Arousal, which integrates cortical, autonomic and behavioral activations, underlies all cognitive functions. Thus, perturbations of arousal are associated with impaired perception and reaction of individuals, the worst case is coma. Coma is a vastly low arousal state, characterized by absence of behavior and prominently suppressed brain activities. As for emergence from coma, stimulating recovery and determining if the patient is recovering or has the potential to recover are clinically and ethically crucial. Accordingly, animal models and anesthesia emergence are critical to identify neural circuits restoring arousal and biomarkers assessing arousal. Although multiple nuclei have been identified to re-establish arousal from anesthesia, they are inadequate to arouse subjects from a significantly lower state such as coma. To overcome this, the first part of this thesis identified a subpopulation of nucleus gigantocellularis (NGC) in the brainstem capable of eliciting high degree of wakefulness from coma in rodents, represented by cortical high frequency activity concurrent with organized movement and behavioral reactivity to stimuli. These integrative cortico-motor features equate to full correlates of wakefulness in human, compared with current criterion that hinges on reflex. NGC stimulation showed behavioral heterogeneity across animals, ranging from simple twitches to disorganized limb movement to organized full body movement (optimal recovery). To measure variability of arousal, current criterion that produces binary outcome of awake versus not awake is insufficient. To establish a non-binary measure of arousal, the second part of this thesis repeatedly integrated cortico-motor features and derived five characterized cortical periods accompanied by the motor recovery that calibrate levels of arousal. The obtained cortico-motor regimes were demonstrated to be consistent across subjects and comatose models. The consistency of cortico-motor regimes implied that recovery from diverse comatose states probably shares a common restoration of cortico-motor traits, which potentiated a universal biomarker to track the recovery. To test this hypothesis, for the third time we integrated cortico-motor features and identified arousal units, electroencephalograms that integrated cortical desynchronization, autonomic activation and onset of single movement. Automated algorithms were developed to transform arousal units into trackable and quantitative measures of arousal levels (termed arousal index), thus depicting trajectory of recovery. To summarize, this thesis identifies an essential nucleus (NGC) capable of awakening animals from coma. Inferring wakefulness after NGC stimulation then initiates a chain reaction of integrated cortico-motor features that constantly boost assessment of arousal in rodents, from reflex to cortical high frequency reactivation-organized movement to cortico-motor regimes (nonbinary) then to arousal index (quantitative and trackable), which bridge the gap and further surpass assessment of arousal in human and facilitate animal models in pre-clinical investigations of coma emergence.