General Anesthesia and Discrete Components of Ketamine Neurophysiology.
Ben Deverett, Duan Li, Theresa R. Lii, Phillip E. Vlisides, Vijay Tarnal, Anna Forsyth, Rachael Sumner, Pilleriin Sikka, Alan F. Schatzberg, Suresh Muthukumaraswamy, George A. Mashour, Boris D. Heifets
JAMA Psychiatry June 1, 2026 DOI: 10.1001/jamapsychiatry.2026.0190 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Cohort study Peer reviewed |
|---|---|
| Sample size | 52 |
| Population | Healthy volunteers, patients undergoing elective surgery, and patients with depression (aged ≥18 years) |
| Interventions | Ketamine General anesthesia |
| Dose | 0.5 mg/kg body weight |
| Duration | 40-minute infusion |
| Topics | Esketamine Ketamine |
| Citations | 1 |
| Key findings | General anesthesia selectively blocked ketamine's theta oscillations while preserving its beta-gamma oscillations. |
Abstract
Ketamine has well-known dissociative, analgesic, and antidepressant properties, but it is unknown whether the neurophysiologic effects that are associated with these properties can be modulated separately from one another. Considering that specific cortical oscillations have been associated with specific therapeutic effects, modulating selective aspects of ketamine neurophysiology could inform efforts to develop more targeted therapies. To determine whether the neurophysiologic signatures of ketamine are associated with removal of conscious awareness using general anesthesia (GA). This cohort study was a secondary analysis of participant-level data from 3 prospective studies conducted between 2017 and 2023. The primary analysis included data from 2 study cohorts (University of Michigan and Stanford University), and the supplementary analysis included data from a third cohort (University of Auckland). The study cohorts included healthy volunteers, patients undergoing elective surgery, and patients with a diagnosis of depression (all aged ≥18 years). Participants received a subanesthetic infusion of ketamine (0.5 mg/kg body weight) over 40 minutes or placebo with or without GA. The primary outcome was change in electroencephalographic (EEG) band power during medication infusion. Changes were computed using nonparametric paired statistical text (Wilcoxon signed-rank test). This study included 52 participants in the primary analysis (mean [SD] age, 43.4 [18.3] years; 34 females [65.4%]) and 27 additional participants in the supplementary analysis (mean [SD] age, 30.2 [8.2] years; 15 females [55.6%]). GA differentially altered EEG features commonly associated with ketamine in all 52 participants (100%) in the primary analysis. Compared with awake administration, ketamine administered during GA preserved its βγ power modulation (mean [SEM] increase from 6.3 [11.3] to 11.6 [2.2] dB for awake administration; increase from 8.5 [2.9] to 11.2 [3.8] dB for administration during GA) but lacked its characteristic θ augmentation (increase from 17.3 [10.5] to 22.9 [3.1] dB during awake administration; nonsignificant decrease from 29.0 [3.0] to 27.8 [3.5] dB for administration during GA). In this cohort study, coadministration of ketamine with GA selectively modulated the θ but not the βγ neurophysiologic correlates of ketamine. These findings suggest a potential method to explore the role of these components in the behavioral effects of ketamine.
Comparable studies
Other observational and cohort studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Taming the Ketamine Tiger Volunteers from a prison population | 2010 | Observational study | n = 20 |
| Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin Humans | 2017 | Observational study | |
| Disruption of Frontal–Parietal Communication by Ketamine, Propofol, and Sevoflurane Surgical patients undergoing induction of anesthesia with intravenous ketamine | 2013 | Observational cohort | n = 30 |
| Do the dissociative side effects of ketamine mediate its antidepressant effects? Treatment-resistant inpatients with major depressive disorder or bipolar disorder | 2014 | Observational cohort | n = 108 |
| Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder Patients with treatment-resistant major depressive disorder | 2012 | Observational cohort | n = 30 |
Citations in the library
Cited by 3
- Cellular and Microcircuit Mechanisms of Anesthetic Disruption of Conscious-State Organization. Cells August 18, 2026
- Ketamine Across the Dose-State Continuum: EEG Signatures, Network Dynamics, and Implications for Brain-State Monitoring in Anesthesia and Critical Care. Brain Sciences August 9, 2026
- Protocol and pilot results for a double-blind randomized placebo-controlled trial of ketamine under propofol sedation for chronic pain and depression. Pain Management April 16, 2026
Cites 11
- Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Journal of Neuroscience April 15, 1997
- Ketamine: 50 Years of Modulating the Mind Frontiers in Human Neuroscience November 29, 2016
- Deep posteromedial cortical rhythm in dissociation Nature September 16, 2020
- Evidence that Subanesthetic Doses of Ketamine Cause Sustained Disruptions of NMDA and AMPA-Mediated Frontoparietal Connectivity in Humans Journal of Neuroscience August 19, 2015
- Cortical dynamics during psychedelic and anesthetized states induced by ketamine Neuroimage April 5, 2019
and 6 more in the library