NeURoscience | Volume 5 | 2020

NEUROSCIENCE University of Rochester | Ernest J. Del Monte Institute for Neuroscience Vol. 5 - 2020

University of Rochester | Winter 2019

The Next Generation On the frontlines of understanding Intellectual and Developmental Disabilities Winter 2019 PG 3

F R O M T H E D I R EC TO R ’ S D E S K

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John J. Foxe, Ph.D. Kilian J. and Caroline F. Schmitt Chair in Neuroscience Director, The Ernest J. Del Monte Institute for Neuroscience Professor & Chair, Department of Neuroscience

On the cover: Front: Emily Knight, M.D., Ph.D. Leona Oakes, Ph.D. Back: Laura Silverman, Ph.D. Tufikameni Brima, Ph.D. Photo by John Schlia

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s the weather breaks in Rochester, we enter a new season. Spring reminds us of new beginnings, bringing with it a sense of anticipation of what is to come – the research that’s underway and the discoveries that are yet to be made.

While the global COVID-19 pandemic has disrupted lives and threatened health, it is also a reminder of the importance of the work that we do every day and how science and collaboration can be harnessed to confront society’s greatest challenges.

I’m always proud to share how researchers and clinicians work in tandem. It is work that is unique to an academic medical center. Collaboration between those in the lab and those treating patients fosters unique opportunities to both advance research and improve care at the University.

Patients can, and often do, volunteer to be a part of research that could ultimately impact others diagnosed with the same disorder. At the same time, clinicians benefit from the insight of scientists who are improving our understanding of how these diseases develop and progress.

Our cover story focuses on four brilliant female researchers tackling some of the most complex disorders in neuroscience. As one of the flagship programs of the Del Monte Institute, Intellectual and Developmental Disabilities (IDD) is a field where crossdiscipline collaboration is imperative.

Researchers often work closely with clinicians and vice versa. Without the generosity, selflessness, and participation of research participants, much of the work done in our labs could not proceed.

As you will read, each woman featured

offers a unique perspective while sharing a common goal: to find ways to improve care and quality of life for families and patients living with an IDD. It’s always a pleasure to introduce you to new faculty in the institute. In this issue you’ll meet Adam Snyder, Ph.D., who came to the University of Rochester in July 2018 as an assistant professor in Brain and Cognitive Sciences, Neuroscience, and the Center for Visual Science. His research focuses primarily on vision, visual attention, and memory.

He and his wife have found a kinship with the area, between the culture of the city of Rochester and the countryside of the Finger Lakes.

In an effort to highlight the next generation of researchers we are shining a spotlight on Ian DeAndrea-Lazarus, who is a M.D./Ph.D. candidate in the Medical Scientist Training Program.

DeAndrea-Lazarus was funded recently with a prestigious fellowship award to support his research that is comparing the impact that access to language and the effect language has on the visuospatial attention of people who are deaf. As a scholar who is deaf DeAndreaLazarus also hopes to inspire all parents to teach their children American Sign Language. In this issue you will learn more about his effort that has already reached hundreds of thousands of people.

In Science,

John J. Foxe, Ph.D.

NEWS BRIEFS

Brain ‘Drowns’ in Its Own Fluid after a Stroke Cerebral edema, swelling that occurs in the brain, is a severe and potentially fatal complication of stroke. New research, which was conducted in mice and appears in the journal Science, shows for the first time that the glymphatic system – normally associated with the beneficial task of waste removal – goes awry during a stroke and floods the brain, triggering edema and drowning brain cells.

“These findings show that the glymphatic system plays a central role in driving the acute tissue swelling in the brain after a stroke,” said Maiken Nedergaard, M.D., D.M.Sc., co-director Center for Translational Neuromedicine and senior author of the article.

“Understanding this dynamic – which is propelled by storms of electrical activity in the brain – point the way to potential new strategies that could improve stroke outcomes.”

The study, which was co-authored by Humberto Mestre, M.D., a neuroscience Ph.D. student in the Nedergaard lab, showed that after a stroke, a spreading wave of depolarizing nerve cells releases vast amounts of potassium and neurotransmitters into the brain. This causes blood vessels to contract, creating a vacuum that floods brain tissue with cerebral spinal fluid, drowning nerve cells, and causing the brain to swell.

The findings suggest potential new treatment strategies that used in combination with existing therapies focused on restoring blood flow to the brain quickly after a stroke. The study could also have implications for brain swelling observed in other conditions such as subarachnoid hemorrhage and traumatic brain injury.

In February, Nedergaard was recognized by the American Heart Association/American Stroke Association with the Thomas Willis Lecture Award for scientific contributions to stroke research.

Small eye movements are critical for 20/20 vision Small eye movements play a large role in visual acuity, according to research published in Nature Communications by Professor of Brain and Cognitive Sciences Michele Rucci and Janis Intoy, a neuroscience graduate student at Boston University and a research assistant in Rucci’s lab in Rochester.

It was previously assumed that visual acuity – the ability to discern objects from a distance – was primarily determined by the optics of the eye and anatomy of the retina.

University of Rochester photo / J. Adam Fenster Using the Snellen eye chart researchers stabilized the chart on observers’ retinas by continually updating the display according to eye movements, counteracting the movements’ effects. This led to a drastic reduction in visual acuity. The observers, who normally had 20/20 vision, were on average now only able to read to approximately line six of the chart, indicating 20/30 vision.

Because of the large role fixational eye movements play in visual acuity, this research suggests doctors should carefully consider and examine these movements in people with impaired visual acuity, such as myopia (nearsightedness) and hyperopia (farsightedness). It is still unclear whether abnormal eye movements cause impaired visual acuity, but this research shows it is possible and therapies involving eye movements may be helpful.

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NEWS BRIEFS

UR Hosts 2020 Rochester Brain Bee The 4th annual Rochester Brain Bee was held February 1st at Goergen Hall at the University of Rochester. Neuroscience and Brain and Cognitive Sciences students hosted the event that tests the neuroscience knowledge of high school students. Webster Thomas High School senior Scott Schleede took the top prize.

Children with ASD now part of ABCD Study Children with Autism Spectrum Disorder (ASD) will now be a part of the Adolescent Brain Cognitive Development (ABCD) study at URMC. Frederick Schindler, B.S. ’57, Ph.D. generously contributed nearly half a million dollars to the study to include children with ASD to the data already being collected on adolescents. URMC is one of 21 sites across the country participating in the ABCD study, the largest study of adolescent brain development ever in the United States.

Schindler's contribution will also fund the use of high-density EEG measures, which test electrical activity in real time, providing a more detailed picture of brain activity than the MRI exams currently used in the study.

Edward Freedman, Ph.D. gives Frederick Schindler, Ph.D. a tour of the Center for Advanced Brain Imaging and Neurophysiology. Schindler received his B.S. in chemistry from UR in 1957.

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The Next Generation An up-and-coming group of researchers are on the frontlines of understanding Intellectual and Developmental Disabilities

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IDD

he complex and vast family of neurological disorders that comprise Intellectual and Developmental Disabilities (IDD) is being met head on by researchers at the Del Monte Institute for Neuroscience. These efforts are bolstered by a large contingent of clinician researchers who serve patients and families with these disorders and are critical partners in efforts to advance care through research.

URMC is home to many recognized female leaders and innovators in the field of IDD and is one of the flagship research programs of the Del Monte Neuroscience Institute. This foundation is being strengthened by a new generation of female researchers who are studying IDD with an eye toward developing new tools that will lead to early diagnosis, more effective behavioral interventions, and ultimately, new treatments that slow the progress of IDD.

Laura Silverman, Ph.D. (left). Leona Oakes, Ph.D., Tufikameni Brima, Ph.D., Emily Knight, M.D., Ph.D.

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Oakes (left) and Knight

Collaboration gives the work of Emily Knight, M.D., Ph.D., second year developmentalbehavioral pediatrics fellow in the Department of Pediatrics, an edge. Knight’s research focuses on autism spectrum disorder (ASD), including developing new and inclusive ways to collect data from children with the disorder. Many research techniques used to test children require a spoken response or the ability to follow complex directions, limiting their use for patients who are nonverbal. Knight’s work includes children of all levels of language and ability in order to better understand this patient population with the hope this may eventually help improve diagnosis and treatment. “There are so many people with varied expertise who are looking at ASD from different perspectives. I think when you have that critical mass you can do some really interesting work.” Knight is collecting data by measuring brainwaves as children listen to specific patterns of sounds while participating in an activity they enjoy.

She is investigating whether this brain activity will be able to offer insight into how children with autism process sounds, and how that relates to their interactions with other people and their environment.

Leona Oakes, Ph.D., a senior instructor in the Departments of Neuroscience and Pediatrics, is combing through the data of a 15-year follow-up study on the long-term outcomes of early intervention in individuals with autism spectrum disorder (ASD). She is one of several researchers studying whether the benefits of early intervention are sustained as the people with ASD age. “We know that early intervention has immediate effects. But having evidence that it has lasting long-term effects, including scholastic achievement and protections against mental health issues and adaptive skills, would show these interventions are helping people contribute to society at a higher potential,” Oakes said. “We have a role as a society, to try to create a more accommodating world for people that are different, where they are not just accepted but also in an environment where they can flourish, add their unique perspectives, and their unique understanding of the world.”

Laura Silverman, Ph.D., an associate professor in Developmental & Behavioral Pediatrics in the Department of Pediatrics, is studying how individuals with autism process language and hand gestures during typical social interactions. Her focus is communication and multisensory functioning in ASD. Silverman employs eye-tracking and computational linguistic methodologies, in collaboration with colleagues in music and neuroscience. “Doing research makes me more aware of cutting-edge therapies and also shows me how people with autism

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process information,” Silverman said. This understanding enables her to better communicate with parents in her clinical work, explain why their child may be acting a certain way, and give them tools that may help. She’s also in a unique position to work beyond clinical work and research. As a co-director of the Leadership Education and Neurodevelopmental Disabilities (LEND) Program, Silverman helps teach professionals from different disciplines how to be leaders in the field of developmental disabilities.

While a large contingent of researchers and clinicians are studying autism, many other rare neurodevelopmental disabilities are also the focus of research at the Medical Center.

The University of Rochester Batten Center is a comprehensive clinical and research center that supports families while investigating treatments that could slow progression of the disease. Batten disease is a fatal genetic disorder of the nervous system that typically begins in childhood. Tufikameni Brima, Ph.D. is a research assistant professor in the Department of Neuroscience and has focused much of her career on understanding rare neurodevelopmental disorders, like Batten disease and Rett syndrome – another rare genetic disorder. Working in the URMC Cognitive Neurophysiology Lab, Brima is focused on developing objective quantitative measures of brain function in patients who cannot be evaluated with standard cognitive tests due to the nature of their disease. “It is imperative to find an effective way to assess their condition,” Brima said. “This will help when it comes to diagnosis, development of drugs, and advocacy of therapies.” For example, patients with Rett are non-verbal and those with Batten can lose sight. Using an electroencephalogram (EEG), Brima is able to investigate cognitive processing and language comprehension in non-verbal individuals with these rare disorders. She hopes that in addition to objective measures of brain function, her findings will also contribute to the development of better communication devices for these individuals while enabling scientists and clinicians to accurately track the disease’s progress and the effect of current and future therapies. Furthermore, system biomarkers of these disorders could help research and clinical work in other neurodevelopmental disabilities.

The work of these researchers, as well as efforts of many others at the University of Rochester who are studying IDD, is advancing our understanding of the brain’s complex networks and how we process external stimuli. The close collaboration with clinicians who provide care will enable this research to transform how we provide care and improve the quality of life for patients and families diagnosed with neurodevelopmental disorders.

Brima (left) and Silverman

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F A C U LT Y P R O F I L E

Q&A with Adam Snyder, Ph.D. Adam Snyder, Ph.D., joined the Del Monte Institute for Neuroscience in July 2018 as an assistant professor in Brain and Cognitive Sciences, Neuroscience, and the Center for Visual Science. He received his B.A. in Language and Mind from New York University and went on to complete his Ph.D. in Cognitive Neuroscience from the City College of New York. His research focuses primarily on vision, visual attention and memory.

Tell us a little bit about your research.

The fundamental problem faced by the brain that we’re trying to solve is that there is a lot more information in the environment than the human brain can process effectively.

We are using animal and computer models to study vision, visual attention, and memory. It is a major challenge, but we are working to figure out how the brain uses goals to determine which information to process from moment to moment.

What brought you to the University of Rochester?

The Center for Visual Sciences at the University of Rochester is world-renowned. That coupled with the large community of people here doing similar research and studying vision and visual attention makes for an ideal environment to study and grow in my area of research. It is great to be in an environment where you are rubbing shoulders with the leaders in your field. Another contributing factor, was the institution’s big commitment to neuroscience and growing the neuroscience, particularly within the Del Monte Institute.

Is there anyone that you were looking forward to collaborating with before you came here or are looking forward to collaborating with, as you’re here?

I have a few collaborations that are ongoing, and others that are pending. I’m closely collaborating with Tatiana Pasternak, Ph.D. Her research is very similar to mine, thinking about how the brain makes decisions about which information to process. She has a great reputation in the field as a leader in that regard. Having the opportunity to work with her and learn from her experiences really has been excellent.

Edmund Lalor, Ph.D., is a faculty member I look forward to working with. He is an associate professor in Biomedical Engineering and Neuroscience, and studies human attention.

With him I’m interested in collaborating to translate work in animal models to human brain function. Here in Brain and Cognitive Sciences, I’m working on a new collaboration with Ralf Haefner, Ph.D., whose excellent computational and theoretical neuroscience help develop theories that guide our experimental work.

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How did you become interested in your field of study?

I went into college interested in linguistics. I was interested in cognitive science and I thought that language was interesting because it was a uniquely human behavior. In the course of studying linguistics, I became interested in neural mechanisms of cognition. This moved me away from language, in that sense, and into the visual system. When I started to learn more about how the brain processes visual information it became apparent that figuring out which information to process and how the brain decides that is a very early step to understanding this.

What do you do outside the lab?

I enjoy the pace of the city of Rochester, and being able to go

down to the Finger Lakes for sightseeing, as well as touring wineries and breweries. My wife is a visual artist, so we also spend a lot of time going to arts events in the area.

Is there one question that you want to see answered before you finish your career?

It is a very exciting time to be involved in neuroscience research. We’ve made huge strides in the last five years in both the amount and complexity of the data that we can collect, and the computational tools to analyze those data. With that said, we are really at a stage where we don’t know what the right questions are. I would like to know the answer to – what are the fundamental properties of how the brain works that we need to investigate?

S T U D E N T S P OT L I G H T

Ian DeAndrea-Lazarus Ian DeAndrea-Lazarus, M.D. and Ph.D. candidate in the Medical Scientist Training Program, was awarded the distinguished Ruth L. Kirschstein National Research Service Award Individual Predoctoral Fellowship to Promote Diversity in Health Related Research (F31) from the National Center for Deafness and Communication Disorders.

This fellowship will support DeAndrea-Lazarus’ research using electroencephalography (EEG) that compares the effect that deafness and early access to sign language has on visuospatial attention in people who are deaf. Specifically, how the brains of deaf native signers, or people born to deaf parents and who acquired American Sign Language as their first language, suppress irrelevant stimuli in their peripheral visual field – or distinguish between significant and insignificant information – when compared to hearing people who did not learn to sign.

DeAndrea-Lazarus believes this could identify the effects of deafness and language deprivation – limited exposure to early language – in children who are deaf that can cause cognitive, academic, behavioral, and socio-emotional deficits. Previous studies have reported attentional deficits in deaf people, but they did not consider the effect of delayed sign language acquisition in this population.

“We’re becoming more aware of the effects of language

deprivation, particularly in the context of technological advancements like cochlear implants. The technology has improved significantly over the years, but that can lead to a lot of misconceptions such as the idea that access to sound via cochlear implants alone is sufficient to fully acquire language,” DeAndrea-Lazarus, who has an implant himself, said. “It has been shown that there is so much variation in language outcomes, even in those who were implanted as early as the age of one.”

As a scholar who is deaf, DeAndrea-Lazarus has been using social media as a tool to show how young children can learn to sign. Video clips of him and his young son signing have gone viral with hundreds of thousands of views. He hopes it inspires others to teach children sign language. “We can communicate at an earlier age than at which our vocal cords develop, so this can have an impact on hearing kids as well.”

This still image from a video shows Miles fingerspelling the word he is reading on the cover of the book DADA by Jimmy Fallon to his dad, Ian, and mom, Connor.

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NEWS BRIEFS

New Book Details Roadmap to Prevent and Treat Parkinson’s

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new book titled “Ending Parkinson’s Disease: A Prescription for Action” authored by URMC neurologist Ray Dorsey, M.D., lays out a new vision to prevent, advocate for, care for, and treat this major and growing global health threat.

“Parkinson’s disease is a looming pandemic and we are woefully unprepared to meet this challenge – many people remain undiagnosed and untreated, research funding for the disease has stagnated, and the most effective treatment is now a half century old,” said Dorsey, the director of the Center for Health + Technology. “At least some cases of Parkinson’s are manmade and, therefore, preventable.”

Parkinson’s disease is the fastest growing neurological disorder in the world, outpacing Alzheimer’s. Over the past 25 years, the number of people with the condition has jumped from three million to more than six million, and by 2040, it is projected to double again.

Parkinson’s and its rise have been fueled by environmental exposures to harmful chemicals. The two biggest culprits currently still widely in use are the herbicide paraquat and the industrial solvent trichloroethylene. Not only are agricultural and industrial workers at risk of exposure, but these chemicals also enter the food chain, water supply, reside in the soil in brownfield sites, and impact indoor air quality.

Confronting the Parkinson’s pandemic will require harnessing technology, lowering barriers to access, and marshalling the same focus and resources employed with success to address other public health challenges, such as polio, HIV, and breast cancer.

Additional co-authors of the book include Todd Sherer, Ph.D., CEO of the Michael J. Fox Foundation, Mike Okun, M.D., with the University of Florida, and Bastiaan R. Bloem, M.D., Ph.D., with Radboud University in the Netherlands. Proceeds from sales of the book will support Parkinson’s research at URMC and other institutions.

"This book offers a clear pathway forward - while sounding out a resounding clarion alarm; prompting action - that we should all pay heed to!"

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- Davis Phinney, Founder, Davis Phinney Foundation for Parkinson's

Haber Honored for Research in Neurological and Psychiatric Disorders For decades, Suzanne Haber, Ph.D., has helmed research projects that have produced life–changing findings for individuals and families suffering from neurological and mental health disorders. The Society of Biological Psychiatry for Research on Mental Disorder is honoring her for that work, bestowing her with the prestigious 2020 Gold Medal Award. Her work demonstrates the specific hard-wired connections between regions of the brain that are associated with normal decision making, emotional and cognitive control, and the connectional abnormalities in those circuits that are linked to a wide range of mental health disorders, including obsessivecompulsive disorder, drug abuse and addiction, schizophrenia, and motor control disorders such as Parkinson’s disease. Haber is Dean’s Professor in the Department of Pharmacology and Physiology, and is a professor of Neuroscience, Brain and Cognitive Science, and Psychiatry at the University of Rochester.

Del Monte Institute for Neuroscience Executive Committee John Foxe, Ph.D.

B. Paige Lawrence, Ph.D.

Director, The Ernest J. Del Monte Institute for Neuroscience Kilian J. and Caroline F. Schmitt Chair in Neuroscience Professor and Chair, Department of Neuroscience

Wright Family Research Professorship - Dean’s Office M&D Professor and Chair, Department of Environmental Medicine

Bradford Berk, M.D., Ph.D.

John Romano Professorship in Psychiatry Professor and Chair, Department of Psychiatry

Director, The University of Rochester Neurorestoration Institute Professor of Medicine, Cardiology

Robert Dirksen, Ph.D.

Hochang (Ben) Lee, M.D.

Shawn Newlands, M.D., Ph.D., M.B.A. Professor and Chair, Department of Otolaryngology

Lewis Pratt Ross Professorship of Pharmacology and Physiology Professor and Chair, Department of Pharmacology and Physiology

Webster Pilcher, M.D., Ph.D.

Diane Dalecki, Ph.D.

Ernest & Thelma Del Monte Distinguished Professor in Neuromedicine Professor and Chair, Department of Neurosurgery

Distinguished Professor of Biomedical Engineering Chair, Department of Biomedical Engineering

Jennifer Harvey, M.D.

Duje Tadin, Ph.D. Professor, Department of Brain & Cognitive Sciences

Professor and Chair, Department of Imaging Sciences

Robert Holloway, M.D., M.P.H. Edward A. and Alma Vollertsen Rykenboer Chair in Neurophysiology Professor and Chair, Department of Neurology

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Subscribe to NeURoscience Perspectives on YouTube today This interview series features John Foxe, Ph.D., director of the Del Monte Institute for Neuroscience, and some of the brilliant minds studying neuroscience as they visit the University of Rochester.

Subscribe to the Del Monte Institute for Neuroscience YouTube channel at delmonte.urmc.edu/youtube for insight into their journey and research in the field of neuroscience.

Helen Tager-Flusberg, Ph.D. with John Foxe, Ph. D. Inset: Jeffrey Macklis, M.D.

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