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Effects of ketamine on brain function during metacognition of episodic memory.

Mirko Lehmann, Claudia Neumann, Sven Wasserthal, Johannes Schultz, Achilles Delis, Peter Trautner, René Hurlemann, Ulrich Ettinger

Neuroscience of Consciousness 2021 DOI: 10.1093/nc/niaa028 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Double-blind, placebo-controlled fMRI study Peer reviewed
Sample size 53
Population Young, healthy adults
Intervention Ketamine
Dose 100 ng/ml
Topics Ketamine Esketamine
Keywords Confidence Episodic memory Glutamate Metacognition
Key points Acute ketamine administration during retrieval impairs metacognitive sensitivity and increases metacognitive bias without affecting memory performance or reaction times.

Abstract

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.

Comparable studies

Other randomized controlled trials on ketamine, most cited first.

Study Year Design Participants
Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Healthy human subjects recruited from the community 1994 Randomized controlled trial n = 19
Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial Patients with treatment-resistant major depression experiencing a major depressive episode 2013 Randomized controlled trial n = 73
Remifentanil-induced Postoperative Hyperalgesia and Its Prevention with Small-dose Ketamine Patients undergoing major abdominal surgery 2005 Randomized controlled trial n = 75
Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder Patients with chronic PTSD related to a range of trauma exposures 2014 Randomized controlled trial n = 41
Ketamine-Induced Deficits in Auditory and Visual Context-Dependent Processing in Healthy Volunteers Healthy volunteers 2000 Single-blind placebo-controlled study n = 20

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Ketamine Esketamine Altered states of consciousness Philosophy of mind