Level of consciousness is dissociable from electroencephalographic measures of cortical connectivity, slow oscillations, and complexity

Leading neuroscientific theories posit a central role for the functional integration of cortical areas in conscious states. Considerable evidence supporting this hypothesis is based on network changes during anesthesia but it is unclear if these changes represent state-related (conscious vs. unconscious) or drug-related (anesthetic vs. no anesthetic) effects. We recently demonstrated that carbachol delivery to prefrontal cortex restored wakefulness despite continuous administration of the general anesthetic sevoflurane. By contrast, carbachol delivery to parietal cortex, or noradrenaline delivery to either prefrontal or parietal cortices, failed to restore wakefulness. Thus, carbachol-induced reversal of sevoflurane anesthesia represents a unique state that combines wakefulness with clinically relevant anesthetic concentrations in the brain. To differentiate the state-related and drug-related associations of cortical connectivity and dynamics, we analyzed the electroencephalographic data gathered from adult male Sprague Dawley rats during the aforementioned experiments for changes in functional cortical gamma connectivity (25-155 Hz), slow oscillations (0.5-1Hz), and complexity ( SIGNIFICANCE STATEMENT Numerous theories of consciousness suggest that functional connectivity across the cortex is characteristic of the conscious state and is reduced during anesthesia. However, it is unknown whether the observed changes are state-related (conscious vs. unconscious) or drug-related (drug vs. no drug). We employed a novel rat model in which cholinergic stimulation of prefrontal cortex produced wakefulness despite continuous exposure to a general anesthetic. We demonstrate that, as expected, general anesthesia reduces connectivity. Surprisingly, the connectivity remains suppressed despite pharmacologically-induced wakefulness in the presence of anesthetic, with restoration occurring only after the anesthetic is discontinued. Thus, whether an animal exhibits wakefulness or not can be dissociated from cortical connectivity, prompting a re-evaluation of the role of connectivity in level of consciousness.