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

Abstract

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.

Paradoxical cognitive and language function recovery by zolpidem in a patient with traumatic brain injury: A case report

“…[35] Matt Heath utilized functional MRI to demonstrate increased cortical activity in patients with brain injuries post-zolpidem administration, indicating enhanced neural network activity. A similar enhancement was detected in electroencephalograms, [36,37] suggesting that zolpidem may influence neural network connections and cerebral blood flow, thereby underscoring its potential role in boosting neural activity and functional recovery in specific brain regions.…”

Uncovering Brain Network Insights for Prognosis in Disorders of Consciousness: EEG Source Space Analysis and Brain Dynamics

“…Second, as a dynamic system, the brain presents a research gap regarding whether brain networks underlying different brain states have the same or similar prognostic utility. Previous studies have shown that brain injuries can lead to significant alterations in brain dynamic parameters (e.g., mean state duration and mean state interval [18], [24]), but they do not necessarily result in marked alterations to the EEG brain state templates (e.g., EEG topographic maps corresponding to cluster centroids [18], [24]). Research on the prognostic abilities of brain networks underlying different brain states will provide opportunities for the identification of novel biomarkers and a deeper understanding of brain dynamics.…”

Alleviating sleep disturbances and modulating neuronal activity after ischemia: Evidence for the benefits of zolpidem in stroke recovery

“…However, despite being a fast‐acting sleep‐promoting drug with few side effects, little attention has been paid to its hypnotic effect on stroke subjects. To the best of our knowledge, available data on the effects of zolpidem on sleep in patients with brain injury are from patients years after brain damage 25–29 . The latest data were published by Hao et al., 27 in which the authors reported zolpidem‐induced EEG spectral features in eight patients (four stroke survivors) 4.5 months after brain injury.…”

“…To the best of our knowledge, available data on the effects of zolpidem on sleep in patients with brain injury are from patients years after brain damage. 25 , 26 , 27 , 28 , 29 The latest data were published by Hao et al., 27 in which the authors reported zolpidem‐induced EEG spectral features in eight patients (four stroke survivors) 4.5 months after brain injury. Thus, in both animal models and clinical trials, there is currently little data available on the effects of zolpidem on sleep characteristics and sleep efficiency in stroke victims during the subacute phase, a critical stage for reducing neuronal death and boosting brain repair.…”