• 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, and Andrea I Luppi.
• Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK; Department of Physiology, Development & Neuroscience, University of Cambridge, Cambridge, UK; Division of Anaesthesia, University of Cambridge, Cambridge, UK. Electronic address: mv554@cam.ac.uk.
• Br J Anaesth. 2025 Feb 10.

BackgroundKetamine, 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.MethodsThe 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.ResultsAn 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).ConclusionsThe 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.Copyright © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved.

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