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

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