文章基本信息

标题：NMDA receptor function in large-scale anticorrelated neural systems with implications for cognition and schizophrenia
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作者：Alan Anticevic ; Mark Gancsos ; John D. Murray 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2012
卷号：109
期号：41
页码：16720-16725
DOI：10.1073/pnas.1208494109
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Glutamatergic neurotransmission mediated by N-methyl-D-aspartate (NMDA) receptors is vital for the cortical computations underlying cognition and might be disrupted in severe neuropsychiatric illnesses such as schizophrenia. Studies on this topic have been limited to processes in local circuits; however, cognition involves large-scale brain systems with multiple interacting regions. A prominent feature of the human brain's global architecture is the anticorrelation of default-mode vs. task-positive systems. Here, we show that administration of an NMDA glutamate receptor antagonist, ketamine, disrupted the reciprocal relationship between these systems in terms of task-dependent activation and connectivity during performance of delayed working memory. Furthermore, the degree of this disruption predicted task performance and transiently evoked symptoms characteristic of schizophrenia. We offer a parsimonious hypothesis for this disruption via biophysically realistic computational modeling, namely cortical disinhibition. Together, the present findings establish links between glutamate's role in the organization of large-scale anticorrelated neural systems, cognition, and symptoms associated with schizophrenia in humans.
关键词：default-mode network ; task-based activation ; task-based deactivation ; pharmacological manipulation ; fMRI