Dexmedetomidine; Hypnotics and Sedatives; Humans; Male; Adult; Female; Young Adult; Nerve Net/drug effects; Nerve Net/diagnostic imaging; Healthy Volunteers; Unconsciousness/chemically induced; Unconsciousness/physiopathology; Deep Sedation/methods; Dexmedetomidine/pharmacology; Consciousness/drug effects; Hypnotics and Sedatives/pharmacology; Magnetic Resonance Imaging; Brain/drug effects; Brain/diagnostic imaging; Brain; Consciousness; Deep Sedation; Nerve Net; Unconsciousness; Anesthesiology and Pain Medicine
Résumé :
[en] [en] BACKGROUND: Human consciousness is generally thought to emerge from the activity of intrinsic connectivity networks (resting-state networks [RSNs]) of the brain, which have topological characteristics including, among others, graph strength and efficiency. So far, most functional brain imaging studies in anesthetized subjects have compared wakefulness and unresponsiveness, a state considered as corresponding to unconsciousness. Sedation and general anesthesia not only produce unconsciousness but also phenomenological states of preserved mental content and perception of the environment (connected consciousness), and preserved mental content but no perception of the environment (disconnected consciousness). Unresponsiveness may be seen during unconsciousness, but also during disconnectedness. Deep dexmedetomidine sedation is frequently a state of disconnected consciousness. In this study, we were interested in characterizing the RSN topology changes across 4 different and steady-state levels of dexmedetomidine-induced alteration of consciousness, namely baseline (Awake, drug-free state), Mild sedation (drowsy, still responding), Deep sedation (unresponsive), and Recovery, with a focus on changes occurring between a connected consciousness state and an unresponsiveness state.
METHODS: A functional magnetic resonance imaging database acquired in 14 healthy volunteers receiving dexmedetomidine sedation was analyzed using a method combining independent component analysis and graph theory, specifically looking at changes in connectivity strength and efficiency occurring during the 4 above-mentioned dexmedetomidine-induced altered consciousness states.
RESULTS: Dexmedetomidine sedation preserves RSN architecture. Unresponsiveness during dexmedetomidine sedation is mainly characterized by a between-networks graph strength alteration and within-network efficiency alteration of lower-order sensory RSNs, while graph strength and efficiency in higher-order RSNs are relatively preserved.
CONCLUSIONS: The differential dexmedetomidine-induced RSN topological changes evidenced in this study may be the signature of inadequate processing of sensory information by lower-order RSNs, and of altered communication between lower-order and higher-order networks, while the latter remain functional. If replicated in an experimental paradigm distinguishing, in unresponsive subjects, disconnected consciousness from unconsciousness, such changes would sustain the hypothesis that disconnected consciousness arises from altered information handling by lower-order sensory networks and altered communication between lower-order and higher-order networks, while the preservation of higher-order networks functioning allows for an internally generated mental content (or dream).
Disciplines :
Anesthésie & soins intensifs
Auteur, co-auteur :
Staquet, Cécile ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'anesthésie - réanimation ; Department of Anaesthetics, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia ; Institute of Academic Surgery, Sydney, New South Wales, Australia ; Donders Institute for Brain Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, Netherlands
Kandeepan, Sivayini; Department of Physics and Astronomy, Western Institute for Neuroscience, University of Western Ontario, London, Ontario, Canada ; Department of Physics, Faculty of Applied Sciences, University of Sri Jayewardenepura, Nugegoda, Sri Lanka
Sanders, Robert D; University of Sydney, Sydney, New South Wales, Australia ; Department of Anaesthetics, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia ; Institute of Academic Surgery, Sydney, New South Wales, Australia
Ribeiro de Paula, Demetrius; Donders Institute for Brain Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, Netherlands
Laureys, Steven ; Université de Liège - ULiège > Département des sciences cliniques
Bonhomme, Vincent ; Université de Liège - ULiège > Département des sciences cliniques > Anesthésie et réanimation ; Department of Anaesthetics, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia ; Institute of Academic Surgery, Sydney, New South Wales, Australia ; Donders Institute for Brain Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, Netherlands
Soddu, Andrea ; Université de Liège - ULiège > Unités de recherche interfacultaires > GIGA-CRC In vivo Imaging (Centre de Recherche du Cyclotron) ; Department of Physics and Astronomy, Western Institute for Neuroscience, University of Western Ontario, London, Ontario, Canada
Langue du document :
Anglais
Titre :
Changes in Intrinsic Connectivity Networks Topology Across Levels of Dexmedetomidine-Induced Alteration of Consciousness.
Funding: This work was supported by Orion Pharma (unrestricted grant of \u20AC11500 and measurement of plasma dexmedetomidine concentrations, Orion Corporation [Business Identity Code FI 19992126], Orionintie 1, PO Box 65, 02200 Espoo, Finland); the Belgian National Funds for Scientific Research (FNRS), where S.L. is research director; the European Commission; the James McDonnell Foundation; the European Space Agency; the Mind Science Foundation; the French Speaking Community Concerted Research Action (ARC \u2013 06/11 \u2013 340); the Public Utility Foundation \u201CUniversit\u00E9 Europ\u00E9enne du Travail\u201D; \u201CFondazione Europea di Ricerca Biomedica\u201D; the University and University Hospital of Liege; the \u201CPlan National Cancer\u201D of Belgium (grant number 138); Belgium Foundation Against Cancer (grant numbers: 2017064 and C/2020/1357); the T\u00E9l\u00E9vie, Benoit Foundation (Bruxelles); Wallonia as part of a program of the BioWin Health Cluster framework; the Natural Sciences and Engineering Research Council of Canada (NSERC) discovery grant; and the University of Western Ontario (London, ON, Canada). Funding sources had no involvement in study design, in collection, analysis, and interpretation of data, in the writing of the report; and in the decision to submit the article for publication.This work was supported by Orion Pharma (unrestricted grant of 11500 and measurement of plasma dexmedetomidine concentrations, Orion Corporation [Business Identity Code FI 19992126], Orionintie 1, PO Box 65, 02200 Espoo, Finland); the Belgian National Funds for Scientific Research (FNRS), where S.L. is research director; the European Commission; the James McDonnell Foundation; the European Space Agency; the Mind Science Foundation; the French Speaking Community Concerted Research Action (ARC-06/11-340); the Public Utility Foundation \"Universite Europeenne du Travail\"; \"Fondazione Europea di Ricerca Biomedica\"; the University and University Hospital of Liege; the \"Plan National Cancer\" of Belgium (grant number 138); Belgium Foundation Against Cancer (grant numbers: 2017064 and C/2020/1357); the Televie, Benoit Foundation (Bruxelles); Wallonia as part of a program of the BioWin Health Cluster framework; the Natural Sciences and Engineering Research Council of Canada (NSERC) discovery grant; and the University of Western Ontario (London, ON, Canada). Funding sources had no involvement in study design, in collection, analysis, and interpretation of data, in the writing of the report; and in the decision to submit the article for publication.
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