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

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.

KEYWORDS:

• Ketamine
• meta-analysis
• functional imaging
• resting-state
• executive functions

Acknowledgments

SP is holder of the Eli Lilly Canada Chair on schizophrenia research. MB is holder of a master’s scholarship from the Fonds de Recherche du Québec en Santé.

Disclosure statement

No potential conflict of interest was reported by the authors.

Author contribution

SP designed the study; KAB and MB did the literature search; KAB and MB did data extraction; KAB and SP performed the analyses; KAB and SP wrote the manuscript; MB and VT provided critical comments; All authors approved the final version of the manuscript.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/02791072.2023.2190758.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.