The Administration of Ketamine Is Associated with Dose-Dependent Stabilization of Cortical Dynamics in Humans.
Diego G Dávila, Andrew McKinstry-Wu, Max B Kelz, Alex Proekt
Journal of Neuroscience May 14, 2025 DOI: 10.1523/JNEUROSCI.1545-24.2025 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Human male volunteers |
| Intervention | Ketamine |
| Dose | escalating doses |
| Topics | Ketamine Esketamine |
| Keywords | EEG Dissociated state Dynamics Consciousness-research Psychopharmacology Brain-imaging Altered-states |
| Citations | 5 |
| Key findings | Stabilization of cortical dynamics, especially at higher frequencies, correlates with decreased ability to perceive external stimuli during ketamine-induced dissociation, rather than with the capacity for conscious experience. |
Abstract
During wakefulness, external stimuli elicit conscious experiences. In contrast, dreams and drug-induced dissociated states are characterized by vivid internally generated conscious experiences and reduced ability to perceive external stimuli. Understanding the physiological distinctions between normal wakefulness and dissociated states may therefore disambiguate signatures of responsiveness to external stimuli from those that underlie conscious experience. The hypothesis that conscious experiences are associated with brain criticality has received considerable theoretical and experimental support. Consistent with this hypothesis, statistical signatures of criticality are similar in normal wakefulness and dissociative states but are abolished in dreamless sleep and under anesthesia. Thus, while statistical measures of criticality are associated with the ability to have conscious experience, they do not readily distinguish between perception of the external world from internally generated percepts. Here, we investigate distinct, dynamical, signatures of criticality during escalating ketamine doses in high-density EEG in human male volunteers. We show that during normal wakefulness, EEG is found at a critical point between damped and exploding oscillations. With increasing doses of ketamine, as dissociative symptoms intensify, activity is progressively stabilized-most prominently at higher frequencies. We also show that stabilization is a more reliable marker of the effects of ketamine than conventional measures such as power spectra. These findings suggest that stabilization of cortical dynamics correlates with decreased ability to respond to and perceive external stimuli rather than the ability to have conscious experiences per se. Altogether, these results suggest that combining statistical and dynamical criticality measures may distinguish wakefulness, dissociation, and unconsciousness.
Comparable studies
Other experimental studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Ketamine activates psychosis and alters limbic blood flow in schizophrenia Schizophrenic individuals | 1995 | Experimental study | |
| The spectral exponent of the resting EEG indexes the presence of consciousness during unresponsiveness induced by propofol, xenon, and ketamine Healthy participants | 2019 | Controlled experimental study | n = 15 |
| Ketamine Increases Human Motor Cortex Excitability to Transcranial Magnetic Stimulation Normal human subjects | 2003 | Experimental study | n = 7 |
| Evidence that Subanesthetic Doses of Ketamine Cause Sustained Disruptions of NMDA and AMPA-Mediated Frontoparietal Connectivity in Humans Human participants | 2015 | Experimental study | |
| Simultaneous population pharmacokinetic modelling of ketamine and three major metabolites in patients with treatment‐resistant bipolar depression Patients with treatment-resistant bipolar depression | 2012 | Population pharmacokinetic analysis | n = 9 |
Citations in the library
Cited by 4
- Rapid antidepressant potential of nitrous oxide: current state and major questions. Molecular Psychiatry June 1, 2026
- Cortical Mechanisms Contributing to Ketamine-Induced Dissociation The Neuroscientist December 26, 2025
- 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
Cites 5
- Deep posteromedial cortical rhythm in dissociation Nature September 16, 2020
- Consciousness is supported by near-critical slow cortical electrodynamics. Proceedings of the National Academy of Sciences February 1, 2022
- Subanaesthetic ketamine and altered states of consciousness in humans British Journal of Anaesthesia April 13, 2018
- Characterizing brain dynamics during ketamine-induced dissociation and subsequent interactions with propofol using human intracranial neurophysiology Nature Communications March 29, 2023
- Acute psychoactive effects of intravenous ketamine during treatment of mood disorders: Analysis of the Clinician Administered Dissociative State Scale. Journal of Affective Disorders February 2018