B. AbstractBackground.Despite their intriguing nature, investigations of the neurophysiology of N-methyl-D-aspartate (NMDA)-antagonists Xenon (Xe) and nitrous oxide (N2O) are limited and have revealed inconsistent frequency-dependent alterations, in spectral power and functional connectivity. Discrepancies are likely due to using low resolution electroencephalography restricted to sensor level changes, concomitant anesthetic agent administration and dosage. Our intention was to describe the effects of equivalent stepwise levels of Xe and N2O administration on oscillatory source power using a crossover design, to explore universal mechanisms of NMDA-based anesthesia.Methods.22 healthy males participated in a study of simultaneous magnetoencephalography and electroencephalography recordings. In separate sessions, equivalent subanesthetic doses of gaseous anesthetic agents N2O and Xe (0.25, 0.50, 0.75 equi MAC-awake) and 1.30 MAC-awake Xe (for Loss of Responsiveness) were administered. Source power in various frequency bands was computed and statistically assessed relative to a conscious baseline.Results.Delta (l-4Hz) and theta (4-8Hz) band power was significantly increased at the highest Xe concentration (42%, 1.30 MAC-awake) relative to baseline for both magnetoencephalography and electroencephalography source power (p<0.005). A reduction in frontal alpha (8-13 Hz) power was observed upon N2O administration, and shown to be stronger than equivalent Xe dosage reductions (p=0.005). Higher frequency activity increases were observed in magnetoencephalographic but not encephalographic signals for N2O alone with occipital low gamma (30-49Hz) and widespread high gamma (51-99Hz) rise in source power.Conclusions.Magnetoencephalography source imaging revealed unequivocal and widespread power changes in dissociative anesthesia, which were divergent to source electroencephalography. Loss of Responsiveness anesthesia at 42% Xe (1.30 MAC-awake) demonstrated, similar to inductive agents, low frequency power increases in frontal delta and global theta. N2O sedation yielded a rise in high frequency power in the gamma range which was primarily occipital for lower gamma bandwidth (3049 Hz) and substantially decreased alpha power, particularly in frontal regions.Clinical trial number and Registry URLNot applicable.Prior PresentationsPelentritou Andria, Kuhlmann Levin; Lee Heonsoo; Cormack John; Mcguigan Steven; Woods Will; Sleigh Jamie; Lee UnCheol; Muthukumaraswamy Suresh; Liley David. Searching For Universal Cortical Power Changes Linked To Anesthetic Induced Reductions In Consciousness. The Science of Consciousness April 4th2018. Tucson, Arizona, USA.Summary StatementNot applicable.