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.

This suggests that TMS-EEG is a reliable tool to discriminate between conscious and unconscious patients at the single subject level. Future works are needed to validate and implement this technique as a clinical tool.

No abstract

Unresponsiveness Wakefulness Syndrome (UWS) patients may retain intact portions of the thalamocortical system that are spontaneously active and responsive to sensory stimuli. In these patients, Transcranial Magnetic Stimulation combined with electroencephalography (TMS/EEG) also reveals preserved cortical reactivity, but in most cases, the residual thalamocortical circuits fail to engage complex causal interactions, as assessed by the perturbational complexity index (PCI).Another condition during which thalamocortical circuits are intact, active and reactive, yet unable to generate complex responses, is physiological non-rapid eye movement (NREM) sleep. The underlying mechanism is bistability: the tendency of cortical neurons to fall into a silent period (OFF-period) upon receiving an input.Here we tested whether a pathological form of bistability may be responsible for loss of brain complexity in UWS patients. Time-frequency decomposition analysis of TMS/EEG responses in UWS patients revealed the occurrence of OFF-periods (detected as a transient suppression of high-frequency oscillations in the EEG) similar to the ones evoked by TMS in the cortex of healthy sleeping subjects. Pathological OFF-periods were detected in any cortical area, significantly impaired local causal interactions (as measured by PLF) and prevented the buildup of global complexity (as measured by PCI) in the brain of UWS patients.Our results draw a first link between neuronal events (OFF-periods) and global brain dynamics (complexity) in UWS patients. To the extent that sleep-like bistability represents the common functional endpoint of loss of complexity, detecting its presence and tracking its evolution over time, may offer a valuable read-out to devise, guide and titrate therapeutic strategies aimed at restoring consciousness.