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J Neurosci. 2019 Nov 27. pii: 1910-19. doi: 10.1523/JNEUROSCI.1910-19.2019. [Epub ahead of print]

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

Pal D1,2,3, Li D4,3, Dean JG3,5, Brito MA2,3, Liu T4, Fryzel AM4, Hudetz AG4,2,3, Mashour GA4,2,3.

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Department of Anesthesiology, University of Michigan, 7433 Medical Science Building I, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5615, USA
Neuroscience Graduate Program, University of Michigan, 4137 Undergraduate Science Building, 204 Washtenaw Avenue, Ann Arbor, MI 48109-2215, USA.
Center for Consciousness Science, University of Michigan, Ann Arbor, MI 48109, USA.
Department of Anesthesiology, University of Michigan, 7433 Medical Science Building I, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5615, USA.
Department of Molecular and Integrative Physiology, University of Michigan, 7744 Medical Science Building II, 1137 East Catherine Street, Ann Arbor, MI 48109-5622, USA.


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 (<175 Hz). We show that higher gamma (85-155 Hz) connectivity is decreased (p≤0.02) during sevoflurane anesthesia - an expected finding - but was not restored during wakefulness induced by carbachol delivery to prefrontal cortex. Conversely, for rats in which wakefulness was not restored, the functional gamma connectivity remained reduced but there was a significant decrease (p<0.001) in the power of slow oscillations and increase (p<0.001) in cortical complexity, which was similar to that observed during wakefulness induced after carbachol delivery to prefrontal cortex. We conclude that the level of consciousness can be dissociated from cortical connectivity, oscillations, and dynamics.SIGNIFICANCE STATEMENTNumerous 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.

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