Study protocol: Cerebral characterization of sensory gating in disconnected dreaming states during propofol anesthesia using fMRI

Front Neurosci. 2024 Feb 13:18:1306344. doi: 10.3389/fnins.2024.1306344. eCollection 2024.

Abstract

Background: Disconnected consciousness describes a state in which subjective experience (i.e., consciousness) becomes isolated from the external world. It appears frequently during sleep or sedation, when subjective experiences remain vivid but are unaffected by external stimuli. Traditional methods of differentiating connected and disconnected consciousness, such as relying on behavioral responsiveness or on post-anesthesia reports, have demonstrated limited accuracy: unresponsiveness has been shown to not necessarily equate to unconsciousness and amnesic effects of anesthesia and sleep can impair explicit recollection of events occurred during sleep/sedation. Due to these methodological challenges, our understanding of the neural mechanisms underlying sensory disconnection remains limited.

Methods: To overcome these methodological challenges, we employ a distinctive strategy by combining a serial awakening paradigm with auditory stimulation during mild propofol sedation. While under sedation, participants are systematically exposed to auditory stimuli and questioned about their subjective experience (to assess consciousness) and their awareness of the sounds (to evaluate connectedness/disconnectedness from the environment). The data collected through interviews are used to categorize participants into connected and disconnected consciousness states. This method circumvents the requirement for responsiveness in assessing consciousness and mitigates amnesic effects of anesthesia as participants are questioned while still under sedation. Functional MRI data are concurrently collected to investigate cerebral activity patterns during connected and disconnected states, to elucidate sensory disconnection neural gating mechanisms. We examine whether this gating mechanism resides at the thalamic level or results from disruptions in information propagation to higher cortices. Furthermore, we explore the potential role of slow-wave activity (SWA) in inducing disconnected consciousness by quantifying high-frequency BOLD oscillations, a known correlate of slow-wave activity.

Discussion: This study represents a notable advancement in the investigation of sensory disconnection. The serial awakening paradigm effectively mitigates amnesic effects by collecting reports immediately after regaining responsiveness, while still under sedation. Ultimately, this research holds the potential to understand how sensory gating is achieved at the neural level. These biomarkers might be relevant for the development of sensitive anesthesia monitoring to avoid intraoperative connected consciousness and for the assessment of patients suffering from pathologically reduced consciousness.

Clinical trial registration: European Union Drug Regulating Authorities Clinical Trials Database (EudraCT), identifier 2020-003524-17.

Keywords: disconnected consciousness; propofol sedation; sensory gating; serial awakening paradigm; slow wave activity.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The study was supported by the Mind Science Foundation-Tom Slick Research Award granted to BC, JA, VB, and SL; the Belgian National Funds for Scientific Research (FRS-FNRS); the Fondation Leon Fredericq ("Crédit classique", "Crédits forfaitaires" and "Bourse de fonctionnement"); the University and University Hospital of Liège; the Department of Anesthesia and Intensive Care Medicine, Liege University Hospital, Belgium. The study was further supported by the European Union's Horizon 2020 Framework Programme for Research and Innovation under the Specific Grant Agreement no. 945539 (Human Brain Project SGA3), the FNRS PDR project (T.0134.21), FNRS - MIS project F.4521.23, FNRS - MIS project F.4521.23, the ERA-Net FLAG-ERA JTC2021 project ModelDXConsciousness (Human Brain Project Partnering Project), the fund Generet, the King Baudouin Foundation, the Télévie Foundation, the Public Utility Foundation “Université Européenne du Travail”, "Fondazione Europea di Ricerca Biomedica", the BIAL Foundation, the European Commission, the Mind-Care foundation, the National Natural Science Foundation of China (Joint Research Project 81471100) and the European Foundation of Biomedical Research FERB Onlus. BC is doctoral candidate at the GIGA Doctoral School for Health Science (University of Liege) and FNRS-ASP. LL is supported by the EU Joint Programme Neurodegenerative Disease Research (JPND) (SCAIFIELD project – FNRS reference: PINT-MULTI R.8006.20). OG is Research Associate at FRS-FNRS. CP and SL are Research Directors at FRS-FNRS. SL is supported by the Human Brain Project, National Natural Science Foundation of China, European Foundation of Biomedical Research FERB Onlus, fund Generet of King Baudouin Foundation, Mind Care International Foundation. JA is postdoctoral fellow funded (1265522N) by the Fund for Scientific Research-Flanders (FWO).