General Anesthesia and Discrete Components of Ketamine Neurophysiology
Ben Deverett1, Duan Li2, Theresa R Lii1
1Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, California.
JAMA Psychiatry
|April 8, 2026
Summary
General anesthesia (GA) selectively alters ketamine's neurophysiologic effects, preserving beta-gamma power but diminishing theta augmentation. This finding offers a new approach to understanding ketamine's therapeutic mechanisms.
Area of Science:
- Neuroscience
- Pharmacology
- Anesthesiology
Background:
- Ketamine exhibits dissociative, analgesic, and antidepressant properties.
- Neurophysiologic effects of ketamine are not fully understood regarding separate modulation.
- Cortical oscillations are linked to specific therapeutic effects, suggesting targeted modulation is possible.
Purpose of the Study:
- To investigate if general anesthesia (GA) modifies the neurophysiologic signatures of ketamine.
- To determine if ketamine's electroencephalographic (EEG) effects differ with and without GA.
- To explore selective modulation of ketamine's neurophysiologic correlates.
Main Methods:
- Secondary analysis of participant-level data from 3 prospective studies (2017-2023).
- Inclusion of healthy volunteers, surgical patients, and patients with depression (n=79).
- Administration of subanesthetic ketamine infusion (0.5 mg/kg) with or without GA; EEG band power changes measured.
Main Results:
- General anesthesia (GA) differentially altered EEG features associated with ketamine.
- Ketamine during GA preserved beta-gamma (βγ) power modulation compared to awake administration.
- Ketamine during GA failed to augment theta (θ) power, unlike during awake administration.
Conclusions:
- Coadministration of ketamine with GA selectively modulates the theta (θ) but not the beta-gamma (βγ) neurophysiologic correlates.
- Findings suggest a method to investigate the role of specific neurophysiologic components in ketamine's behavioral effects.
- Potential for developing more targeted therapies by selectively modulating ketamine's actions.
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