Differential Cortical Network Engagement During States of Un/Consciousness in Humans
Authors: Zelmann Rina , Paulk Angelique , Tian Fangyun , Balanza Gustavo , Peralta Jaquelin Dezha , Crocker Britni , Cosgrove G Rees , Richardson R. Mark , Williams Ziv , Dougherty Darin , Purdon Patrick , Cash Sydney 
Published: September 2022

Abstract
The neural basis of consciousness remains a major unresolved issue in human neuroscience, with theories of consciousness and experimental studies differing concerning which brain regions are necessary for consciousness. Direct experimental evidence to resolve this debate requires identifying the global, network, and regional involvement during different states of consciousness in humans. We utilized multi-region intracranial single-pulse direct electrical stimulation to examine circuit and network interactions during three canonical states of consciousness: wake vs. arousable unconsciousness (sleep) vs. non-arousable unconsciousness (e.g., propofol-induced general anesthesia). Increased variability in cortical responses, reduced information transfer, and reduced complexity characterized states of diminished consciousness. Notably, however, these metrics differed in different brain regions and types of unconscious states.Anesthesia induced more overall changes in brain responses than sleep, but cortical network engagement depended on the kind of unconsciousness. Brain activity changes were largely anatomically uniform during sleep, contrasting with a substantial and selective disconnection of the prefrontal cortices during anesthesia. These results provide direct evidence from human intracranial recordings during the loss of consciousness, suggesting that the obliteration of consciousness during anesthesia results not from just altered overall physiology but from a disconnection between prefrontal areas and other brain areas.
Significance
What happens in the human brain when we are unconscious? Despite substantial work, we are still unsure which brain regions are involved and how they are impacted when consciousness is disrupted. Using intracranial recordings and direct electrical stimulation, we mapped global, network, and regional involvement during wake vs. arousable unconsciousness (sleep) vs. non-arousable unconsciousness (propofol-induced general anesthesia). Information integration and complex processing were reduced, while variability increased during the loss of consciousness. These changes were more pronounced during anesthesia than sleep. They also involved different cortical engagement; During sleep, changes were mostly uniformly distributed across the brain while during anesthesia the prefrontal cortex was the most disrupted. These findings indicate different neural signatures for different types of unconsciousness.
Highlights
· Sleep and anesthesia showed decreased complexity, connectivity, and response amplitude with increased response variability compared to wake states in the human brain.
· These changes in brain response to stimulation were more pronounced during propofol-induced general anesthesia than during natural sleep.
· During sleep, changes were homogeneously distributed across the brain.
· During anesthesia, there was a substantial disconnection of the frontal cortices.