Cross-frequency brain functional network analysis of auditory stimulation in acute disorders of consciousness

Currently, prognostic assessment for patients with acute disorders of consciousness (DOC) remains a key and challenging focus in neuroscience. Existing research has predominantly concentrated on brain functional connectivity within specific frequency bands, overlooking the potential role of cross-frequency coupling (CFC). To address this, this study systematically analyzed within-frequency coupling (WFC) and CFC in 38 patients with acute DOC (18 cases transitioning to minimally conscious state (MCS) and 20 cases to vegetative state (VS) in the prolonged phase) based on electroencephalogram (EEG) signals recorded during auditory name‑calling stimulation. Furthermore, WFC brain networks and two‑layer functional brain networks incorporating both WFC and CFC were constructed to investigate their association with consciousness prognosis. The results revealed that, compared to the VS group, the MCS group exhibited significantly stronger WFC in the alpha band but significantly weaker WFC in the delta and theta bands, as well as reduced delta-theta and theta-beta CFC. These differences were more pronounced in the frontal‑parietal regions. Graph theoretical analysis indicated that the MCS group exhibited significantly higher small‑world properties in the alpha band and the cross-frequency theta-beta and alpha-beta networks, suggesting better‑preserved information processing efficiency in their brain networks. These findings demonstrate that CFC and multilayer network topological properties hold significant potential in characterizing the level of consciousness in acute DOC, and may offer new electrophysiological insights for early prognostic evaluation.