地相互作用？基于我们的实证研究结果，我们将扩展计算模型，以充分捕获环内和环间的基底神经节连接。从临床角度来看，我们随后将系统地将病变和功能改变应用于该模型，并研究它们对一系列认知和运动任务中显性模型行为的影响。与此同时，我们将把这些相同的任务应用于基底神经节疾病患者，这些患者对其神经元原因知之甚少（例如肌张力障碍、亨廷顿氏病、强迫症、妥瑞氏综合征和特发性震颤）。这些模型的改变和损伤——跨越任务——重现了患者的行为缺陷，将为了解这些疾病背后的神经功能障碍提供洞见。

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.