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Spotlight on the William L. Young Neuroscience Research Award – An Interview with Andrew Hudson, MD, PhD

Ines Koerner, MD, PhD

Ines Koerner, MD, PhD

Andrew E. Hudson, MD

Andrew E. Hudson, MD

Ines Koerner, MD, PhD
Chair of Research Committee

Dr. Andrew E. Hudson is Assistant Professor in Residence of Anesthesiology and Perioperative Medicine and Director of Neuroscience Research at UCLA. In 2017, he received the William L. Young Neuroscience Research Award for his project on the role of burst suppression in the cortical microcircuit.

Dr. Koerner: Why did you choose a career in neuroanesthesiology?

Dr. Hudson: I became interested in neuroscience as an undergraduate at the University of California, Berkeley. After an early flirtation with physics, I became fascinated by the problem of how the brain gives rise to the mind. I found it fascinating to follow the hints that we have from language about the structure of thought and the constraints that our subjective experience can place on our explanatory theories of mind. Yet it became clear to me that the best way to make any headway on the mind-body problem was to focus on neurobiology, and specifically the neurobiology of disorders of consciousness.

As a result, I sought out a combined MD-PhD program where I could get clinical exposure to disorders of consciousness and a PhD in neurophysiology. After completing my PhD, I reentered my clinical rotations with the notion of specializing in neurology or neurosurgery, given my organic interest in the brain. I liked the functional anatomy of neurology and the instant gratification of the procedures in neurosurgery, but neither quite clicked. I found my anesthesiology rotation exciting with profound consequences for patient outcomes; moreover, I could watch patients lose and recover consciousness multiple times a day, which meant that clinical anesthesiology provided a laboratory for studying the loss and recovery of consciousness in intact brains. My understanding of neurophysiology, together with my enjoyment of neurosurgical procedures, made neuroanesthesiology a natural fit.

Dr. Koerner: What recommendations do you have for trainees who want to establish themselves as physician-scientists?  

Dr. Hudson: If I had only one piece of advice, it would be to aim to be truly excellent. Take your clinical training and become the best clinician you can be. Be the best researcher you can be. That pursuit of excellence is in and of itself is an act of leadership that will get you noticed within your local community. It is also much easier to be accepted by your colleagues when they see you do great work.

Each of us will take our own road to establishing ourselves. That road may be winding and might take you to a different destination than you expect. But those diversions can be real highlights of the journey. To make sense of what is a worthwhile diversion and what is a dead end, you really need the help of multiple mentors. I have been lucky to have had wonderful mentors over the years that have challenged me, helped me define my values, and helped me understand what is important within my institutional context. To that end it is helpful to understand the yardsticks that will be used to evaluate your performance, so you can be sure you are measuring up.

I would like to point out that, while some of my mentors have been local, I have multiple mentors in the SNACC community. Right now, academic anesthesiology, and particularly anesthetic neuroscience, is a wonderful and supportive community.

Dr. Koerner: What do you see as the most exciting current topic in neuroanesthesiology?

Dr. Hudson: I am tremendously excited that we have started to ask questions about how changing the activity in networks produces unconsciousness, and how changes in activity patterns occur during recovery of consciousness. There is some interesting work to suggest that the parietal lobe is particularly important for conscious experience, but quite a bit of evidence implicates the frontal lobe as well. It may prove that changes in how these areas interact could be the final common pathway by which molecularly diverse anesthetics disrupt consciousness. Early attempts at quantifying those interactions haven’t quite worked to correlate with unconsciousness, but several groups are exploring this, and it is an exciting time to be working on this question.

Dr. Koerner: Can you tell us about your research and how the William Young Award supported your success?

Dr. Hudson: My own work has focused on using anesthetics as a tool to vary the level of consciousness and then study the changes in the nervous system activity that result. Anesthetics are incredible tools that let us reversibly interrupt consciousness in a structurally normal brain, and then we can watch the recovery of consciousness in real time as the drug clears.

My lab started with a focus on the dynamics of brain activity during anesthesia, that is, how brain activity patterns transition among each other during periods of consciousness. The brain will occasionally transition, seemingly at random, between a few patterns that are compatible with a given level of anesthetic; these transitions are relatively rare as brain activity patterns seem to be sticky. This stickiness means that brain states have their own intrinsic mixing time, so even if you are at pharmacologic equilibrium your brain state might not have finished arriving at equilibrium. Amazingly, if you combine this notion of sticky brain states with the intuition that there are more unconscious brain states than conscious brain states, you can predict all of the known features of ‘neural inertia’, the difference in dose response between induction and emergence. This also means that we have left one key factor out of our definition of MAC, namely the amount of time that you have been at that anesthetic concentration.

The neuronal dynamics we study result from shifts between allowable brain activity patterns. In some sense the allowable activity patterns are determined by the coupling constants between neurons, so the fact that some activity patterns are only seen at a few levels of anesthetic tell us that the coupling between neurons is changing. The question is how. To answer this, we have started doing calcium imaging of different neurons that play distinct roles within the cortical circuit: pyramidal cells in layers two-three or layer five, and inhibitory interneurons. The William Young Award has let us buy some essential equipment to pursue an interesting dissociation between layer two-three neurons and layer five neurons that initially looked like an artifact in the background, but turned out to be out of plane layer five neurons firing in synchrony. We have almost finished characterizing what is going on, so hopefully that story will be in print soon.

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