Variability of large timescale functional networks in patients with disorders of consciousness.

Objective: Most brain function assessments for disorders of consciousness (DOC) utilized quantified characteristics, measured only once, ignoring the variation of patients' brain states. The study aims to investigate the brain activities of patients with DOC from a new perspective: variability of a large timescale functional network. Methods: Forty-nine patients were enrolled in this study and performed a 1-week behavioral assessment. Subsequently, each patient received electroencephalography (EEG) recordings five times daily at 2-h intervals. Functional connectivity and networks were measured by weighted phase lag index and complex network parameters (characteristic path length, cluster coefficient, and betweenness centrality). The relative coefficient of variation (CV) of network parameters was measured to evaluate functional network variability. Results: Functional networks of patients with vegetative state/unresponsive wakefulness syndrome (VS/UWS) showed significantly higher segregation (characteristic path length) and lower centrality (betweenness centrality) than emerging from the minimal conscious state (EMCS) and minimal conscious state (MCS), as well as lower integration (cluster coefficient) than MCS. The functional networks of VS/UWS patients consistently presented the highest variability in segregation and integration (i.e., highest CV values of characteristic path length and cluster coefficient) on a larger time scale than MCS and EMCS. Moreover, the CV values of characteristic path length and cluster coefficient showed a significant inverse correlation with the Coma Recovery Scale-Revised scores (CRS-R). The CV values of network betweenness centrality, particularly of the cento-parietal region, showed a positive correlation with the CRS-R. Conclusion: The functional networks of VS/UWS patients present the most invariant segregation and integration but divergent centrality on the large time scale networks than MCS and EMCS. Significance: The variations observed within large timescale functional networks significantly correlate with the degree of consciousness impairment. This finding augments our understanding of the neurophysiological mechanisms underpinning disorders of consciousness.