CORE A. DATA ANALYSIS General anesthesia is a fascinating man-made, neurophysiological phenomenon that has been developed empirically over many years to enable safe and humane performance of surgical and non-surgical procedures. Specifically it is a drug-induced condition consisting of unconsciousness, amnesia, analgesia and immobility, along with physiological stability. General anesthesia is administered daily to 60,000 patients in the United States, the mechanisms for how anesthetics act in the brain to create the states of anesthesia are not well understood. Significant progress has been made recently in characterizing the molecular sites that anesthetics target. However, how actions at specific molecular targets lead to the behavioral states is less well understood. Addressing this issue requires a systems neuroscience approach to define how actions of the drugs at specific molecular targets and neural circuits lead to a behavioral state of general anesthesia. In this program project entitled, Integrated Systems Neuroscience Studies of Anesthesia, we will develop an integrated systems neuroscience program consisting of human, non-human primate, rodent and modeling studies of four anesthetics: the GABAA agents, propofol and sevoflurane; the alpha-2 adrenergic agonist, dexmedetomidine; and the NMDA receptor antagonist, ketamine. The program project will also include a DATA ANALYSIS CORE, which will provide assistant with data analysis and conduct research on statistical methods. The Specific Aims are to understand how the actions of the anesthetics at specific molecular targets and neural circuits produce the oscillatory dynamics (EEG rhythms, changes in LFPs and neural spiking activity) that are likely a primary common mechanism through which anesthetics create altered states of arousal (sedation, hallucination, unconsciousness). The research in this center will produce volumes of neural spike train, EEG, local field potential and behavioral data. Therefore, the DATA ANALYSIS CORE will be a central project in this program. Investigators working in the DATA ANALYSIS CORE will assist the experimentalist with their data analyses and help with data and algorithm cataloguing. The analyses conducted by these investigators will provide specific quantitative constrains that will greatly facilitate the modeling research. Research in the DATA ANALYSIS CORE will develop statistical methods and signal processing algorithms in three areas that are directly relevant to the data that will be recorded in these studies: simultaneous analysis of multiple neural spike trains; dynamic analysis of phase-amplitude modulation; and source localization from high-density EEG recordings. These studies will also provide fundamental new quantitative knowledge about the neurophysiology of the brain's arousal circuits that will be relevant to studies of other neuropsychological problems such as coma, pain, sleep and depression. The signal processing algorithms and statistical techniques can also be applied to problems in areas of science and engineering.