EEG Evidence Reveals Zolpidem-Related Alterations and Prognostic Value in Disorders of Consciousness

Effective treatment and accurate long-term prognostication of patients with disorders of consciousness (DOC) remain pivotal clinical issues and challenges in neuroscience. Previous studies have shown that zolpidem produces paradoxical recovery and induces similar change patterns in specific electrophysiological features in some DOC (∼6%). However, whether these specific features are neural markers of responders, and how neural features evolve over time remain unclear. Here, we capitalized on static and dynamic EEG analysis techniques to fully uncover zolpidem-induced alterations in eight patients with DOC and constructed machine-learning models to predict long-term outcomes at the single-subject level. We observed consistent patterns of change across all patients in several static features (e.g., decreased relative theta power and weakened alpha-band functional connectivity) after zolpidem administration, albeit none zolpidem responders. Based on the current evidence, previously published electrophysiological features are not neural markers for zolpidem responders. Moreover, we found that the temporal dynamics of the brain slowed down after zolpidem intake. Brain states before and after zolpidem administration could be completely characterized by the EEG features. Furthermore, long-term outcomes were accurately predicted using connectivity features. Our findings suggest that EEG neural signatures have huge potential to assess consciousness states and predict fine-grained outcomes. In summary, our results extend the understanding of the effects of zolpidem on the brain and open avenues for the application prospect of zolpidem and EEG in patients with DOC.