Welcome to the Neuroscience Initiative Website. We deeply appreciate everyone who is on the frontline of research. Come check in periodically to see spotlights on various faculty working in neuroscience.
Jacob George, PhD
By Samantha Weeks
Dr. Jacob A. George, PhD, is an Assistant Professor in the Department of Electrical & Computer Engineering and the Division of Physical Medicine & Rehabilitation. He also serves as the director of the Utah NeuroRobotics Lab and is a foundational researcher for the new Craig H. Neilsen Rehabilitation Hospital. He is affiliated with the Utah Robotics Center and Center for Neural Interfaces, and has an adjunct appointment in the Department of Biomedical Engineering.
Dr. George received his undergraduate degree from The University of Texas at Austin with Highest Honors and was the sole recipient of the Biomedical Engineering Student Leadership Award for his contributions to his department as President of the Biomedical Engineering Honor Society. He went on to receive an MS and PhD in Biomedical Engineering from the University of Utah in 2018 and 2020, respectively. As a graduate student at the U, he served as the Co-President of the Graduate Student Advisory Committee and Inaugural President of the IEEE Engineering Medicine and Biology Student Chapter.
Throughout his training, he has received numerous scholarships and fellowships, including the Don B. Olsen Graduate Fellowship in 2016, a National Science Foundation Graduate Research Fellowship in 2017, and an NIH TL1 postdoctoral fellowship in 2020. He has also been the recipient of two Society for Neuroscience Awards, received an IEEE Best Paper Award, was a finalist for the Ripple Innovation in Research and Promising Young Investigator Award, and was awarded the Association of Clinical and Translational Sciences Outstanding Postdoc Award. Most notably, in 2020, he was awarded the NIH Director’s Early Independence Award (DP5) to establish his own independent research lab - the Utah NeuroRobotics Lab. The NIH Director’s Early Independence Award is given to only ~10 individuals each year, and his award is the first in the field of Physical Medicine & Rehabilitation and the first in the Intermountain West region.
This award provides his lab $1.8M over the next five years to develop more intuitive and dexterous control algorithms for upper-limb exoskeletons to assist and rehabilitate stroke patients. Over the last year, the 1st year on the project, the investigative team integrated various technologies and developed novel algorithms for extracting motor intent from paretic limbs. Now that on-campus and human-subject research activities are resuming, they are recruiting patients to validate the new control strategies and technologies developed.
They are also recruiting patients to help evaluate new neuromuscular and sensory diagnostics and new rehabilitative tools. For example, they have been developing new ways to non-invasively stimulate the arm nerves to reanimate paretic limbs after a stroke or spinal cord injury. In addition, they are working on new, more quantitative, diagnostic measures for fine hand dexterity or neuromuscular recovery, as well as developing intelligent “self-aware” bionic arms that can function autonomously and work in synergy with a human user. Ultimately, Dr. George envisions a world in which bionic devices can be used to restore lost functionality, and potentially enhance dexterity beyond normal capabilities. They are already making rapid progress: Luke Skywalker’s bionic arm used to be science fiction, but is now very much becoming a reality.
These advances have not come without their own set of challenges. Starting a lab in the middle of COVID-19 was not an easy task. Dr. George and his team take great pride in their ability to test their technology with the end user (e.g., stroke patients, amputees, etc.), a process which is rare in the field and uniquely enabled by their lab being located in the new Craig H. Neilsen Rehabilitation Hospital. During the peak of COVID-19, they were not able to test devices with patients, and that certainly slowed progress. While working remotely, they adjusted to analyzing previously collected datasets, developing new algorithms, and testing technology on the family & friends with whom they were isolated. They are now back up and running, and currently looking for new participants!
Dr. George’s research is extremely interdisciplinary. His lab consists of people from neurosurgery, physical medicine & rehabilitation, electrical engineering, computer engineering, computer science, neuroscience, biomedical engineering, mechanical engineering, and even civil engineering. His lab works at the intersection of brain-computer interfaces, rehabilitation robotics and artificial intelligence. In specific, they use bioinspired artificial intelligence to link brain-computer interfaces with assistive and rehabilitative robotics.
Their 2019 publication in Science Robotics has received over 100 citations in under two years and was featured in over 400 unique news articles. Those news articles netted over 450.4 million views and resulted in $4.5 million in advertising for the University of Utah. The publication currently has an AltMetric of 893 (https://robotics.altmetric.com/details/63985487), which puts it in the top 5% of all research papers and ranks within the top 10 papers of all time from Science Robotics.
In this work, they implanted a neural interface into the residual arm nerves of a human amputee to provide an intuitive bi-directional link between their brain and a multi-articulate bionic arm. When the participant thought about moving their hand, they decoded information from their nervous system into dexterous movements of the bionic arm. And when the bionic arm made contact with objects, pressure sensors from the hand were used to trigger stimulation of the arm nerves which evoked a natural-feeling sense of touch originating from their missing hand. Using this system, they showed that sensory feedback is critical for fine hand dexterity (e.g., allowing individuals to manipulate fragile objects without breaking them) and that sensory feedback enables haptic perception (e.g., the ability to discriminate objects based on size or compliance). But most importantly, they showed that by mimicking the natural spatiotemporal activation patterns of nerve, the artificial sensory feedback they provided became more intuitive and useful. That is, at a broader level, if you communicate with the brain in the brain’s natural language, the neural interface becomes more intuitive and useful to the individual. This idea of mimicking the natural language of the nervous system has broad implications for a variety of neural interfaces that could be used to treat a variety of different neurological impairments (e.g., reanimating paralyzed limbs, blocking pain, regulating autonomic function, etc.).
Growing up in a military family and regularly moving to new cities has taught Dr. George how to adapt to new environments and connect with people from diverse backgrounds. Research is the perfect fit as he can combine his love of connecting with diverse people while also using his research to help others. He welcomes the chance to partner with companies and researchers who have developed new brain-computer interfaces, robotic devices, or artificial intelligence algorithms. For example, his team previously collaborated with people and companies that have developed new electrodes, where their role was to test the new devices with human subjects in exciting new applications. They have also collaborated with companies that have developed new robotic devices, where their role was to develop a more intuitive approach to dexterous control via a brain-computer interface. And lastly, they’ve also worked with groups that have developed new algorithms, that they can modify and test as a new tool to link the nervous system with robotic devices.
Sophie Caron, PhD
By Samantha Weeks
Sophie Caron, PhD is an Assistant Professor in the School of Biological Sciences at the University of Utah.
Dr. Caron grew up in Saint-Blaise-sur-Richelieu, a small farming village in the South of Quebec. After studying in Montreal, she moved to New York City for her PhD and post-doctoral training. As an undergraduate, she studied biochemistry, before transitioning to developmental genetics as a PhD student, and then neuroscience for post-doctoral training. Her diverse educational and training background have instilled in her a belief in system wide, cross-disciplinary approaches. Together with members of her laboratory and collaborators, she works to identify questions and subsequently find answers by using concepts and techniques rooted in neuroscience, developmental biology, evolutionary biology, genetics, and mathematics.
Over the course of Dr. Caron’s career, she has learned to make the best out of every opportunity, and to take full advantage of her immediate surroundings. After joining the University of Utah School of Biological Sciences, she became interested in using evolution as a tool to understand how the brain represents sensory information efficiently. With the help of the strong community of evolutionary biologists and geneticists from across campus, she began to think about ways to include evolutionary biology in various approaches. Being able to discuss these burgeoning ideas with her colleagues helped her to crystallize these ideas into testable hypotheses and rewarding research endeavors.
Recently a manuscript that looks at how different connectivity patterns shape representation space in the brain was deposited on bioRxiv. Though theoretical, this work has been inspiring for her to imagine "what could be?" using a computational model of the brain. It is much easier to disrupt or create connectivity patterns in silico than it is in vivo. This study investigated how different brain functions come about the way neurons connect to each other. Conclusions derived from this study enable her and her lab to understand our experimental system much better.
Dr. Caron was recently awarded an NSF CAREER award, which recognizes a strong commitment to research, as well as teaching and outreach, both of which she is passionate about. This career award funded a project that was initiated by a graduate student (Chelsea Gosney) in her lab and a former undergraduate student, turned lab manager, and soon to be graduate student at CalTech (Hayley Smihula). Ms. Gosney and Ms. Smihula found that the brain of most Drosophila species scale relatively to their body size with the notable exception of Drosophila pseudoobscura. Working together, they are planning to develop Drosophila pseudoobscura as a model to study "encephalization", the phenomenon brains gained in size relatively to body ratio. Because the Drosophila brain is numerically simple and amenable to different techniques to label neurons, record their activity and map their connection, the team believes they will be able to find out how and why brains can expand by studying big-brained flies such as Drosophila pseudoobscura.
Looking at Dr. Caron’s projects, it is obvious that she takes interest in the people around her, and grows from their strengths and knowledge. There is no doubt that those around her, in turn, learn and grow from her strengths and knowledge. She is always looking for engaging collaborators who share common goals and interests.
Deborah A. Bilder, MD
By Samantha Weeks
Deborah A. Bilder, MD, is an Associate Professor in the Department of Psychiatry in the Division of Child & Adolescent Psychiatry and adjunct Associate Professor in the Departments of Pediatrics and Educational Psychology. She is a clinical and research expert in autism and is the Co-PI for the Utah site of the Centers for Disease Control and Prevention’s Autism and Developmental Disabilities Monitoring Network.
Dr. Bilder grew up in Wellsboro, a small town in north central Pennsylvania, where her mother was the first pediatrician in Tioga County. In this important service role, Dr. Bilder’s mother instilled in her a sense of responsibility to serve and care for others.
Dr. Bilder received her BA from Wake Forest University, and MD from Vanderbilt University School of Medicine. During medical school, she frequently volunteered at homeless shelters and soup kitchens, experiences that inspired her to become a psychiatrist. However, during her 3rd year medical school rotations, she also fell in love with pediatrics. Upon hearing of the triple board residency program at the University of Utah, she knew it was the program for her: it was Utah or bust! She completed the triple board residency program (Pediatrics, General Psychiatry, Child & Adolescent Psychiatry) in 2003 and maintains board certification in all three specialties.
Following residency, Dr. Bilder’s clinical time was split between general outpatient child psychiatry and a new clinic for patients with neurodevelopmental disabilities. Her pediatric mentor invited her to participate in the Utah Regional Leadership Education in Neurodevelopmental and Related Disabilities (URLEND) certification program. Through her year in URLEND, she found her passion for working with this patient population. She came to realize her leadership responsibilities as a provider and what the future could be for the developmental disabilities community, and in particular, the autism community.
Flexing her leadership skills, Dr. Bilder helped grow the Neurobehavior HOME program, a Medicaid-funded sub-specialty medical home program for individuals throughout the lifespan with neurodevelopmental disabilities. Her research career has spanned many projects, but she credits a particular paper, “Excess Mortality and Causes of Death in Autism Spectrum Disorders: A Follow up of the 1980s Utah/UCLA Autism Epidemiologic Study,” as helping to put her work on the map. The Interagency Autism Coordinating Committee, within the Department of Health and Human Services, selected this paper as part of the Top 20 Advances in Science in 2012. One of Dr. Bilder’s subsequent papers, “Maternal prenatal weight gain and autism spectrum disorders” shifted her field’s focus towards prenatal metabolic processes and autism risk.
Speaking of the intersection of her clinical and research work she said, “Being a researcher really informed a lot of what I was able to do clinically, and yet the patients I’d see every day really informed the questions I would bring to the research setting.” Dr. Bilder knows there is more work to do for the autism community. “I’m passionate about raising the standard of care for this population.” She looks forward to working with community leaders, whom she considers to be critical partners in advancing autism care, to address questions such as: Where is the prevalence of autism going? Where are the discrepancies? Are there ethnic communities or socioeconomics classes where autism is not being recognized? How can we shape our intervention, our recognition efforts, and our treatment efforts in the community to ensure everyone has a fair shot?
To improve the chances that everyone has a fair shot, Dr. Bilder created a tool called “Sources of Distress”. This tool uses branching logic to provide a differential diagnosis for patients. Since a targeted diagnosis can lead to targeted care, this tool is now the foundation of each of her clinical consults. Dr. Bilder is currently partnering with TVC to marry the “Sources of Distress” tool with the Electronic Medical Records (EMR). In this next iteration, patient caregivers will complete the “Sources of Distress” survey prior to a clinic visit. The results will be fed to the EMR, informing providers about the patient’s status, and providing specific treatment targets for intervention. Additionally, she is developing treatment algorithms that when interfacing with the EMR, would recommend a plan of action based on “Sources of Distress” and additional provider input. Provider notes will populate with pertinent history and the medical decision-making process that supports the diagnosis and treatment plan. This tool will enable providers to better care for this population.
It is clear that Dr. Bilder has had continuous impact among the autism and broader neurodevelopmental disease communities. For her, “It’s not just about a job. It’s about having a career that has impact among those we serve.”
Kevin Duff, PhD
by Kyle Wheeler
There are a host of potential lemons that can sour the work of a research scientist. But Dr. Kevin Duff—a neuropsychologist at the University of Utah—considers himself someone who has taken a proverbial lemon and continues to make lemonade.
For scientists and clinicians using cognitive assessments, practice effect is a thing to be minimized. Concerning practice effects, the APA notes that, “performance on the variable of interest may improve simply from repeating the activity rather than from any study manipulation imposed by the researcher.”
While practice effect can be a barrier to longitudinal assessment, Dr. Duff has focused his research on leveraging practice effect as a useful marker. Rather than noise that interferes with findings, Dr. Duff is turning practice effect into the method of prediction.
Like any specialist, there is a journey that brought Dr. Duff to this point of building a predictive use out of practice effects. His interest in psychology and ultimately neurology budded at a young age. He notes psychology resonated with him in a high school class and continued to resonate through undergraduate studies at University of Massachusetts-Dartmouth.
Subsequently, that interest found more depth as Dr. Duff continued his studies and received an MA in Psychology at the University of Northern Colorado, followed by a PhD in Clinical Psychology from the State University of New York at Albany. Dr. Duff completed an internship at the Southern Arizona Healthcare System and his post-doctoral fellowship at the University of Oklahoma Health Science Center.
Dr. Duff then joined the Psychiatry Department at the University of Iowa, where he was launched into cognitive assessment as he worked with Dr. Jane Paulsen, who ran a center of excellence for Huntington’s Disease. Huntington’s Disease shows up with difficulties in motor function, psychiatric function, and cognitive function. Since it is a disease with a known genetic origin, it is possible to observe early markers of the disease, manifesting opportunities for continued assessment.
In working with Dr. Paulsen, their driving research question was which area of symptoms starts to show up first: motor, psychiatric, or cognitive?
Dr. Duff was tasked to focus on psychiatric symptoms and assessment. He notes that early on, Huntington’s Disease is often misdiagnosed as depression, anxiety, or even schizophrenia. Additionally, “a lot of patients lack insight into their own symptoms.”
When asked about the implications studying Huntington’s Disease may have beyond the disease itself, Dr. Duff answered: “One of the unique things about Huntington’s Disease is that we know where the genetic defect is, whereas we don’t know that with a lot of other diseases. Dr. Paulsen and a lot of other people who focus on Huntington’s Disease would make the argument that what we learn from Huntington’s Disease we can apply to things that are close to Huntington’s Disease, like Parkinson’s Disease.
“But we can also apply it to diseases that are more different, like Alzheimer’s Disease or Frontal-Temporal Dementia or ALS. We think that the lessons that we learn from this genetic disease can feed into what we know about perhaps figuring out the genetic components of some other neurological diseases.”
His research into Huntington’s Disease has been compelling and has practical application in understanding Huntington’s Disease and beyond. But it is also evident that Dr. Duff is invested in the human side of the research he’s worked on.
Of his time studying Huntington’s Disease at the University of Iowa, Dr. Duff reflected that it was intellectually challenging, but that to see the human side of it was tremendously fulfilling.
With the warmth of a quality clinician and the intellectual depth of a scientist, Dr. Duff has continued his career with a focus on practice effects. That area of focus has spanned from his time in Iowa to his work at the University of Utah that began over a decade ago. Dr. Duff suggested that this area of focus has been his effort to turn those proverbial research lemons into lemonade.
He goes on to share that, “many people try to study practice effects so that they can minimize or negate them. A lot of my research is focused on using that practice effect as a measure of brain health or plasticity.
“Whenever somebody shows that practice effect, it’s actually a good thing. What we’ve noticed is that practice effects are smaller in patients with brain disease. So, we’ve been using this decreased practice effect as a marker of how severe their disease is.”
Not only is Dr. Duff’s work leveraging practice effects as an indicator, but he has worked to turn it into a predictor of where a patient will be in the future. To this point, Dr. Duff notes, “I’ll bring patients in to evaluate their memory and other thinking abilities, bring them back a week later and repeat the exact same tests. Over one week, I can get a sense of where someone’s going to be a year down the road.”
It is an intriguing line of study to take an effect that apparently needs to be minimized and turn it into a useful tool. While the scientific implications are profound, it is impossible to forget when speaking to Dr. Duff that the patients are always the focus. Maximizing predictive tools is a win, but being able to better help people is clearly a fulfilling endeavor for Dr. Duff.
Adrian Rothenfluh, PhD, MSc
by Kyle Wheeler
What do you get when a fly and a neurobiologist/geneticist walk into a bar? The answer may not be the punchline of a joke, but a reality that can teach us a lot about our brains. When it comes to intoxicated drosophila, Adrian Rothenfluh PhD, MSc is more the designated driver, looking for answers embedded within the brains of the drunk flies in his lab.
As noted in his research statement: "Dr. Rothenfluh's research focuses on the genetics of psychiatric disorders, especially addiction. His lab uses Drosophila to model various neuropsychiatric conditions and to investigate the molecular, signaling, and neuronal mechanisms that mediate behavior. His lab has a continued commitment to translate his findings to human studies."
Working at a unique intersection of human genetics and neurobiology with findings that have a translational impact on our understanding of psychiatry, Dr. Rothenfluh came to the University of Utah with his "better-half, looking for a place with a trajectory," they liked. At the University of Utah, they found a place where they've enjoyed the collegiality, collaboration, and can-do attitude characteristic of their colleagues.
Before finding his way to the University of Utah, Dr. Rothenfluh completed a Master's of Science in molecular biology at Universität Basel in the early '90s. He went on to complete a PhD in genetics at Rockefeller University, which he followed up with a postdoctoral fellowship at UC San Francisco. Dr. Rothenfluh subsequently spent nearly a decade as an assistant professor at UT Southwestern in Dallas, Texas before ultimately coming to the University of Utah in 2016. Throughout his career, flies—drosophila—have taken a leading role in Dr. Rothenfluh's research and findings.
As an outsider to Dr. Rothenfluh's vein of research, a natural question arises with the use of flies, particularly when it comes to understanding the human brain: why flies?
When discussing drosophila, Dr. Rothenfluh brings up world-renowned physicist, molecular biologist and behavioral geneticist, Seymour Benzer. He points to the observations Benzer made in noting that flies stand as a convenient intermediate step between the complexity of humans and the simplicity of yeast. That says nothing of the tremendous cost efficiency and scalability found in using drosophila.
Dr. Rothenfluh continues to cite Seymour Benzer's work as told in "Time, Love, Memory" by Jonathan Weiner. He notes that flies exhibit perhaps unlikely, albeit real similarities with humans in circadian rhythms—which Dr. Rothenfluh studied while working on his PhD—courtship, and learning and memory. Thus, flies become even more compelling test subjects for their translational relevance.
After noting that Seymour Benzer had many skeptics regarding the usefulness of studying flies and their brains, Dr. Rothenfluh notes how Benzer continues to be vindicated in his assertion that fly brains have translational worth. When talking about studying drosophila, Dr. Rothenfluh speaks in the modest tones of a scientist who defers to the data and says of flies that, "even though the brain looks very different, the logic and circuit organization of the brain may turn out to be more similar than we thought. I think both the combination of understanding the molecules as well as the logic of the circuits, might lead to more insights which might be somewhat translatable."
Image of a fly brain. The circle in the middle of Figure A is the ellipsoid body, a pre-motor center thought to be involved in alcohol tolerance.
Continuing to discuss translational application, Dr. Rothenfluh notes a recent publication he co-authored wherein the study led to the discovery of several new genes. But understanding the mechanisms of those genes is difficult. Thus, he says, "I think mechanistic validation, as well as mechanistic understanding of those molecules and genes is something that model organisms are really useful for."
Coming back to the fly as a drinking companion, Dr. Rothenfluh's research has shown tremendous promise in exploring addiction behavior through the study of flies. In his lab, they have found that much like humans, flies are initially averse to alcohol. He says with a smile, "people generally start out with low-percentage or sweet-tasting alcohol. And mice don't like it that much either. With mice, you have to literally sugar-coat it." He goes on to suggest one might naturally assume flies eat rotten things, so they must like alcohol. "It turns out, they don't. But this is brilliant because it is the same for us. It turns out that flies over time learn to like it."
Dr. Rothenfluh notes the perfection of this similarity. It is exactly what addiction is: "an experienced dependent liking." And with that addiction, there are two components. On the one hand, how sensitive are you
to the rewarding effects? And on the other, how sensitive are you to the aversive effects? Those who are more sensitive to the negative effects are less likely to become alcoholics. Embedded in this question is an unexplored frontier, which Dr. Rothenfluh has been studying. There is great promise in this area because of the potential to discover a way to make substances less appealing.
With a promising research frontier, Dr. Rothenfluh's work with flies will continue to be a compelling area of interest. So next time you swat a fly away from your drink, maybe consider sharing a sip and raising one to the tremendous work that Dr. Rothenfluh is doing.
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