General anesthesia is a drug-induced, reversible condition comprised of five behavioral states: unconsciousness, amnesia (loss of memory), analgesia (loss of pain sensation), akinesia (immobility), and hemodynamic stability with control of the stress response. Our work shows that a primary mechanism through which anesthetics create these altered states of arousal is by initiating and maintaining highly structured oscillations. These oscillations impair communication among brain regions. We illustrate these impressive dynamics by presenting findings from our human studies of general anesthesia using high-density EEG recordings and intracranial recordings. These studies have allowed us to give a detailed characterization of the neurophysiology of loss and recovery of consciousness due to propofol. We show how the oscillatory dynamics change systematically with different anesthetic classes and with age. The age-related changes reflect brain development in children and brain aging in adults. Finally, we demonstrate that the state of general anesthesia can be rapidly reversed by activating specific brain circuits. The success of our research has depended critically on tight coupling of experiments, signal processing research and mathematical modeling. These new insights into the mechanisms of anesthetic action suggest new strategies for using the EEG to monitor the brain states of patients receiving general anesthesia, more principled strategies to dose anesthetics and new approaches to using studies of general anesthesia to gain new, fundamental insights into how the brain works.
Contract Research Organization (Cro)40%