Sleep-like cortical OFF-periods disrupt causality and complexity in the brain of unresponsive wakefulness syndrome patients

M Rosanova,A G Casali,A Pigorini,S Sarasso,G Devalle,M Fecchio,F Seregni,O Gosseries,M Massimini,S Casarotto,O Bodart,S Laureys,G Citerio,A Comanducci,M Boly

doi:10.1038/s41467-018-06871-1

Abstract

Unresponsive wakefulness syndrome (UWS) patients may retain intact portions of the thalamocortical system that are spontaneously active and reactive to sensory stimuli but fail to engage in complex causal interactions, resulting in loss of consciousness. Here, we show that loss of brain complexity after severe injuries is due to a pathological tendency of cortical circuits to fall into silence (OFF-period) upon receiving an input, a behavior typically observed during sleep. Spectral and phase domain analysis of EEG responses to transcranial magnetic stimulation reveals the occurrence of OFF-periods in the cortex of UWS patients (N = 16); these events never occur in healthy awake individuals (N = 20) but are similar to those detected in healthy sleeping subjects (N = 8). Crucially, OFF-periods impair local causal interactions, and prevent the build-up of global complexity in UWS. Our findings link potentially reversible local events to global brain dynamics that are relevant for pathological loss and recovery of consciousness.

Highlights

Unresponsive wakefulness syndrome (UWS) patients may retain intact portions of the thalamocortical system that are spontaneously active and reactive to sensory stimuli but fail to engage in complex causal interactions, resulting in loss of consciousness
We test the following hypotheses: (i) pathological sleep-like OFF-periods occur in the cortex of awake UWS patients and (ii) this mechanism is responsible for the collapse of causality and overall brain complexity associated with loss of consciousness following brain injury
We assessed (1) the occurrence of TMS-evoked slow waves (20 Hz) suppression of EEG power compared to baseline[22,23,24], (2) the impact of the OFF-periods on local causal interactions quantified by means of broadband (>8 Hz) phase-locking factor (PLF), (3) the consequences of the OFFperiod on the build-up of complex global interactions as indexed by the time course of perturbational complexity index (PCI)

Summary

Introduction

Unresponsive wakefulness syndrome (UWS) patients may retain intact portions of the thalamocortical system that are spontaneously active and reactive to sensory stimuli but fail to engage in complex causal interactions, resulting in loss of consciousness. Recent studies employing intracortical stimulation and simultaneous local field potential recordings in humans suggest that the mechanism responsible for this impairment in NREM sleep is the tendency of cortical neurons to fall into a period of suppressed firing (OFF-period) after a transient increase in activity[10,11]. This intrinsic propensity of cortical neurons to fall into OFF-periods has been thoroughly studied in the realm of sleep physiology across species and models and is often referred to as cortical bistability[12,13]. We demonstrate that OFF-periods rapidly disrupt the local causal effects of TMS (as indexed by phase-locking measures) and in turn, the emergence of global complex cortico-cortical interactions (as indexed by PCI)

Methods

Results

Conclusion