N-methyl-d-aspartate Receptor Antagonist Ketamine Impairs Action-monitoring Activity in the Prefrontal Cortex
N-methyl-d-aspartate Receptor Antagonist Ketamine Impairs Action-monitoring Activity in the Prefrontal Cortex
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DOI：
10.1162/jocn_a_00519
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发表时间：
2014-03
影响因子：
3.2
通讯作者：
K. Skoblenick;S. Everling
中科院分区：
文献类型：
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作者：
K. Skoblenick;S. Everling
自我产生的行为监测失败被认为是精神分裂症阳性症状的基础。据推测，这些缺陷可能是由N-甲基-d-天冬氨酸受体（NMDAR）功能障碍引起的。在这里，我们记录了前额叶神经元的活动在猴子执行一个antisaccade任务，而我们管理的非竞争性NMDAR拮抗剂氯胺酮亚麻醉剂量。许多神经元区分正确的antisaccades和反应错误，在他们的postresponse活动。氯胺酮增加神经元的非偏好反应的活性，从而降低神经元的性能选择性。氯胺酮也影响了猴子在错误后的行为，这与错误检测的缺陷一致。结果表明，NMDAR在灵长类动物的行为监测中起着重要作用。氯胺酮后前额叶神经元的性能选择性的降低可以帮助解释氯胺酮给药后在人类中发现的动作监测缺陷，并为以下假设提供支持：NMDAR功能障碍是精神分裂症中自我监测缺陷和精神病性症状的基础。
Failures in monitoring of self-generated actions are thought to underlie the positive symptoms in schizophrenia. It has been hypothesized that these deficits may be caused by a dysfunction of N-methyl-d-aspartate receptors (NMDARs). Here we recorded the activity of prefrontal neurons in monkeys performing an antisaccade task, while we administered a subanesthetic dose of the noncompetitive NMDAR antagonist ketamine. Many neurons discriminated between correct antisaccades and response errors in their postresponse activity. Ketamine increased the activity for the neurons' nonpreferred response, thereby decreasing the neurons' performance selectivity. Ketamine also affected the monkeys' behavior after an error, consistent with a deficit in error detection. The results show that NMDARs play an important role in action monitoring in primates. The decrease in performance selectivity of prefrontal neurons after ketamine can help to explain the deficits in action monitoring found in humans after ketamine administration and provides support for the hypothesis that an NMDAR dysfunction underlies self-monitoring deficits and psychotic symptoms in schizophrenia.