FEATURED ARTICLE

Spotlight on the William L. Young Neuroscience Research Award – Interview with Dr. Miles Berger

Ines P. Koerner, MD, PhD
Chair, SNACC Research Committee

Dr. Miles Berger

Miles Berger, MD, PhD

Ines P. Koerner, MD, PhD
Ines Koerner, MD, PhD, FNCS

Dr. Miles Berger is Assistant Professor of Anesthesiology at Duke University School of Medicine. In 2016, he received the inaugural William L. Young Neuroscience Research Award for his project on the role of brain inflammation in postoperative cognitive dysfunction.

I. Koerner: Why did you choose a career in Neuroanesthesiology?
M. Berger: I knew pretty early on that I wanted to study neuroscience, and that I wanted to take care of patients as a physician. When I was in college, I remember reading about the work of Eric Kandel, who had done pioneering studies demonstrating basic molecular and cellular processes that underlie the formation of simple memories in the sea slug Aplysia. I was doing neutrophil cell biology research at the time, and I thought it was amazing that some of the same signal transduction mechanisms that gave rise to relatively simple cellular behaviors in neutrophils, such as chemotaxis, could also explain the synaptic strengthening mechanisms that underlie memory in organisms ranging from Aplysia to mice to humans.
              
Thus, I started an MD/PhD program with the desire to study neuroscience, and I developed an interest in neuropharmacology in graduate school. I thought about going into psychiatry or neurology, and then I realized that I liked being in the operating room, and that I liked the immediate gratification of being able to administer medications and watch their effects on consciousness in real time. So, in a sense, I knew that I would become a neuroanesthesiologist, i.e. that my future career would focus on clinical neuroscience, even before I decided to go into anesthesiology. Given my interest in neuroscience, once I settled on going into anesthesia as a fourth-year medical student, it was already obvious to me that I wanted to specialize in neuroanesthesiology, due to its focus on the care of patients with neurologic and neurosurgical diseases in particular, and its focus on understanding the neuroscience of anesthesia in general.

I. Koerner: What recommendations do you have for trainees who want to establish themselves as physician-scientists?
M. Berger: The best advice I have ever heard on this topic, and really on life in general, is this: “There are two things in life that matter – work and love. And as long as you love your work, and work on your love, life will treat you well.” As for becoming a physician-scientist, I would say that it is an amazing career path, but not an easy one. There are long days, both on clinical days and on research days, and there is stress, both acute stress in the OR setting, and the more chronic stress of maintaining academic productivity and research funding. But, it is an amazing job; it is amazing to watch how well our drugs work clinically, such as how precisely we can titrate them to facilitate language and motor mapping in awake craniotomy cases. This is a nice example of how neuropharmacokinetic science can be used by anesthesiologists to facilitate what I view as one of the most amazing procedures in all of medicine – the ability to perform near-painless brain surgery in awake patients. Its similarly an amazing privilege to be able to switch roles a day later and go from taking care of patients undergoing procedures like that, to doing translational neuroscience research. My team studies the basis for postoperative neurocognitive disorders in older adults, and we use a variety of tools to do so, from functional MRI to EEG recordings to CSF biomarker studies. Its hard work, but I try to keep in mind an appreciation, a love, for how cool all of this work is, both clinically and scientifically. So, that’s my first piece of advice for trainees who want to be physician-scientists: work on something you love. That love for your work, that passion for what you are studying, is part of what will keep you going when you have a difficult day in the OR, or when you get a paper rejected or when a grant doesn’t get funded. When I was a graduate student, someone asked a similar question to Tom Insel (then the director of the National Institute for Mental Health, who is known for his work on the neuroscience of pair bonding and social behavior). Dr. Insel’s response was that success in science is basically learning how to cope with failure, since so many projects and experiments don’t work. I think it makes it easier to cope with these setbacks if one maintains a larger perspective on the overall importance of the work we are doing, both for increasing our fundamental understanding of the brain and for helping future patients, and a love for one’s work.

The other part of that saying, the part about working on your love, is important too, and perhaps underemphasized in academic medicine. The relationships we have with the people we love are what sustain us and keep us going, especially through life’s challenges. But relationships also take work and can’t be taken for granted. Particularly for physician-scientists, who face the unique and only partly overlapping stresses of being both a physician and a scientist, I think it is important to maintain loving and supportive relationships with our spouses, families and friends, and to put the work needed into nurturing these relationships. I think it is important to recognize this, both for us as individuals and for the institutions at which we work.

I. Koerner: What do you see as the most exciting current topic in neuroanesthesiology?
M. Berger: That’s a tough question, because there are so many exciting current topics. In a very tangible sense, I’m looking forward to the clinical introduction of the next generation of anesthetic drugs, especially sedative-hypnotics such as esterase-cleavable benzodiazepines (such as remimazolam) and etomidate analogues. I think these drugs may allow us to maintain amnesia and unconsciousness with faster returns to consciousness and less off-target side effects (such as hypotension, cardiovascular depression, nausea and vomiting, etc.), especially in older patients.

In a more theoretical sense, I am hoping we will see the fields of consciousness and cognition start to overlap more. There’s a lot of great work that has been done in these two fields separately over the last ~10 years, and I’m hopeful that we will see some merging of these two fields. For example, intraoperative frontal EEG alpha band power has been studied as an inverse correlate of increased age (by Dr. Patrick Purdon and colleagues), and as an inverse correlate of preoperative cognitive status/function by our group and others. Intraoperative EEG alpha band power has also been studied as a potential marker of unconsciousness, which suggests there may some interaction between consciousness and cognition. These two concepts are related in more fundamental ways as well – consciousness can be thought of as a continuous spectrum (rather than as a dichotomous state in which one either is or is not conscious), and there are reasons to think that a greater degree of consciousness may also be associated with greater cognitive function (i.e. greater cognitive abilities). This is a bit outside of what my group studies, but I’m nonetheless interested in learning about what other groups discover in this area in the coming years.

I. Koerner: Can you tell us about your research and how the Bill Young Award supported your success?”
M. Berger: My group studies human perioperative neurocognitive disorders (PND), such as postoperative cognitive dysfunction (POCD, now also called neurocognitive disorder, postoperative) and postoperative delirium. We are particularly interested in the role of cellular neuroinflammation in these disorders. Beautiful work by Dr. Mervyn Maze and my Duke colleague, Dr. Niccolo Terrando, has established that peripheral blood monocytes enter the mouse brain after peripheral orthopedic surgery, and that this brain monocyte influx plays a critical role in postoperative memory deficits in mice. To test whether this mechanism may play a role in human perioperative neurocognitive disorders, my colleagues and I developed a method for purifying cells from human cerebrospinal fluid (CSF) and performing flow cytometry on them; the Bill Young award helped support our early work in developing these methods. We are now using this method to study the association between postoperative CSF monocyte increases and PND, and with the functional MRI connectivity deficits we and others have identified in patients with PND. I am deeply grateful to SNACC for creating and supporting the Bill Young award, not just for how it is helped my own research team, but also for its role in keeping alive the memory and vision of Dr. Bill Young himself – a great neuroanesthesiologist who was taken from us and from his family all too soon. I didn’t know him well, but I was fortunate to have had the chance to meet and talk with Bill several times while I was finishing medical school at UCSF and applying for anesthesiology residency. Bill was a big proponent of the idea that anesthesia research should be defined by what anesthesiologists see fit to study, not the other way around. In other words, the science of anesthesiology should extend far beyond just studying how anesthetic drugs work, into any and all areas of scientific interest to anesthesiologists. I think this is a really important point, and worth keeping alive just as much as our memories of Bill’s gentlemanly, understated and humble persona.

I was thinking recently about this point, and a point made by Dr. Mark Warner of the Mayo clinic several years ago when he was president of the ASA. Dr. Warner pointed out that we as anesthesiologists are the only physicians who modulate and monitor all parts of the human nervous system – the central nervous system (including both the brain and spinal cord – which we modulate via general anesthesia and epidural/spinal techniques), the autonomic nervous system (which we modulate frequently as we control hemodynamics), and the peripheral nervous system (which we modulate via nerve blocks). It’s hard to think of another group of physicians who modulate all of these parts of the human nervous system in a single day. Similarly, and in a larger sense, although we aren’t hematologists, we often transfuse more blood than most hematologists, and we often control ventilator settings more in one day than most pulmonologists, etc. – and the list keeps going. Given this wide breadth of our clinical practice, it is entirely appropriate that our scientific interests should be similarly wide and should not be restricted to just the study of anesthetic drugs themselves (even as important as that topic is). I hope that the Bill Young award will help keep this part of Bill’s scientific philosophy alive for anesthesiologists, and to promote it among young anesthesiologist-scientists who might otherwise feel that their work was too esoteric or unrelated to anesthesia to be considered ‘anesthesia research.’

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