Sleep-like bistability, loss of causality and complexity in the brain of Unresponsive Wakefulness Syndrome patients

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

doi:10.1101/242644

bioRxiv · 10.1101/242644

Sleep-like bistability, loss of causality and complexity in the brain of Unresponsive Wakefulness Syndrome patients

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

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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 build-up 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.

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Rosanova, M., Fecchio, M., Casarotto, S., Sarasso, S., Casali, A. G., Pigorini, A., Comanducci, A., Seregni, F., Devalle, G., Bodart, O., Boly, M., Gosseries, O., Laureys, S., Massimini, M.. 2018-01-04. Sleep-like bistability, loss of causality and complexity in the brain of Unresponsive Wakefulness Syndrome patients. https://doi.org/10.1101/242644

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