Mueller, R. N. | bioRxiv Science

bioRxiv2025

Dexmedetomidine produces more sleep-like brain activity compared to propofol

IntroductionDexmedetomidine is a selective 2-adrenergic agonist used as an anesthesia adjunct to produce a state of sleep-like sedation. However, how brain activity compares quantitatively during dexmedetomidine anesthesia to that during natural sleep, and thus just how "sleep-like" dexmedetomidine anesthesia is, remains unclear. Previously, we showed that the general anesthetic propofol is associated with changes in connectivity and cortical network structure comparable to those observed during sleep. Here, we compare the effects on brain activity of dexmedetomidine, propofol, and sleep quantitatively using intracranial encephalographic (iEEG) recordings in human research participants. MethodsiEEG recordings were obtained in 34 epilepsy patients being evaluated for potential seizure resection surgery. Band power and functional connectivity (alpha weighted phase lag index, gamma envelope correlations) and network entropy were measured in recordings during task-free ("resting state") periods just prior to surgery during anesthesia with either dexmedetomidine or propofol, and during overnight sleep. Anesthesia stage (wake, sedated, unresponsive) was determined using the Observers Assessment of Arousal and Sedation. Sleep was staged using standard polysomnography. ResultsAs expected, significant differences in delta power were observed during dexmedetomidine and propofol as well as during sleep. However, the magnitude of changes in delta power were smaller and regionally heterogeneous for propofol compared to dexmedetomidine and sleep. Functional connectivity changes were comparable between dexmedetomidine, propofol, and natural sleep. Significant changes in network entropy were observed for dexmedetomidine, propofol, and sleep, but changes were larger for propofol compared to dexmedetomidine and sleep. Quantitative comparisons between changes in delta power and network entropy suggest that unresponsiveness under dexmedetomidine produces a similar brain state to that observed during N2 sleep. ConclusionsWhile delta power, functional connectivity, and network entropy all showed changes during propofol, dexmedetomidine, and sleep, the magnitudes of these changes suggest that dexmedetomidine is more similar than propofol to sleep, specifically to N2 sleep.

neuroscience↗

bioRxiv2022

Consciousness is indexed by analogous cortical reorganization during sleep and anesthesia

Although sleep and anesthesia are predicted to share common neural signatures of transitions into and out of unconsciousness, supportive evidence has been elusive. We identified these signatures using intracranial electroencephalography in neurosurgical patients. We applied diffusion map embedding to map cortical location into a space where proximity indicates functional similarity using a normalized connectivity ( diffusion) matrix, itself a rich source of information about network properties. During reduced consciousness, diffusion matrices exhibited decreased effective dimensionality, reflecting reduced network entropy. Furthermore, functional brain regions exhibited tighter clustering in embedding space with greater distances between regions, corresponding to decreased differentiation and functional integration. These changes were not region-specific, suggesting global network reorganization. These results strongly suggest common neural substrates for loss and recovery of consciousness during anesthesia and sleep, providing a systems-level mechanistic understanding within an intuitive geometric context and laying the foundation for evaluation of cortical state transitions in clinical settings.

neuroscience↗