October 6, 2021

Disrupting the symphony of consciousness

An earlier passion for philosophy leads George Mashour, M.D., Ph.D., to a distinguished career in anesthesiology and neuroscience.

George Mashour MD, PhD

As a young man, George Mashour was an unlikely candidate to become an internationally renowned physician-scientist in the fields of anesthesiology, neuroscience, and translational science. “I really was not scientifically oriented until I was in my early 20s. I was much more focused on fine arts when I was in high school and liberal arts when I was in college,” says George Mashour, M.D., Ph.D., chair of the U-M Department of Anesthesiology and Robert B. Sweet Professor of Anesthesiology.

"It was actually my study of philosophy and, in particular, the philosophy of Immanuel Kant and his 18th-century work Critique of Pure Reason, that really got me fundamentally interested in consciousness. That's why I ended up going into medicine and neuroscience — and then anesthesiology — to better understand how it is that we are able to have a sense of ourselves, and a sense of the world.”

Mashour earned a doctorate in neuroscience and a medical degree from Georgetown University School of Medicine in Washington, DC, and studied neuroscience as a two-time Fulbright Scholar in Berlin and Bonn, Germany. He completed his internship, residency, and chief residency in anesthesiology at Massachusetts General Hospital, Harvard Medical School, and a fellowship in neurosurgical anesthesiology at the University of Michigan Medical School. 

“The study of consciousness and unconsciousness is a fundamental question in science,” he says. “How is it that the electrical and chemical activity of the brain gives rise to this sense of subjectivity and interiority, a point of view and perspective? It’s also a fundamental existential question. How does the world show up for us when we are awake and how is it suspended when we go to sleep or become anesthetized? I wanted to spend my life thinking about these questions and hopefully make some kind of contribution. So, my story has evolved from different interests and different dimensions that were really rooted more in my earlier passion for philosophy.” 

At the onset of his residency, Mashour turned his focus to the theoretical pursuit of how anesthetics work. “I wanted to use the tools of general anesthetics as a way of better understanding how the brain generates subjective experience,” says Mashour, who holds additional faculty positions as a professor in neurosurgery, pharmacology, and psychology.

“The question that has been around for 175 years is, how do anesthetics, which are structurally and pharmacologically distinct, and which have distinct effects on the brain, result in this common functional outcome of general anesthesia and being ready to have surgery?”

Drawing on his past work in neuroscience, Mashour began to think that it was not the case that anesthetics are simply shutting down neurons in the brain. “It seemed like there actually could be primary sensory processing going on. So early on in my residency I suggested that what anesthetics actually do is disrupt the synthesis of that information,” he says. 

As an example, Mashour references a musical performance. “Think about going to a symphony. You're sitting there and musicians might be practicing their individual parts before a concert, but you're not really hearing music. They’re all doing their own thing. It might be music at the individual level, but collectively, it's cacophony,” says Mashour, a musician in his own right. “And then a conductor comes to the stage, taps on the podium, and starts directing the activity. Suddenly you hear music because you're now experiencing a spatial and temporal integration of all those individual musicians.” 

Mashour considered there might be something similar taking place with consciousness, where the brain, when an individual is awake, is functioning like a symphony.

“There might actually be a kind of conductor in the brain area called the thalamus. And although we don't know exactly what's generating consciousness, we do know that there needs to be this kind of coordination, organization, and integration in the spatial and temporal scales, in order to have that music of consciousness happen,” he says. “Although I started out in theory, we and others have gathered evidence that what anesthetics do is disrupt the integrative process. It's not that they're shutting down the individual musicians per se, but rather disconnecting them and collectively going back to the state of cacophony rather than symphony.” 

When Mashour joined the U-M faculty in 2007, as assistant professor in the departments of Anesthesiology and Neurosurgery, he decided it was time to actually test the effects of anesthetics on the complex systems he’d been looking at.

“That's when I made the move,” says Mashour. “Instead of hiring neuroscientists in my group, I actually hired a physicist. And specifically, a physicist who had expertise in networks and complex systems because I realized I was going to need a quantitative basis to be able to test this network-level approach. Now with scientists from multiple fields, we have worked together to try to understand how anesthetics disrupt that symphony of consciousness while still allowing neurons to keep firing, and maybe even some primary sensory processing to go on. That has been the journey.” 

RECOGNIZING THE IMPACT OF MASHOUR’S RESEARCH 

Mashour has dedicated his career at U-M to the study of consciousness and the mechanisms of unconsciousness across physiologic, pharmacologic, and pathologic conditions. In doing so, he has assembled a multidisciplinary research team comprised of faculty from the disciplines of neuroscience, anesthesiology, physics, network science, engineering, psychology, and philosophy.

In 2013, Mashour transitioned to associate professor, and one year later was named the La Du Professor, before he was promoted to full professor in 2017. He has made notable contributions to the field of anesthesiology, from foundational science on the mechanisms of anesthesia to major clinical trials focused on intraoperative awareness. And nothing is more indicative of these contributions than his recent award, the most prestigious academic honor given within the field of anesthesiology.

In June 2021, Mashour received the American Society of Anesthesiologists Excellence in Research Award for his significant work on the neurobiology of consciousness and unconsciousness, as well as his contributions to academic anesthesiology and translational science. “I'm really truly honored and humbled to receive this award,” he says.

“I'm the fortunate recipient of this award, but I really function as part of a team with some remarkable scholars who have helped shape my thinking, and who help drive the work now. So really this is as much, if not more, about the team as it is about me.”

This September, Mashour was also the recipient of the Society for Neuroscience in Anesthesiology and Critical Care Distinguished Service Award, which is reserved for individuals who have made exceptional contributions to the fields of neuroscience and anesthesiology, and is the highest honor awarded by the society. He received numerous institutional awards, as well as national honors that include the Presidential Scholar Award from the American Society of Anesthesiologists and election to the National Academy of Medicine.  

The Role of Network Dynamics in Consciousness

Since 2008, Mashour and colleagues have worked to characterize the role of networks and network dynamics in human consciousness. “We are working to understand what supports consciousness and the interactions among key brain regions that are involved,” says Mashour, currently the top NIH-funded anesthesiology faculty member in the United States. “Our group was the first to apply formal network science to the study of transitions in consciousness due to anesthetics. The real value of our early work, which was certainly rudimentary in many regards, was that we introduced a new technique and maybe a new way of thinking about it.” 

Investigating Neural Correlates of Consciousness

In 2013, Mashour’s team identified a common neural correlate of anesthetic-induced unconsciousness across propofol, sevoflurane, and ketamine. “We were looking at how the brain shifts from that symphony of consciousness to the cacophony of unconsciousness,” he says. “And we took a principled approach that allowed us to show a consistent neural correlate that was common to three distinct classes of general anesthetics. That pointed us in a new direction. These are findings that have been confirmed in different models and different laboratories and different species. There's a lot more work to be done to be sure, but I think this is a valuable contribution to our understanding of how anesthetics suppress consciousness. To be able to predict that a certain kind of unique anesthetic would have the same effect as the ones that we typically use in the operating room was an exciting finding for us.”

Center for Consciousness Science

In 2014, Mashour founded the U-M Center for Consciousness Science, to advance multidisciplinary research, education, and clinical care as it relates to consciousness. “What I wanted to do, because there were very few centers related to consciousness science, was to create a home at the University of Michigan that could attract people who had an interest in this field but didn’t really have any way of acting on that interest,” says Mashour. “We've built a really great multidisciplinary team. And now it’s so well developed that we’re able to conduct studies of relevance to consciousness that range from computational brain models and rodents to healthy volunteers and surgical patients in clinical trials. And we've had some really interesting studies that have shifted from the laboratory to the clinical arena and vice versa.  I think it's a real differentiator for our institution.”

RADAR

Raising Anesthesiology Diversity and Anti-Racism (RADAR), a partnership between the anesthesiology departments of the University of Michigan and Washington University School of Medicine in St. Louis, is a new national initiative launched in 2020 with the aim to increase diversity and advance anti-racism in academic anesthesiology. “Our mission is to attract college and medical students to the field, provide mentorship and networking opportunities for emerging scholars, and develop resources for department leaders interested in building inclusive and anti-racist communities for learners, faculty, and staff,” he says. “This is really the first initiative that I know of in the field of anesthesiology that is focused on diversity, and not just for a single department, but for the whole field. We have a really promising start and we certainly hope to make some lasting changes as we move forward.”

LOOKING AHEAD

The year 2021 marks the celebration of the 175th anniversary of the first public demonstration of surgery under anesthesia, and Mashour looks ahead with great energy and enthusiasm. “I'm deeply committed to taking our department, and the field of anesthesiology, to the next level, and to redefine the boundaries and roles of an academic anesthesiologist,” he says. “Taking great care of patients as a department, being able to educate the next generation of anesthesiologists and neuroscientists, advancing research at the cutting edge, and helping to create the conditions for others to succeed in those pursuits is really what motivates me.”

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By Barbara Wylan Sefton, Michigan Creative