Brain-scale cortico-cortical functional connectivity in the delta-theta band is a robust signature of conscious states: an intracranial and scalp EEG study

Pierre Bourdillon,Jacobo Sitt,Hélène Bastuji,Jean-Rémi King,Jean Isnard,Marc Guénot,Lionel Naccache,Bertrand Hermann

doi:10.1038/s41598-020-70447-7

Abstract

Long-range cortico-cortical functional connectivity has long been theorized to be necessary for conscious states. In the present work, we estimate long-range cortical connectivity in a series of intracranial and scalp EEG recordings experiments. In the two first experiments intracranial-EEG (iEEG) was recorded during four distinct states within the same individuals: conscious wakefulness (CW), rapid-eye-movement sleep (REM), stable periods of slow-wave sleep (SWS) and deep propofol anaesthesia (PA). We estimated functional connectivity using the following two methods: weighted Symbolic-Mutual-Information (wSMI) and phase-locked value (PLV). Our results showed that long-range functional connectivity in the delta-theta frequency band specifically discriminated CW and REM from SWS and PA. In the third experiment, we generalized this original finding on a large cohort of brain-injured patients. FC in the delta-theta band was significantly higher in patients being in a minimally conscious state (MCS) than in those being in a vegetative state (or unresponsive wakefulness syndrome). Taken together the present results suggest that FC of cortical activity in this slow frequency band is a new and robust signature of conscious states.

Highlights

Long-range cortico-cortical functional connectivity has long been theorized to be necessary for conscious states
In line with our original study, weighted Symbolic Mutual Information (wSMI) computed in the 4–10 Hz (τ = 32 ms) succeeded to distinguish conscious wakefulness (CW) from slow-wave sleep (SWS) in all patients in whom long lasting sleep recording was analysed during the first study: mean wSMI 4–10 Hz computed across all bipolar contacts combinations was larger during CW than during SWS (t-test p < 0.001 for each patient)
In the present iEEG and EEG study, we first showed that long-range cortico-cortical connectivity measured with the wSMI computed in the theta-alpha band (4–10 Hz),that was previously shown to be higher for patients in the minimally conscious state (MCS) from those in the vegetative state/unresponsive wakefulness syndrome (VS/UWS), was larger during CW than during SWS

Summary

Introduction

Long-range cortico-cortical functional connectivity has long been theorized to be necessary for conscious states. We excluded transitional periods between SWS and REM, as well as stage 2 SWS that have been associated with some sparse and elementary dream experience[14] Another argument supporting our approach originates from a series of TMS-EEG studies by Massimini and colleagues[17,18,19]. They reliably demonstrated that after a focal single pulse of TMS delivered to a focal cortical region elicited an early, focal and transient response both in CW and in various unconscious states including deep general anesthesia with several drugs, SWS, VS/UWS and comatose state, whereas only CW was associated with later cortical response. King and colleagues conceived wSMI, and used this measure to distinguish conscious and minimally

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