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恒河猴连接组预测杏仁核药物遗传学失活导致的功能网络破坏。

The Rhesus Monkey Connectome Predicts Disrupted Functional Networks Resulting from Pharmacogenetic Inactivation of the Amygdala.

作者信息

Grayson David S, Bliss-Moreau Eliza, Machado Christopher J, Bennett Jeffrey, Shen Kelly, Grant Kathleen A, Fair Damien A, Amaral David G

机构信息

Department of Psychiatry and Behavioral Sciences, University of California, Davis, Sacramento, CA 95817, USA; The MIND Institute, University of California, Davis, Sacramento, CA 95817, USA; Center for Neuroscience, University of California, Davis, Davis, CA 95616, USA.

Department of Psychiatry and Behavioral Sciences, University of California, Davis, Sacramento, CA 95817, USA; California National Primate Research Center, University of California, Davis, Davis, CA 95616, USA.

出版信息

Neuron. 2016 Jul 20;91(2):453-66. doi: 10.1016/j.neuron.2016.06.005.

Abstract

Contemporary research suggests that the mammalian brain is a complex system, implying that damage to even a single functional area could have widespread consequences across the system. To test this hypothesis, we pharmacogenetically inactivated the rhesus monkey amygdala, a subcortical region with distributed and well-defined cortical connectivity. We then examined the impact of that perturbation on global network organization using resting-state functional connectivity MRI. Amygdala inactivation disrupted amygdalocortical communication and distributed corticocortical coupling across multiple functional brain systems. Altered coupling was explained using a graph-based analysis of experimentally established structural connectivity to simulate disconnection of the amygdala. Communication capacity via monosynaptic and polysynaptic pathways, in aggregate, largely accounted for the correlational structure of endogenous brain activity and many of the non-local changes that resulted from amygdala inactivation. These results highlight the structural basis of distributed neural activity and suggest a strategy for linking focal neuropathology to remote neurophysiological changes.

摘要

当代研究表明,哺乳动物的大脑是一个复杂的系统,这意味着即使对单个功能区域造成损伤,也可能在整个系统中产生广泛的后果。为了验证这一假设,我们通过药物遗传学方法使恒河猴杏仁核失活,杏仁核是一个具有分布式且明确的皮层连接的皮层下区域。然后,我们使用静息态功能连接磁共振成像来研究这种扰动对全局网络组织的影响。杏仁核失活破坏了杏仁核与皮层之间的通信,并在多个功能性脑系统中分散了皮层与皮层之间的耦合。通过基于图形的分析,利用实验建立的结构连接性来模拟杏仁核的断开连接,从而解释了耦合的变化。总的来说,通过单突触和多突触途径的通信能力在很大程度上解释了内源性脑活动的相关结构以及杏仁核失活导致的许多非局部变化。这些结果突出了分布式神经活动的结构基础,并提出了一种将局灶性神经病理学与远程神经生理变化联系起来的策略。

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