AbstractUnderstanding anesthetic mechanisms with the goal of producing anesthetic states with limited systemic side effects is a major objective of neuroscience research in anesthesiology. Coherent frontal alpha oscillations have been postulated as a mechanism of sevoflurane general anesthesia. This postulate remains unproven. Therefore, we performed a single-site, randomized, cross-over, high-density electroencephalogram study of sevoflurane and sevoflurane-plus-ketamine general anesthesia in 12 healthy subjects. Data were analyzed with multitaper spectral, global coherence, cross-frequency coupling, and phase-dependent methods. Our results suggest that coherent alpha oscillations are not fundamental for maintaining sevoflurane general anesthesia. Taken together, our results suggest that subanesthetic and general anesthetic sevoflurane brain states emerge from impaired information processing instantiated by a delta-higher frequency phase-amplitude coupling syntax. These results provide fundamental new insights into the neural circuit mechanisms of sevoflurane anesthesia and suggest that anesthetic states may be produced by extracranial perturbations that cause delta-higher frequency phase-amplitude interactions.