Abstract
In honor of Dr. James S. Hyde's contributions to the field of functional magnetic resonance imaging (fMRI) and resting-state functional connectivity magnetic resonance imaging (rs-fcMRI), we, the current and former graduate students, postdoctoral researchers, faculty colleagues, and academic friends, dedicate this two-issue special Festschrift publication series to him. We begin this publication with some personal reflections about Jim's impact on our scientific careers and the broader academic discipline of functional neuroimaging. More personal reflections will be included in the second issue of this Festschrift series.
Jim Hyde's Former Graduate Students
I did my PhD under Dr. Hyde from 1987–1991 and was on the junior faculty at the Medical College of Wisconsin (MCW) until 1994. The style of leadership that Dr. Hyde brought to the department, and the atmosphere generated by that style, were eclectic and unique, as I would understand much later. At the time it was both intimidating and wildly encouraging. He would lurk the halls, larger than life, slowly pacing with coffee cup in hand, delivering strange stares, tangential comments with hidden nuggets, devilish smiles, and awkward silences. From all this, the message was simple, just keep thinking. Question everything, question everybody, start from first principles, and question yourself twice. I learned that the big picture is critical, as is every detail underneath. I learned that being wrong is good, that if you are never wrong you are too careful, and that mistakes are to be understood, not defended. Dr. Hyde afforded the luxury to think outside the box by simply failing to acknowledge that a box even exists. To this day I don't know whether his approach to science and teaching is just in his DNA or some carefully crafted synthesis, but for me it created a formative experience for which I will always be grateful.
Eric Wong, PhD, MD
MCW Biophysics PhD, 1991
Professor and Associate Director for Imaging Hardware
Center for Functional MRI
Department of Radiology
University of California, San Diego
The impact of Jim Hyde
In the Introduction of my contribution to this Brain Connectivity special issue, I mention that Jim Hyde had an impact on me right from the start. Sitting in his office for the first time, the interview felt more like a recruitment for a Shackleton voyage to Antarctica or a Teddy Roosevelt big game hunt in Africa. Simmering beneath his confident, visceral, laconic presence is a deep passion and excitement for what he does. He's on an adventure—a hunt—and we had better pay attention and get serious if we want to come along. All of his students have been imbued to some degree with this passion and boldness. At that interview he stated: “There's a wealth of information in the signal, and we're in the business of extracting it.” I was hooked.
Jim has great skill in uncovering rich scientific opportunities—repeatedly crafting novel and far reaching ideas—from the loop gap resonator to daily advice to his students, all the way to his stunning and prolific grant success. He prefers thinking in first principles—helping him to build creative links across disparate concepts and otherwise tenuously related disciplines. The Biophysics Department (previously Research Institute) is like no other. It was built around his two areas of expertise, electron spin resonance (ESR) and MRI, and it has thrived on the links and collaborations that have been made. Equipped with a world class machine shop and coil lab, and offering resources, space, collaborative expertise, time, and encouragement to all who work there, it is the perfect incubator for leaps in creative advancement—like fMRI with a programmed-from-scratch echo planar imaging (EPI) sequence and a local head gradient coil made out of sewer pipe, wire, and epoxy; or resting state fMRI using a reference vector taken from the time series of a subject not performing a task!
He set the stage on all levels in creating the right physical, scientific, and social atmosphere. His reputation and experience provided wonderful connections to his old friends like Seiji Ogawa, as well as companies down the road like GE and Medical Advances—all playing essential roles at various stages. So, aside from helping all of us do our best work, an aspect of his powerful influence that has stayed with me has been his simultaneously respectful and irreverent drive. He deeply respects scientific rigor and solid past work—drawing from it constantly. However, he's having the most fun when he's unapologetically reinventing, in his own way, what's possible.
Peter A. Bandettini, PhD
MCW Biophysics PhD, 1994
Chief
Section on Functional Imaging Methods
National Institute of Mental Health (NIMH/NIH)
Editor-in-Chief, Neuroimage
In celebrating Dr. Hyde's distinguished scientific career, I feel extremely lucky to have been one of his trainees as a graduate student. His remarkable insight and scientific vision have been well acknowledged in the field. His light-touch training style, encouraging independence and free thinking, allowing me to explore my scientific interests, could only be appreciated as his student and even more so as I continue on my career. My first-year summer project was to design and construct a high-efficiency local gradient coil to perform rat fMRI on a Bruker 3 Tesla human scanner. With tremendous help from his two meticulous staff members, Dick Johnson and Rich Scherr, we completed the project in 2 years. This was a unique opportunity, as I realized later on, very few laboratories have the resources and support to conduct this type of research. In the meantime, he also patiently trained me in MR spin physics and imaging sequence development. With the gradient coil, radio frequency (RF) coils, and the multishot partial k-space EPI sequence we developed, we were able to push fMRI resolution to cortical laminar level in rat whisker barrel cortex.
With the help of Sachin Patel, a graduate student in the Department of Pharmacology, we also mapped c-fos expression as a marker of neuronal activity. This training combined MR physics, imaging technology, and neuroscience, and continues to shape my research now. As I recall vividly, at one point, I asked for his advice on my PhD dissertation topic. After a long pause, as many of his students might have encountered, he suggested resting state MRI in a rat model. I did not end up doing this topic for dissertation, but I was amazed for quite some time that he would let me go with it—more evidence of the academic freedom his students enjoy.
Hanbing Lu, PhD
MCW Biophysics PhD, 2003
Research Scientist
Neuroimaging Research Branch
National Institute on Drug Abuse (NIDA/NIH)
My academic career could not have started without Dr. James S. Hyde, who not only served as my mentor but also encouraged and supported me over those early years. Many years ago I came into the biophysics research field as a surgeon. I still remember the first day Dr. Hyde and I met in his office, where we had a long discussion on animal fMRI research. I was deeply impressed by his insight and enthusiasm as well as his knowledge of basic science. It was from that moment on I told myself that I wanted to learn from him and become his student, although as a beginner, I did not realize his influence in biophysics research at the time.
The more I know about biophysics research, the more I appreciate the chance I got to be Dr. Hyde's student and learn from him every day. His name regularly appears in the most important literatures in the field, and his ground-breaking work on resting state functional connectivity is still one of the most significant findings in biophysics and neuroscience research.
I am so grateful that Dr. James S. Hyde offered me so many interesting research projects to work on, transformed me into a scientist, and I have tried my best to be a great researcher. His insight, vision, and enthusiasm for science have guided me through my graduate study and will keep on influencing my career. I am so lucky to have been his graduate student, and Dr. James S. Hyde is truly the best mentor I have ever had.
Rupeng Li, PhD, MD
MCW Biophysics PhD, 2012
Staff Scientist
Department of Biophysics
Medical College of Wisconsin
Jim Hyde's Current and Former Medical College of Wisconsin Colleagues
Jim Hyde is responsible for one of the most significant turns in my professional career. In 1991, I was a professor of psychiatry at the Medical College of Wisconsin. My research at the time incorporated regional cerebral blood flow (CBF) autoradiography to understand the neurobiological mechanisms of abused drugs. One day, a second year graduate student came to my office to discuss a recent finding he and another graduate student made using some type of MRI technology that I had never heard about. He claimed that when he tapped his fingers, this MR signal increased and it was due to an increase in blood oxygenation. I quickly “corrected” him, stating that the prevailing dogma was that the brain used oxidative metabolism of glucose, so when a region was more active, the amount of oxygen had to go down. Since he was a graduate student and I a professor, he left my office quietly but soon returned in a day or so politely saying his biophysical modeling and the direction of the signal meant I was the one who was mistaken. My next step of course was to ask to meet his major professor whom, I was sure, I would quickly show the light of their error. So Peter Bandettini introduced me to Jim Hyde, who was the director of the MCW Biophysics Institute and also the mentor to Eric Wong, the “other” student (and many others, I was soon to learn).
Thus began one of the most scientifically important turns in my career. Jim soon straightened out the neophyte imager while trying to cram an introduction to MR physics into me virtually overnight. He took no prisoners and threw me into the deep end. But fortunately for me, he and his eclectic lab (perhaps an understatement when considering Andrzej Jesmanowicz) were always there to throw me the lifeline I often needed. Jim was generous with his time and impressively open with his facility. He was encouraging and most happy when outsiders like me would hang around the Biophysics Institute. When I tried (and mostly failed) to do some of the earliest rat fMRI experiments on the then new Bruker 60 cm 3T at MCW, I was impressed at how generous he was with his equipment and the time of his staff. He insisted that I need not ask to borrow a coil or ask his permission for his engineer to make coil modifications, and made me feel like a member of the family. There was never a question about money or access. He was proudest when his “kids” were successful. He loved having all of us employ the MCW green on our early International Society for Magnetic Resonance in Medicine (ISMRM) abstracts.
But I think I learned the most from Jim when we were writing our fMRI program project grant (PPG), which was funded by the National Institute of Mental Health (NIMH) from 1994–1999, and then renewed for a second 5 years. Even though I was already a well-funded investigator, I learned more from Jim about how to think through and design experiments and then write a grant than I could imagine. I also learned from him how to put together a large, complex document. Jim did not use a computer and his wife was the principal word processor. We were running late on our submission deadline and all the PIs were busy writing in their respective offices. Jim called and wanted my section, which was, like everyone's, still a work in progress. I promised it shortly and hung up. He called again a few minutes later and the scenario repeated. A few minutes later I looked up from my keyboard and Jim was sitting in the corner of my office—quietly, not saying anything. But no words were needed. He wanted what he wanted and when he wanted it. Alas, he didn't leave the office until he had the pages he needed so he could move on with the application.
Jim's greatest lasting legacy on me was how to run a lab and integrate scientists from across disciplines. He had a vision, even early on, that for this nascent field to be successful one had to embrace all flavors of scientists, from MR physicists to engineers, from cognitive neuroscientists to blood flow regulatory physiologists. This has proven most prescient as neuroimaging has evolved to be a bastion of multidisciplinary investigation. Jim's fingerprints are not only all over the field but can be found all over those who have passed through my lab.
Thank you, Jim.
Elliot Stein, PhD
Chief
Neuroimaging Research Branch
National Institute on Drug Abuse (NIDA-IRP)
I count myself incredibly fortunate to have had the opportunity to pursue my graduate studies and get my PhD at the Biophysics Research Program at the Medical College of Wisconsin, which at that time was headed by Dr. James Hyde. I first met Dr. Hyde, as we graduate students typically called him, in 1994 only a few years after functional MRI was first discovered. He gave students a lot of freedom to pursue whatever research they were interested in and provided amazing opportunities to carry out this research, such as free scan time (after hours) and access to the nuts and bolts of an MRI scanner. I was most impressed with his seemingly endless list of great ideas. It was typical of Dr. Hyde to come into the office where we graduate students were working, sit down, and then start to explain one of his ideas and suggest that we pursue this idea. This happened multiple times a week, and while at first I felt overwhelmed by the number of ideas he suggested I try, I ended up latching on to the idea that most sparked my curiosity. This topic, investigating the effect of task-correlated motion, eventually became my PhD thesis. I suspect that perhaps this was his intention all along—to throw multiple great ideas at me to see which I run with.
I also recall from my very early graduate school days the intense interest that Dr. Hyde had for the low-frequency oscillations in the fMRI signal, which are the foundation for what is now known as resting-state functional connectivity. He would show these findings, on which his student Bharat Biswal was working, to every visitor coming through the lab. It is amazing to see how far this area of research has come, and the intense interest and enthusiasm it has generated among physicists, neuroscientists, and clinicians. I am also truly inspired by Dr. Hyde's long successful career and his continuing contributions to the field. Only a month ago I was at one of his student's PhD thesis defenses, and Dr. Hyde's insights and comments during the defense were at the same brilliant level as I recall from my graduate school days. I am incredibly grateful and honored to have had the opportunity to know, study with, and work with Dr. Jim Hyde.
Rasmus Birn, PhD
MCW Biophysics PhD, 1999
Assistant Professor
Department of Psychiatry
University of Wisconsin–Madison
One of the most remarkable features of Dr. Hyde's professional work is its originality. I met Dr. Hyde in the early 1990s when he and then graduate student Bharat Biswal were doing their functional imaging work that led to the discovery of resting state functional connectivity. I joined the faculty of MCW in 1989 and was working on the autoregulation of CBF in a rat model using a recently acquired new device laser Doppler flowmeter. What we saw was that under certain hypotensive conditions, CBF began to spontaneously fluctuate across cerebral cortex.
With colleagues Richard Roman and David Harder, we published an original article on spontaneous flow oscillations. It was then Dr. Hyde found me exclaiming that surprisingly someone happened to be working on a related physiological foundation in at his own institution! He immediately saw the connection between our animal study and their discovery of spontaneous physiological fluctuations in BOLD signal in specific brain areas “functionally connected” in human subjects. After his first seminal article first-authored by Bharat Biswal in 1995 on the low-frequency fluctuations, we published a collaborative article demonstrating that the effect of hypercapnia was similar in the two models, rodent and animal. From that point on, we have continued an ongoing collaboration that has resulted in many more original publications.
Over nearly two decades, it has been a privilege to work with Dr. Hyde in various projects. Whether in formal meetings or just over our usual cafeteria lunch, we have pondered together many new ideas that could be experimentally tested. Dr. Hyde has been an inexhaustible source of knowledge, brilliance, and inspiration for all of us.
Anthony Hudetz, DBM, PhD
Professor
Departments of Anesthesiology, Physiology and Biophysics
Medical College of Wisconsin
We've now begun the third decade of research using magnetic resonance imaging as a tool for probing the functions of the human brain. Probably no other person is more responsible for ushering in this era than James S. Hyde, PhD. Jim is among a small group of MR physicists capable of creating disrupting MR technologies that lead to critical insights into the workings of our most complex organ, the brain. As director of the biophysics program at the Medical College of Wisconsin, Jim mentored many of our current leaders in functional neuroimaging. Several key innovations and discoveries, which we now take for granted, came from these teacher–student interactions.
In the early 1990s, Jim mentored two talented graduate students, Peter Bandettini and Eric Wong. This team built an insertable gradient and RF coil that enabled one of the first task-activated fMRI studies conducted in humans using the BOLD effect. Along with nearly simultaneous publications by the University of Minnesota and Massachusetts General Hospital, the MCW group brought forth one of the most important methodologies for understanding the human brain in the late 20th century.
These teacher–student interactions resulted in a similar groundbreaking investigation in the mid-1990s, when Jim oversaw the work of his graduate student, Bharat Biswal. Together they published the first resting state functional MRI study using BOLD imaging. Today this technique has gained widespread acceptance as a tool for probing the ways in which distant brain regions communicate with each other. This important discovery has led to support of large-scale scientific studies known today as the human connectome.
Of course, Jim also created innovations with his colleagues. Along with Andrej Jesmanowicz, Jim was the first to demonstrate real-time functional MRI, the near instantaneous display of brain activity based on BOLD imaging. This innovation has sparked several therapeutic approaches designed to manage pain and treat neurological and psychiatric disorders.
As a colleague of Jim's, I have always been impressed by his ability to include persons from diverse professional backgrounds into his sphere. He is quick to understand the ramifications of his innovations for the field of neuroscience and is relentless in recruiting talent to assist him in exploiting his scientific innovations. I, for one, am indebted to Jim for his foresight, generosity, encouragement, and mentorship.
Stephen M. Rao, PhD
Director
Schey Center for Cognitive Neuroimaging
Cleveland Clinic
Jim Hyde's Friends and Colleagues Outside of the Medical College of Wisconsin
Personal reflections on Jim Hyde, resonant scientist
I first met Jim Hyde in 1989, I think, after I had been working as a visiting scientist at National Institutes of Health (NIH) for about a year. At that time I was deeply engaged in designing and building gradient coils, for the purpose of enabling echo planar imaging and diffusion-weighted MRI, to be performed on the NIH MRI scanners of the time. These were 2T and 4.7 T animal scanners, and 1.5 T human scanners. On the 2T scanner, in 1989, I was able to demonstrate diffusion-weighted EPI for the first time in animal brain, and by 1990 I could do the same at 1.5 T with the human brain. Jim heard about my work, possibly from my presentations at the Society for Magnetic Resonance in Medicine (SMRM) meeting in 1988, and invited me to Milwaukee to give the first of several talks in the following two years to his group of young, smart and enthusiastic PhD students, which included Eric Wong and Peter Bandettini. From the very first, I found it a delight to interact with Jim. He grasped new concepts so fast, and greeted them with such enthusiasm. He was so aware, from the earliest days, of the vital importance of getting the hardware right, and the deep relevance of good physics to the solution of the hardware problems.
It was at the 1990 SMRM annual meeting in New York, I recall, when Jim first suggested that I move to Milwaukee to join him at the Medical College of Wisconsin. We worked on this possibility for about a year. I was deeply flattered and greatly intrigued by the opportunity to develop my own program at a senior level, and to interact on a day-to-day basis with the amazing group of young scientists that Jim had assembled and inspired. But the installation of a prototype 4T scanner at NIH, and my move to Bob Balaban's laboratory of cardiac energetics at National Heart, Lung, and Blood Institute (NHLBI), which gave me full access to this huge scanner, made me feel it was not the right time to start again in a new city. I felt real regret, however, because the chance to work more closely with Jim was very attractive.
Since that time, he has always been great to talk science with. We have touched base at countless conferences, always with the same sense of excitement and wonder of scientific discovery. But Jim is also well rounded, genial, deeply rooted in the northern Midwest, and firmly linked with its spirit of place. For me he has always been a role model in exemplifying the value of being tuned in to ones' social and natural environment. There are very few other scientists whom I have known personally that I would comfortably describe by the word “great.”
Robert Turner, PhD
Director
Department of Neurophysics
Max Planck Institute for Human Cognitive and Brain Sciences
Leipzig
Germany
I've had the honor of meeting many brilliant scientists during my career, including four Nobel laureates. I've had conversations with Drs. Georges Charpak, Murray Gell-Mann, Klaus Von Klitzing, and Paul Lauterbur. These were not casual meetings with these notable scientists, they were, for various reasons (a beer with Charpak at a ski resort, dinner with Gell-Mann, etc.) in-depth conversations. I've also had the honor of having had many conversations with Dr. James Hyde. I can say without hesitation that Jim is one of the most visionary of the many scientists that I have ever met.
I first met Jim in the spring of 1995. I was very new to the field at that time. I was a post-doc at UW-Madison. There was a close relationship between the MR research programs at MCW and UW-Madison at that time, and I benefit to this day from that closeness.
Jim's impact on my career stems from the 1995 inaugural human brain mapping meeting. I had been studying the BOLD response to drug challenges in monkeys and could not understand the results I was getting with the control data (essentially, monkeys in the resting state). At that meeting, I saw Jim present for the first time his and Bharat Biswal's findings regarding resting state functional connectivity. It completely explained my findings. I immediately switched to working in humans and eventually published an article confirming and extending their findings. Had it not been for Jim and his colleagues at MCW recognizing what they saw for what they really were, my career would be quite different. It took many years for most people to finally recognize what Jim saw immediately. As everybody now knows, resting state functional connectivity is (arguably) the predominant functional neuroimaging method used by neuroscience researchers.
Jim and I became friends while I was working on that article. Despite several attempts, Jim and I have not had the opportunity to collaborate directly on a project. Still, I consider him to be a valued mentor. I have had many insightful conversations with him over the years and have enjoyed his company and conversation at many meetings. It is a great honor for me to contribute an article on resting state functional connectivity to an issue dedicated in his honor.
Mark J. Lowe, PhD
Director, High Field MRI
Cleveland Clinic