Department of Psychology, University of Bonn, Kaiser-Karl-Ring 9, 53111 Bonn, Germany.
Department of Anesthesiology, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany.
Behav Brain Res. 2022 Jul 26;430:113925. doi: 10.1016/j.bbr.2022.113925. Epub 2022 May 14.
Recent advances in the neuropsychopharmacology of metacognition indicate a constituent role of glutamate for the integrity of metamnestic processes. However, the extent to which previous results can be generalized across functional domains to characterize the relationship between glutamate and metacognition remains unclear. Here, in a randomized, double-blind, placebo-controlled, preregistered fMRI study, we tested the effects of a psychotomimetic dose (target plasma concentration 100 ng/mL) of the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist ketamine on metacognition in a perceptual decision-making framework. We collected trial-by-trial metacognitive reports as participants performed a two-alternative forced-choice perceptual task during functional magnetic resonance imaging (fMRI). Results indicated ketamine-induced deterioration in metacognitive performance, whereas no significant effects were observed for perceptual performance, response times and - unexpectedly - metacognitive bias. Whilst there were no detectable ketamine effects on mean BOLD activation, exploratory psychophysiological interaction (PPI) analysis revealed alterations in functional connectivity during metacognitive confidence ratings under ketamine. Specifically, there was increased task-specific connectivity for ketamine compared to placebo between right anterior dorsolateral prefrontal cortex and left middle temporal, supramarginal and precentral gyrus, as well as between right insula/inferior frontal gyrus and left lingual gyrus, possibly indicating re-representations of object-level features supplied for metacognitive evaluations. Overall, these findings contribute towards the emerging picture of the substructures underlying metacognitive operations at the neurotransmitter level and may shed light on a neural pattern characteristic of pharmacologically challenged metacognition.
最近在认知神经精神药理学方面的进展表明，谷氨酸对于记忆过程的完整性起着构成性作用。然而，以前的结果在多大程度上可以跨功能领域推广，以描述谷氨酸和元认知之间的关系，目前还不清楚。在这里，在一项随机、双盲、安慰剂对照、预先注册的 fMRI 研究中，我们测试了致幻剂量（目标血浆浓度 100ng/ml）的 N-甲基-D-天冬氨酸（NMDA）谷氨酸受体拮抗剂氯胺酮对知觉决策框架中元认知的影响。我们在功能磁共振成像（fMRI）期间收集了参与者执行二选一强制选择知觉任务时的逐试元认知报告。结果表明，氯胺酮导致元认知表现恶化，而对知觉表现、反应时间和——出人意料的是——元认知偏差没有显著影响。虽然在平均 BOLD 激活方面没有检测到氯胺酮的影响，但探索性的心理生理交互（PPI）分析显示，在氯胺酮下进行元认知信心评分时，功能连接发生了变化。具体来说，与安慰剂相比，氯胺酮组右额前背外侧前额叶皮层和左颞中、顶下和中央前回之间以及右岛叶/额下回和左舌回之间的任务特异性连接增加，这可能表明对象水平特征的重新表示为元认知评估提供了信息。总的来说，这些发现有助于在神经递质水平上形成元认知操作的亚结构的新兴图景，并可能为药理学挑战的元认知的神经模式提供线索。
