Connectome harmonic decomposition tracks the presence of disconnected consciousness during ketamine-induced unresponsiveness.
Milan Van Maldegem, Jakub Vohryzek, Selen Atasoy, Naji Alnagger, Paolo Cardone, Vincent Bonhomme, Audrey Vanhaudenhuyse, Athena Demertzi, Océane Jaquet, Mohamed Ali Bahri, Pablo Núñez, Morten L. Kringelbach, Emmanuel A. Stamatakis, Andrea I. Luppi
British Journal of Anaesthesia April 1, 2025 DOI: 10.1016/j.bja.2024.12.036 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Intervention | Ketamine |
| Dose | doses suitable to induce anaesthesia in humans |
| Topics | Esketamine Ketamine |
| Keywords | Consciousness research Psychedelic medicine Brain imaging Ketamine effects Anesthesia studies Connectome harmonics Dissociative anaesthesia Functional MRI Ketamine dreams Unresponsiveness |
| Citations | 3 |
| Key findings | The connectome harmonic signature of ketamine-induced unresponsiveness aligns with psychedelic states and misaligns with unconscious states from propofol or brain injury. |
Abstract
Ketamine, in doses suitable to induce anaesthesia in humans, gives rise to a unique state of unresponsiveness accompanied by vivid experiences and sensations, making it possible to disentangle the correlated but distinct concepts of conscious awareness and behavioural responsiveness. This distinction is often overlooked in the study of consciousness. The mathematical framework of connectome harmonic decomposition (CHD) was used to view functional magnetic resonance imaging (fMRI) signals during ketamine-induced unresponsiveness as distributed patterns across spatial scales. The connectome harmonic signature of this particular state was mapped onto signatures of other states of consciousness for comparison. An increased prevalence of fine-grained connectome harmonics was found in fMRI signals obtained during ketamine-induced unresponsiveness, indicating higher granularity. After statistical assessment, the ketamine sedation harmonic signature showed alignment with signatures of LSD-induced (fixed effect =0.0113 [0.0099, 0.0127], P<0.001) or ketamine-induced (fixed effect =0.0087 [0.0071, 0.0103], P<0.001) psychedelic states, and misalignment with signatures seen in unconscious individuals owing to propofol sedation (fixed effect =-0.0213 [-0.0245, -0.0181], P<0.001) or brain injury (fixed effect =-0.0205 [-0.0234, -0.0178], P<0.001). The CHD framework, which only requires resting-state fMRI data and can be applied retrospectively, has the ability to track alterations in conscious awareness in the absence of behavioural responsiveness on a group level. This is possible because of ketamine's unique property of decoupling these two facets, and is important for consciousness and anaesthesia research.
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 4
- Illuminating brain's "dark energy": a living lens of spontaneous slow oscillations. reply to comments on 'dark brain energy: toward an integrative model of spontaneous slow oscillations'. Physics of Life Reviews January 21, 2026
- Psilocybin shapes the slow, global propagation of brain activity over the cortical layout of 5HT2a receptors Communications Biology March 26, 2026
- 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
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- Detecting Awareness in the Vegetative State Science September 7, 2006
- A Theoretically Based Index of Consciousness Independent of Sensory Processing and Behavior Science Translational Medicine August 14, 2013
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- Psychometric Evaluation of the Altered States of Consciousness Rating Scale (OAV) PLoS One August 31, 2010
and 53 more in the library