Cerebral mechanisms of general anesthesia

How does general anesthesia (GA) work? Anesthetics are pharmacological agents that target specific central nervous system receptors. Once they bind to their brain receptors, anesthetics modulate remote brain areas and end up interfering with global neuronal networks, leading to a controlled and reversible loss of consciousness. This remarkable manipulation of consciousness allows millions of people every year to undergo surgery safely most of the time. However, despite all the progress that has been made, we still lack a clear and comprehensive insight into the specific neurophysiological mechanisms of GA, from the molecular level to the global brain propagation. During the last decade, the exponential progress in neuroscience and neuro-imaging led to a significant step in the understanding of the neural correlates of consciousness, with direct consequences for clinical anesthesia. Far from shutting down all brain activity, anesthetics lead to a shift in the brain state to a distinct, highly specific and complex state, which is being increasingly characterized by modern neuro-imaging techniques. There are several clinical consequences and challenges that are arising from the current efforts to dissect GA mechanisms: the improvement of anesthetic depth monitoring, the characterization and avoidance of intra-operative awareness and post-anesthesia cognitive disorders, and the development of future generations of anesthetics.