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A Meta-Analysis of fMRI Activation Studies of Ketamine in Healthy Participants

Published online by Cambridge University Press:  27 August 2024

J. H. Shepherd ,
A. Hickman ,
C. Baten ,
A. M. Klassen ,
G. Zamora ,
E. Johnson-Venegas ,
S. S. Madugula ,
E. Woo ,
J. A. Miller  and
M. D. Sacchet
...Show all authors
J. H. Shepherd*
Affiliation:
1Department of Psychology, California State University, Fresno, Fresno
A. Hickman
Affiliation:
1Department of Psychology, California State University, Fresno, Fresno
C. Baten
Affiliation:
1Department of Psychology, California State University, Fresno, Fresno
A. M. Klassen
Affiliation:
1Department of Psychology, California State University, Fresno, Fresno
G. Zamora
Affiliation:
1Department of Psychology, California State University, Fresno, Fresno
E. Johnson-Venegas
Affiliation:
1Department of Psychology, California State University, Fresno, Fresno
S. S. Madugula
Affiliation:
2School of Medicine, Stanford University, Stanford
E. Woo
Affiliation:
1Department of Psychology, California State University, Fresno, Fresno
J. A. Miller
Affiliation:
3Department of Psychology, Palo Alto University, Palo Alto
M. D. Sacchet
Affiliation:
4Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston
D. W. Hedges
Affiliation:
5Department of Psychology, Brigham Young University, Provo, Provo, United States
C. H. Miller
Affiliation:
1Department of Psychology, California State University, Fresno, Fresno
*
*Corresponding author.

Abstract

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Introduction

There has been rapidly growing interest in understanding the pharmaceutical and clinical properties of psychedelic and dissociative drugs, with a particular focus on ketamine. This compound, long known for its anesthetic and dissociative properties, has garnered attention due to its potential to rapidly alleviate symptoms of depression, especially in individuals with treatment-resistant depression (TRD) or acute suicidal ideation or behavior. However, while ketamine’s psychopharmacological effects are increasingly well-documented, the specific patterns of its neural impact remain a subject of exploration and basic questions remain about its effects on functional activation in both clinical and healthy populations.

Objectives

This meta-analysis seeks to contribute to the evolving landscape of neuroscience research on dissociative drugs such as ketamine by comprehensively examining the effects of acute ketamine administration on neural activation, as measured by functional magnetic resonance imaging (fMRI), in healthy participants.

Methods

We conducted a meta-analysis of existing fMRI activation studies of ketamine using multilevel kernel density analysis (MKDA). Following a comprehensive PubMed search, we quantitatively synthesized all published primary fMRI whole-brain activation studies of the effects of ketamine in healthy subjects with no overlapping samples (N=18). This approach also incorporated ensemble thresholding (α=0.05-0.0001) to minimize cluster-size detection bias and Monte Carlo simulations to correct for multiple comparisons.

Results

Our meta-analysis revealed statistically significant (p<0.05-0.0001; FWE-corrected) alterations in neural activation in multiple cortical and subcortical regions following the administration of ketamine to healthy participants (N=306).

Conclusions

These results offer valuable insights into the functional neuroanatomical effects caused by acute ketamine administration. These findings may also inform development of therapeutic applications of ketamine for various psychiatric and neurological conditions. Future studies should investigate the neural effects of ketamine administration, including both short-term and long-term effects, in clinical populations and their relation to clinical and functional improvements.

Disclosure of Interest

None Declared

Type
Abstract
Information
European Psychiatry , Volume 67 , Special Issue S1: Abstracts of the 32nd European Congress of Psychiatry , April 2024 , pp. S74
Creative Commons
Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Copyright
© The Author(s), 2024. Published by Cambridge University Press on behalf of European Psychiatric Association
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