EDITORIAL ANESTHESIOLOGY, V 136 • NO 3 MARCH 2022 405 Image: J. P. Rathmell. This editorial accompanies the article on p. 420. Accepted for publication December 6, 2021. From the Center for Consciousness Science, Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, Michigan (G.A.M., U.L.); Central Clinical School, Sydney Medical School, University of Sydney, Camperdown, New South Wales, Australia (R.D.S.); and Department of Anesthetics and Institute of Academic Surgery, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia (R.D.S.). Copyright © 2022, the American Society of Anesthesiologists. All Rights Reserved. Anesthesiology 2022; 136:405–7. DOI: 10.1097/ALN.0000000000004110 Propofol Anesthesia: A Leap into the Void? George A. Mashour, M.D., Ph.D., Robert D. Sanders, M.B.B.S., Ph.D., F.R.C.A., UnCheol Lee, Ph.D. F or the greater part of the 20th century, research into the mechanisms of general anesthe- sia focused on biomolecular tar- gets such as lipids and proteins. In the mid-1990s, this approach was complemented by emerging stud- ies of anesthetic mechanisms based on systems neuroscience, which has thus far been a major focus in the 21st century. This line of investigation extends beyond the molecular and biophysical focus to the study of neural circuits and the properties of large-scale brain networks, as assessed, for example, by functional magnetic resonance imaging and electroen- cephalography. For the past 15 yr, neuroimaging and neurophysio- logic data during anesthetic state transitions have been increasingly analyzed with measures of func- tional connectivity (how activities of diferent brain regions co-vary), directional or efective connectivity (how activities in one brain region infu- ence that of another), and global network properties (how interconnected nodes behave in terms of overall efciency and organization). 1 Despite remarkable progress, questions remain, including how these various connectivity and net- work properties unfold during the induction of general anesthesia. Does the brain experience a smooth slide to the depths of oblivion? Or is there a kind of quantum leap into the void? In this issue of Anesthesiology, the study from Pullon, Warnaby, and Sleigh helps address this very quan- dary. 2 The investigators reanalyzed data from a study of 16 healthy human volunteers who underwent a slow induc- tion of propofol anesthesia while multichannel electroen- cephalography was recorded. Behavioral responsiveness was assessed by a command and button-pressing; after general anesthesia was established, passive emergence (rather than a symmetrical down-titration of propofol) was permitted. After the experiment, the inves- tigators used the electroencepha- lographic data to assess functional connectivity, i.e., how the neuro- physiologic activity around one electrode relates to—or coheres with—that of a more distant elec- trode. By way of analogy, imagine the three authors of this Editorial singing in harmony. Our activity (singing) would be functionally connected (harmony) even if we were not infuencing one another directly because we were all read- ing from a single musical score. The investigators also measured a surrogate of shared information evident in the neurophysiologic signal and they analyzed network properties such as efciency and clustering (i.e., how many of a node’s connections have connec- tions with each other, like a close- knit group of friends). Finally, they analyzed complexity in the neurophysiologic signal, refect- ing the diversity of activity across the brain.To complement these empirical studies, they also used a well-known com- putational model of oscillatory activity to link their empir- ical connectivity and complexity measures to an important dynamic feature of networks known as criticality. Criticality is when a system is poised on the boundary of order and disorder. In neurobiological terms, the advantage of dancing on this fne line is that the brain can fexibly respond to incoming stimuli without being entrenched in any one set of activities. Although these analytic techniques have all been employed before in the context of anesthetic state transi- tions, what is new in the article from Pullon et al. 2 is the joint consideration of these network properties in the context of a slow, carefully controlled induction of propofol anesthe- sia. The gradual ramp-up of propofol infusion is important because a bolus dose would induce a rapid network change “[In anesthesia] does the brain experience a smooth slide to the depths of oblivion? Or is there a kind of quantum leap into the void?” Copyright © 2022, the American Society of Anesthesiologists. All Rights Reserved. Unauthorized reproduction of this article is prohibited. <zdoi;. DOI: 10.1097/ALN.0000000000004110> Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/136/3/405/533421/20220300.0-00008.pdf by guest on 03 May 2023