title: Consciousness and Complexity during Unresponsiveness Induced by Propofol, Xenon, and Ketamine.
abstract: A common endpoint of general anesthetics is behavioral unresponsiveness, which is commonly associated with loss of consciousness. However, subjects can become disconnected from the environment while still having conscious experiences, as demonstrated by sleep states associated with dreaming. Among anesthetics, ketamine is remarkable in that it induces profound unresponsiveness, but subjects often report "ketamine dreams" upon emergence from anesthesia. Here, we aimed at assessing consciousness during anesthesia with propofol, xenon, and ketamine, independent of behavioral responsiveness. To do so, in 18 healthy volunteers, we measured the complexity of the cortical response to transcranial magnetic stimulation (TMS)--an approach that has proven helpful in assessing objectively the level of consciousness irrespective of sensory processing and motor responses. In addition, upon emergence from anesthesia, we collected reports about conscious experiences during unresponsiveness. Both frontal and parietal TMS elicited a low-amplitude electroencephalographic (EEG) slow wave corresponding to a local pattern of cortical activation with low complexity during propofol anesthesia, a high-amplitude EEG slow wave corresponding to a global, stereotypical pattern of cortical activation with low complexity during xenon anesthesia, and a wakefulness-like, complex spatiotemporal activation pattern during ketamine anesthesia. Crucially, participants reported no conscious experience after emergence from propofol and xenon anesthesia, whereas after ketamine they reported long, vivid dreams unrelated to the external environment. These results are relevant because they suggest that brain complexity may be sensitive to the presence of disconnected consciousness in subjects who are considered unconscious based on behavioral responses.
authors.affiliation: Dipartimento di Scienze Biomediche e Cliniche "L. Sacco", Università degli Studi di Milano, 20157 Milan, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Sarasso
authors.affiliation: Department of Psychiatry, University of Wisconsin-Madison, Madison, WI 53719, USA; Department of Neurology, University of Wisconsin-Madison, Madison, WI 53705, USA.
authors.forename: Melanie
authors.initials: M
authors.lastname: Boly
authors.affiliation: Dipartimento di Scienze Biomediche e Cliniche "L. Sacco", Università degli Studi di Milano, 20157 Milan, Italy; Dipartimento di Scienze Clinico-chirurgiche, Diagnostiche e Pediatriche, Sezione di Anestesia Rianimazione e Terapia Antalgica, Università degli Studi di Pavia, SC Anestesia e Rianimazione, Fondazione IRCCS Policlinico S. Matteo, 27100 Pavia, Italy.
authors.forename: Martino
authors.initials: M
authors.lastname: Napolitani
authors.affiliation: Department of Psychiatry, University of Wisconsin-Madison, Madison, WI 53719, USA; Coma Science Group, University and University Hospital of Liège, GIGA-Research B34, 4000 Liège, Belgium.
authors.forename: Olivia
authors.initials: O
authors.lastname: Gosseries
authors.affiliation: Coma Science Group, University and University Hospital of Liège, GIGA-Research B34, 4000 Liège, Belgium.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Charland-Verville
authors.affiliation: Dipartimento di Scienze Biomediche e Cliniche "L. Sacco", Università degli Studi di Milano, 20157 Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Casarotto
authors.affiliation: Dipartimento di Scienze Biomediche e Cliniche "L. Sacco", Università degli Studi di Milano, 20157 Milan, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Rosanova
authors.affiliation: Institute of Science and Technology, Federal University of São Paulo, 12231-280 São José dos Campos, Brazil.
authors.forename: Adenauer Girardi
authors.initials: AG
authors.lastname: Casali
authors.affiliation: Department of Anesthesia and Intensive Care Medicine, CHU Sart Tilman University Hospital, University of Liège, 4000 Liège, Belgium.
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Brichant
authors.affiliation: Department of Anesthesia and Intensive Care Medicine, CHU Sart Tilman University Hospital, University of Liège, 4000 Liège, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Boveroux
authors.affiliation: Department of Anaesthesiology, University Hospitals of the KU Leuven, KU Leuven, 3000 Leuven, Belgium; Department of Cardiovascular Sciences, University Hospitals of the KU Leuven, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Steffen
authors.initials: S
authors.lastname: Rex
authors.affiliation: Department of Psychiatry, University of Wisconsin-Madison, Madison, WI 53719, USA.
authors.forename: Giulio
authors.initials: G
authors.lastname: Tononi
authors.affiliation: Coma Science Group, University and University Hospital of Liège, GIGA-Research B34, 4000 Liège, Belgium. Electronic address: steven.laureys@ulg.ac.be.
authors.forename: Steven
authors.initials: S
authors.lastname: Laureys
authors.affiliation: Dipartimento di Scienze Biomediche e Cliniche "L. Sacco", Università degli Studi di Milano, 20157 Milan, Italy; Istituto Di Ricovero e Cura a Carattere Scientifico, Fondazione Don Carlo Gnocchi, 20148 Milan, Italy. Electronic address: marcello.massimini@unimi.it.
authors.forename: Marcello
authors.initials: M
authors.lastname: Massimini
mesh_terms: D000293:Adolescent; D000328:Adult; D000758:Anesthesia; D000778:Anesthetics, Dissociative / Q000494:pharmacology; D018681:Anesthetics, General / Q000494:pharmacology*; D018685:Anesthetics, Inhalation / Q000494:pharmacology; D018686:Anesthetics, Intravenous / Q000494:pharmacology; D003243:Consciousness / Q000187:drug effects*; D004569:Electroencephalography; D005260:Female; D006801:Humans; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D015742:Propofol / Q000494:pharmacology*; D050781:Transcranial Magnetic Stimulation; D014851:Wakefulness / Q000187:drug effects*; D014978:Xenon / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D000778:Anesthetics, Dissociative; D018681:Anesthetics, General; D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D014978:Xenon; D007649:Ketamine; D015742:Propofol