Continuous regimens of cortico-motor integration calibrate levels of arousal during emergence from anesthesia

BackgroundRecovery to a conscious state when emerging from anesthesia requires full cortical desynchronization, initiation of movement and behavioral reactivity to sensory stimuli. However, the variety of cortical electroencephalogram (EEG) patterns associated with specific anesthetics and the paucity of behavioral descriptions during emergence from anesthesia have prevented EEG and behavior as feasible tracking methods to assess emerging from anesthesia. We propose a detailed combined analysis of motor and cortical activity to determine levels of arousal in rodents. MethodsUsing decreasing anesthetic concentrations, we simultaneously recorded local field potentials (LFPs) and movement in mice. We delineated cortical dynamics and sub-states during emergence from anesthesia by applying a smoothed-Z score to extract dominant frequencies from spectrogram. Then, we implemented KMeans to obtain cortical sub-states. Finally, we used density estimation and an abrupt change detection algorithm to segment cortical activity into periods. We used cortical sub-states obtained during isoflurane traces to supervise sub-states in sevoflurane and a pharmacologically induced-arousal model. This information together with examining videos were used to categorize behavior. ResultsWe identified five cortical periods with restored motor behavior during emergence from isoflurane anesthetic. Periods of structured sub-states denoted when specific motor behaviors occurred. No significant differences were found when comparing the combined cortical features and motor behavior using isoflurane, sevoflurane and our arousal-rodent model. We describe graded regimens of cortico-motor activity during emergence from anesthesia to assess arousal levels. ConclusionWe show cortical patterns denote gradual motor behaviors when emerging from anesthesia. Restoring motor behavior is a dynamic process that begins tens of minutes earlier than the righting reflex. Combining cortical activity and motor behavior unveils novel biomarkers to accurately track emerging from general anesthesia in rodents and likely other species.