Neural Correlates of Consciousness in Anesthesia
INSTITUTE: Harvard Medical School/Department of Anesthesia; Massachusetts General Hospital/Department of Anesthesia, Critical Care, and Pain Medicine
PROJECT LEADER: Patrick L. Purdon, Ph.D.
PROJECT DURATION: 2019-2022
LAB WEBSITE: Purdon Lab
This project uses the gift of anesthesia to help us understand the neural correlates of consciousness. Each year, over 60 million patients receive general anesthesia to facilitate surgery and other medical procedures. Anesthetic drugs act at a variety of molecular targets. Different anesthetic drugs seem to produce unconsciousness in different ways, and unconsciousness under any one drug is not a simple on-off switch, but one that has dose-dependent gradations. In this project, we are studying network-level brain dynamics under different anesthetic drugs including propofol and ketamine, in order to understand the many ways in which these drugs disrupt brain activity and consciousness.
Figure 1. Broadband modulation of brain activity by slow oscillations occurs first over posterior cortical regions, extending to frontal cortical regions at higher propofol doses. This implies that anesthetics can disrupt sensory processing distinct from awareness of sensory content at different anesthetic doses. (Stephen, et al., Sci Rep 2020, 2020; 10(1):13701.doi: 10.1038/s41598-020-68756-y)
Broader Impact:
This project will lead to improved medical care of patients who receive general anesthesia for surgery and intensive care. The results will lead directly to an improved understanding of how anesthetic drugs impair consciousness, which in turn will make it possible to monitor anesthesia and deliver it more precisely. Doing so could significantly improve patient outcomes related to delirium, post-operative cognitive dysfunction, post-operative pain management, opioid dependence, and awareness under anesthesia.
Press:
Decoding The Void, Radiolab podcast from WNYC Studios
Brain Music: How 'Fly Me To The Moon' Can Explain Your Brain On Anesthesia, WBUR
Publications:
L. D. Lewis, et al., Rapid fragmentation of neuronal networks at the onset of propofol-induced unconsciousness. Proceedings of the National Academy of Sciences 109, E3377-E3386 (2012)
P.L. Purdon, et al., Electroencephalogram signatures of loss and recovery of consciousness from propofol. Proceedings of the National Academy of Sciences 110, E1142-51 (2013).
E.A. Mukamel, et al., A transition in brain state during propofol induced unconsciousness. Journal of Neuroscience 34, 839-45 (2014).
O. Akeju, et al. Disruption of thalamic functional connectivity is a neural correlate of dexmedetomidine-induced unconsciousness. Elife, 3, e04499 (2014).
P.L. Purdon, et al., The aging brain: An age-dependent analysis of the electroencephalogram during propofol and sevoflurane general anesthesia. British Journal of Anaesthesia 115, i46-i57 (2015).
O. Akeju, et al., Electroencephalogram signatures of ketamine-induced unconsciousness. Clinical Neurophysiology 127, 2414-22 (2016).
F.J. Flores, et al., Thalamocortical synchronization during induction and emergence from propofol-induced unconsciousness. Proc Natl Acad Sci USA, 114, E6660-E6668 (2017).
L.D. Lewis, et al., A transient cortical state with sleep-like sensory responses precedes emergence from general anesthesia in humans. Elife, 7, e33250 (2018).
E.P. Stephen, et al., Broadband slow-wave modulation in posterior and anterior cortex tracks distinct states of propofol-induced unconsciousness. Sci Rep, 10, 13701 (2020).
P.L. Purdon, A. Sampson, K.J. Pavone, E.N. Brown. Clinical electroencephalography for anesthesiologists: Part I: background and basic signatures. Anesthesiology, 123, 937-60 (2015).