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基底神经节-小脑-丘脑-皮质系统功能障碍会导致抽动秽语综合征中的运动性抽动。

Dysfunctions of the basal ganglia-cerebellar-thalamo-cortical system produce motor tics in Tourette syndrome.

作者信息

Caligiore Daniele, Mannella Francesco, Arbib Michael A, Baldassarre Gianluca

机构信息

Laboratory of Computational Embodied Neuroscience, Institute of Cognitive Sciences and Technologies, National Research Council (CNR-ISTC-LOCEN), Roma, Italy.

Neuroscience Program, USC Brain Project, Computer Science Department, University of Southern California, Los Angeles, California, United States of America.

出版信息

PLoS Comput Biol. 2017 Mar 30;13(3):e1005395. doi: 10.1371/journal.pcbi.1005395. eCollection 2017 Mar.

Abstract

Motor tics are a cardinal feature of Tourette syndrome and are traditionally associated with an excess of striatal dopamine in the basal ganglia. Recent evidence increasingly supports a more articulated view where cerebellum and cortex, working closely in concert with basal ganglia, are also involved in tic production. Building on such evidence, this article proposes a computational model of the basal ganglia-cerebellar-thalamo-cortical system to study how motor tics are generated in Tourette syndrome. In particular, the model: (i) reproduces the main results of recent experiments about the involvement of the basal ganglia-cerebellar-thalamo-cortical system in tic generation; (ii) suggests an explanation of the system-level mechanisms underlying motor tic production: in this respect, the model predicts that the interplay between dopaminergic signal and cortical activity contributes to triggering the tic event and that the recently discovered basal ganglia-cerebellar anatomical pathway may support the involvement of the cerebellum in tic production; (iii) furnishes predictions on the amount of tics generated when striatal dopamine increases and when the cortex is externally stimulated. These predictions could be important in identifying new brain target areas for future therapies. Finally, the model represents the first computational attempt to study the role of the recently discovered basal ganglia-cerebellar anatomical links. Studying this non-cortex-mediated basal ganglia-cerebellar interaction could radically change our perspective about how these areas interact with each other and with the cortex. Overall, the model also shows the utility of casting Tourette syndrome within a system-level perspective rather than viewing it as related to the dysfunction of a single brain area.

摘要

运动性抽动是妥瑞氏综合征的主要特征,传统上与基底神经节中纹状体多巴胺过多有关。最近的证据越来越支持一种更清晰的观点,即小脑和皮层与基底神经节密切协同工作,也参与抽动的产生。基于这些证据,本文提出了一个基底神经节 - 小脑 - 丘脑 - 皮层系统的计算模型,以研究妥瑞氏综合征中运动性抽动是如何产生的。具体而言,该模型:(i)再现了最近关于基底神经节 - 小脑 - 丘脑 - 皮层系统参与抽动产生的实验的主要结果;(ii)提出了对运动性抽动产生的系统层面机制的一种解释:在这方面,该模型预测多巴胺能信号与皮层活动之间的相互作用有助于触发抽动事件,并且最近发现的基底神经节 - 小脑解剖通路可能支持小脑参与抽动的产生;(iii)提供了关于纹状体多巴胺增加以及皮层受到外部刺激时产生的抽动数量的预测。这些预测对于确定未来治疗的新脑靶点区域可能很重要。最后,该模型代表了首次研究最近发现的基底神经节 - 小脑解剖联系作用的计算尝试。研究这种非皮层介导的基底神经节 - 小脑相互作用可能会从根本上改变我们对这些区域如何相互作用以及与皮层相互作用的看法。总体而言,该模型还展示了从系统层面的角度看待妥瑞氏综合征的实用性,而不是将其视为与单个脑区功能障碍相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b3f/5373520/f5c41d26c888/pcbi.1005395.g001.jpg

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