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A Meta-Analysis of Functional Neuroimaging Studies of Ketamine Administration in Healthy Volunteers.

Karim Ait Bentaleb, Mélanie Boisvert, Valérie Tourjman, Stéphane Potvin

Journal of Psychoactive Drugs 2024 DOI: 10.1080/02791072.2023.2190758 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Meta-analysis Peer reviewed
Intervention Ketamine
Topics Ketamine Esketamine
Keywords Executive functions Functional imaging Meta-analysis Resting-state
Key findings The authors report that ketamine administration increased resting activity in the dorsal anterior cingulate cortex and increased right Heschl's gyrus activation during executive tasks at a stringent threshold, with uncorrected increases in the right insula and right fusiform gyrus at rest and the rostral anterior cingulate during executive tasks. They argue these findings parallel alterations in schizophrenia, supporting the ketamine model of psychosis, and that rostral ACC changes may reflect failed default mode network deactivation.

Abstract

Ketamine administration leads to a psychotomimetic state when taken in large bolus doses, making it a valid model of psychosis. Therefore, understanding ketamine's effects on brain functioning is particularly relevant. This meta-analysis focused on neuroimaging studies that examined ketamine-induced brain activation at rest and during a task. Included are 10 resting-state studies and 23 task-based studies, 9 of which were measuring executive functions. Using a stringent statistical threshold (TFCE <0.05), the results showed increased activity at rest in the dorsal anterior cingulate cortex (ACC), and increased activation of the right Heschl's gyrus during executive tasks, following ketamine administration. Uncorrected results showed increased activation at rest in the right (anterior) insula and the right-fusiform gyrus, as well as increased activation during executive tasks in the rostral ACC. Rest-state studies highlighted alterations in core hubs of the salience network, while task-based studies suggested an impact on task-irrelevant brain regions. Increased activation in the rostral ACC may indicate a failure to deactivate the default mode network during executive tasks following ketamine administration. The results are coherent with alterations found in schizophrenia, which confer external validity to the ketamine model of psychosis. Studies investigating the neural mechanisms of ketamine's antidepressant action are warranted.

Comparable studies

Other systematic reviews and meta-analyses on ketamine, most cited first.

Study Year Design Participants
The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis Depressed patients with suicidal ideation at baseline 2017 Systematic review and individual participant data meta-analysis n = 167
Ketamine use: a review Ketamine users 2011 Systematic review
Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression Participants with major depression in placebo-controlled, double-blind, randomized... 2015 Systematic review and meta-analysis
Ketamine and postoperative pain – a quantitative systematic review of randomised trials Surgical patients from 25 countries 2004 Systematic review n = 2,839
Side-effects associated with ketamine use in depression: a systematic review. Patients with depression 2018 Systematic review

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