Cognitive control is engaged by working memory processes and high-demand situations like antisaccade, where one must suppress a prepotent response. While it is known to be supported by the frontoparietal control network, how intra- and inter-areal dynamics contribute to cognitive control processes remain unclear. N-Methyl-D-aspartate glutamate receptors (NMDARs) play a key role in prefrontal dynamics that support cognitive control, and its antagonists, such as ketamine, are known to alter task-related prefrontal activities and impair cognitive performance. However, the role of NMDAR in cognitive control-related frontoparietal dynamics remain underexplored. Here, we simultaneously recorded local field potentials and single unit activities from lateral prefrontal (lPFC) and posterior parietal cortices (PPC) in two male macaque monkeys during a rule-based antisaccade task, with both Rule-Visible (RV) and Rule-Memorized (RM) conditions. In addition to altering the E/I balance in both areas, ketamine had a negative impact on rule-coding in true oscillatory activities. It also reduced frontoparietal coherence in a frequency- and rule-dependent manner. Granger prediction analysis revealed that ketamine induced an overall reduction in bidirectional connectivity. Among antisaccade trials, a greater reduction in lPFC-PPC connectivity during the delay period preceded a greater delay in saccadic onset under the RM condition, and a greater deficit in performance under the RV condition. Lastly, ketamine compromised rule coding in lPFC neurons in both RV and RM conditions, and in PPC neurons only in the RV condition. Our findings demonstrate the utility of acute NMDA receptor antagonist in understanding the mechanisms through which frontoparietal dynamics support cognitive control processes.Significance statement A low dose of ketamine is known to induce a transient cognitive control deficit in healthy humans and animals, but it remains unclear whether this deficit is related to a frontoparietal dysconnection. In macaque monkeys performing a rule-based pro- and anti-saccade task, we found that ketamine impaired information coding in frontoparietal neuron, local oscillations and inter-areal synchrony in a rule- and frequency-dependent manner. Notably, under the antisaccade rule, the amount of impairment in task performance could be predicted by the loss in fronto-parietal connectivity in the period just before the monkeys responded. The observations support the utility of NMDA receptor antagonists like ketamine as a tool to understand the role of frontoparietal dynamics in cognitive control.

中文翻译：

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氯胺酮对猕猴基于规则的扫视任务中额顶肌相互作用的影响。


认知控制由工作记忆过程和高要求情况（如反扫视）参与，在这些情况下，必须抑制前效反应。虽然已知它得到额顶叶控制网络的支持，但区域内和区域间动力学如何促进认知控制过程仍不清楚。N-甲基-D-天冬氨酸谷氨酸受体 （NMDAR） 在支持认知控制的前额叶动力学中起关键作用，其拮抗剂（如氯胺酮）已知会改变与任务相关的前额叶活动并损害认知能力。然而，NMDAR 在认知控制相关的额顶叶动力学中的作用仍未得到充分探索。在这里，我们同时记录了两只雄性猕猴在基于规则的扫视任务期间来自外侧前额叶 （lPFC） 和后顶叶皮层 （PPC） 的局部场电位和单单位活动，同时具有规则可见 （RV） 和规则记忆 （RM） 条件。除了改变这两个区域的 E/I 平衡外，氯胺酮还对真实振荡活动中的规则编码产生了负面影响。它还以频率和规则依赖的方式降低了额顶相干性。Granger 预测分析显示，氯胺酮诱导双向连接的整体减少。在抗扫视试验中，在 RM 条件下，延迟期间 lPFC-PPC 连接的减少幅度更大，扫视发作延迟幅度更大，在 RV 条件下性能缺陷更大。最后，氯胺酮在 RV 和 RM 条件下都损害了 lPFC 神经元中的规则编码，并且仅在 RV 条件下损害了 PPC 神经元的规则编码。 我们的研究结果表明，急性 NMDA 受体拮抗剂在理解额顶叶动力学支持认知控制过程的机制方面的效用。意义陈述已知低剂量的氯胺酮会在健康的人类和动物中诱导短暂的认知控制缺陷，但目前尚不清楚这种缺陷是否与额顶叶连接障碍有关。在执行基于规则的促扫视和抗扫视任务的猕猴中，我们发现氯胺酮以规则和频率依赖性方式损害额顶叶神经元的信息编码、局部振荡和区域间同步。值得注意的是，在反扫视规则下，任务表现的损害程度可以通过猴子反应前额顶叶连接的丧失来预测。这些观察结果支持氯胺酮等 NMDA 受体拮抗剂作为了解额顶叶动力学在认知控制中的作用的工具的效用。