Fig. 3: Cortical bistability in awake brain-injured patients.

A TMS-EEG in unresponsive wakefulness syndrome patients shows the presence of bistability impacting the ability of cortical circuits to engage in stable, reciprocal interactions and explains the breakdown of effective connectivity and network complexity. As in NREM sleep, due to the presence of severe multifocal brain injuries (black shades), cortical responses to TMS in awake patients with UWS are characterized by a dramatic breakdown of long-range recurrent interactions and spatiotemporal dynamics (left column). Locally, these responses match the electrophysiological criteria for the detection of an OFF-period (i.e., the presence of a stereotypical slow wave, associated with a suppression of high-frequency power >20 Hz), and are invariably found in every stimulated cortical region (right column). B The clinical transition from UWS (left column) to the recovery of functional communication (right column) is characterized by a disappearance of the OFF-period, paralleled by an increase in the duration of causal interactions (as indexed by phase-locking measures) and, in turn, by a recovery of complex spatiotemporal dynamics, reflected in high values of PCI. C EEG slowing is often present in areas surrounding focal cortical lesions in awake stroke patients. D The application of TMS reveals local full-fledged signs of sleep-like cortical bistability (i.e., the presence of local stereotypical slow wave, associated with the suppression of high-frequency power >20 Hz) over perilesional areas (left and middle column) that are not detectable when stimulating the same cortical region over the contralesional hemisphere (right column). For all panels, EEG activity is presented from six representative electrodes (yellow disks in panels A, C, D) uniformly distributed along the antero-posterior axis of the two hemispheres. The red trace in panels A, B, D highlights the EEG recorded from the channel closest to the TMS coil.