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; Oceane Jaquet; Mohamed Ali Bahri; Pablo Nunez; Morten L. Kringelbach; Emmanuel A. Stamatakis; Andrea I. Luppi

doi:10.1016/j.bja.2024.12.036

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, Oceane Jaquet, Mohamed Ali Bahri, Pablo Nunez, Morten L. Kringelbach, Emmanuel A. Stamatakis, Andrea I. Luppi

^*Corresponding author for this work

Department of Clinical Medicine - Center for Music In the Brain

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

Abstract

Background: 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. Methods: 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. Results: 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). Conclusions: 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.

Original language	English
Journal	British Journal of Anaesthesia
Volume	134
Issue	4
Pages (from-to)	1088-1104
Number of pages	17
ISSN	0007-0912
DOIs	https://doi.org/10.1016/j.bja.2024.12.036
Publication status	Published - Apr 2025

Keywords

connectome harmonics
consciousness
dissociative anaesthesia
functional MRI
ketamine dreams
unresponsiveness

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10.1016/j.bja.2024.12.036Licence: CC BY

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Van Maldegem, M., Vohryzek, J., Atasoy, S., Alnagger, N., Cardone, P., Bonhomme, V., Vanhaudenhuyse, A., Demertzi, A., Jaquet, O., Bahri, M. A., Nunez, P., Kringelbach, M. L., Stamatakis, E. A., & Luppi, A. I. (2025). Connectome harmonic decomposition tracks the presence of disconnected consciousness during ketamine-induced unresponsiveness. British Journal of Anaesthesia, 134(4), 1088-1104. https://doi.org/10.1016/j.bja.2024.12.036

@article{1a94f2bc0efb44fb9c319b673c0f9622,

title = "Connectome harmonic decomposition tracks the presence of disconnected consciousness during ketamine-induced unresponsiveness",

abstract = "Background: 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. Methods: 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. Results: 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). Conclusions: 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.",

keywords = "connectome harmonics, consciousness, dissociative anaesthesia, functional MRI, ketamine dreams, unresponsiveness",

author = "{Van Maldegem}, Milan and Jakub Vohryzek and Selen Atasoy and Naji Alnagger and Paolo Cardone and Vincent Bonhomme and Audrey Vanhaudenhuyse and Athena Demertzi and Oceane Jaquet and Bahri, {Mohamed Ali} and Pablo Nunez and Kringelbach, {Morten L.} and Stamatakis, {Emmanuel A.} and Luppi, {Andrea I.}",

note = "Publisher Copyright: {\textcopyright} 2025 The Author(s)",

year = "2025",

month = apr,

doi = "10.1016/j.bja.2024.12.036",

language = "English",

volume = "134",

pages = "1088--1104",

journal = "British Journal of Anaesthesia",

issn = "0007-0912",

publisher = "Elsevier Ltd",

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Van Maldegem, M, Vohryzek, J, Atasoy, S, Alnagger, N, Cardone, P, Bonhomme, V, Vanhaudenhuyse, A, Demertzi, A, Jaquet, O, Bahri, MA, Nunez, P, Kringelbach, ML, Stamatakis, EA & Luppi, AI 2025, 'Connectome harmonic decomposition tracks the presence of disconnected consciousness during ketamine-induced unresponsiveness', British Journal of Anaesthesia, vol. 134, no. 4, pp. 1088-1104. https://doi.org/10.1016/j.bja.2024.12.036

Connectome harmonic decomposition tracks the presence of disconnected consciousness during ketamine-induced unresponsiveness. / Van Maldegem, Milan; Vohryzek, Jakub; Atasoy, Selen et al.
In: British Journal of Anaesthesia, Vol. 134, No. 4, 04.2025, p. 1088-1104.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Connectome harmonic decomposition tracks the presence of disconnected consciousness during ketamine-induced unresponsiveness

AU - Van Maldegem, Milan

AU - Vohryzek, Jakub

AU - Atasoy, Selen

AU - Alnagger, Naji

AU - Cardone, Paolo

AU - Bonhomme, Vincent

AU - Vanhaudenhuyse, Audrey

AU - Demertzi, Athena

AU - Jaquet, Oceane

AU - Bahri, Mohamed Ali

AU - Nunez, Pablo

AU - Kringelbach, Morten L.

AU - Stamatakis, Emmanuel A.

AU - Luppi, Andrea I.

PY - 2025/4

Y1 - 2025/4

N2 - Background: 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. Methods: 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. Results: 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). Conclusions: 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.

AB - Background: 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. Methods: 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. Results: 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). Conclusions: 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.

KW - connectome harmonics

KW - consciousness

KW - dissociative anaesthesia

KW - functional MRI

KW - ketamine dreams

KW - unresponsiveness

UR - http://www.scopus.com/inward/record.url?scp=85217417870&partnerID=8YFLogxK

U2 - 10.1016/j.bja.2024.12.036

DO - 10.1016/j.bja.2024.12.036

M3 - Journal article

C2 - 39933965

AN - SCOPUS:85217417870

SN - 0007-0912

VL - 134

SP - 1088

EP - 1104

JO - British Journal of Anaesthesia

JF - British Journal of Anaesthesia

IS - 4

ER -

Connectome harmonic decomposition tracks the presence of disconnected consciousness during ketamine-induced unresponsiveness

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