Only little research has been conducted on the pharmacological underpinnings of metacognition. Here, we tested the modulatory effects of a single intravenous dose (100 ng/ml) of the N-methyl-D-aspartate-glutamate-receptor antagonist ketamine, a compound known to induce altered states of consciousness, on metacognition and its neural correlates. Fifty-three young, healthy adults completed two study phases of an episodic memory task involving both encoding and retrieval in a double-blind, placebo-controlled fMRI study. Trial-by-trial confidence ratings were collected during retrieval. Effects on the subjective state of consciousness were assessed using the 5D-ASC questionnaire. Confirming that the drug elicited a psychedelic state, there were effects of ketamine on all 5D-ASC scales. Acute ketamine administration during retrieval had deleterious effects on metacognitive sensitivity (meta-d′) and led to larger metacognitive bias, with retrieval performance (d′) and reaction times remaining unaffected. However, there was no ketamine effect on metacognitive efficiency (meta-d′/d′). Measures of the BOLD signal revealed that ketamine compared to placebo elicited higher activation of posterior cortical brain areas, including superior and inferior parietal lobe, calcarine gyrus, and lingual gyrus, albeit not specific to metacognitive confidence ratings. Ketamine administered during encoding did not significantly affect performance or brain activation. Overall, our findings suggest that ketamine impacts metacognition, leading to significantly larger metacognitive bias and deterioration of metacognitive sensitivity as well as unspecific activation increases in posterior hot zone areas of the neural correlates of consciousness.

中文翻译：

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氯胺酮对情景记忆元认知过程中脑功能的影响

关于元认知的药理学基础的研究很少。在这里，我们测试了单次静脉注射剂量 (100 ng/ml) N-甲基-D-天冬氨酸-谷氨酸受体拮抗剂氯胺酮（一种已知可诱导意识状态改变的化合物）对元认知及其神经相关因素的调节作用。53 名年轻、健康的成年人在双盲、安慰剂对照的功能磁共振成像研究中完成了情景记忆任务的两个研究阶段，涉及编码和检索。在检索过程中收集了逐次试验的置信度评级。使用 5D-ASC 问卷评估对主观意识状态的影响。确认该药物会引起迷幻状态，氯胺酮对所有 5D-ASC 量表都有影响。检索过程中急性服用氯胺酮对元认知敏感性（meta-d'）产生有害影响，并导致更大的元认知偏差，而检索性能（d'）和反应时间不受影响。然而，氯胺酮对元认知效率（meta-d'/d'）没有影响。对 BOLD 信号的测量显示，与安慰剂相比，氯胺酮引起了后皮质大脑区域的更高激活，包括顶叶上叶和下叶、距状回和舌回，尽管不特定于元认知置信度评级。在编码过程中施用氯胺酮不会显着影响表现或大脑激活。总体而言，我们的研究结果表明，氯胺酮会影响元认知，导致显着更大的元认知偏差和元认知敏感性恶化，以及意识神经相关后热区区域的非特异性激活增加。