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.
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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