NeURoscience | Vol 14 | 2022

NEUROSCIENCE University of Rochester | Ernest J. Del Monte Institute for Neuroscience Vol. 14 - 2022

Many minds, many methods, one brain PG 4

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, Ernest J. Del Monte Institute for Neuroscience

Professor & Chair, Department of Neuroscience

On the cover From Left: Ed Freedman, Ph.D., associate professor of Neuroscience and Principal Investigator (PI) of the Frederick J. and Marion A. Schindler Cognitive Neurophysiology Laboratory stands with co-PI John Foxe, Ph.D., Neuroscience Department chair and director of the Del Monte Institute for Neuroscience.

Photo: John Schlia Photography

e are coming off another incredible academic year – our students thrived and our faculty shone. A number of our faculty were recognized for their excellence in mentoring students and postdocs, including Dr. Ania Majewska who received the highly prestigious 2022 Landis Outstanding Mentorship Award from the National Institute of Neurological Disorders and Stroke (NINDS). Ania represents the very best in our ongoing collective efforts to create lab spaces that exemplify inclusive caring mentorship and our commitment to prepare the next generation of exceptional scientists and leaders.

Our youngest trainees wrapped up a successful second year of the NEUROEAST program – the students from East High in Rochester gave final presentations in early June. As that program concluded, 10 undergraduate students from City College of New York entered neuroscience labs across the University for the second summer of NEUROCITY. We are immensely proud of the impact these programs are having on the inclusivity and diversity of lab access.

The cover story goes inside the lab where I am a co-principal investigator alongside Dr. Ed Freedman. It was recently renamed the Frederick J. and Marion A. Schindler Cognitive Neurophysiology Laboratory in recognition of a remarkable couple who are dedicated to children with developmental disabilities, particularly those with autism spectrum disorder. Their philanthropy allows our lab to ask difficult questions that will in time lead to a better understanding of the brain mechanisms in autism and other disorders that will improve treatment

Del Monte Institute for Neuroscience Executive Committee John Foxe, Ph.D., Chair, Department of Neuroscience Bradford Berk M.D., Ph.D., Professor of Medicine, Cardiology Robert Dirksen, Ph.D., Chair, Department of Pharmacology & Physiology Diane Dalecki, Ph.D., Chair, Department of Biomedical Engineering Jennifer Harvey, M.D., Chair, Department of Imaging Sciences Robert Holloway, M.D., M.P.H., Chair, Department of Neurology

and care of those with intellectual and developmental disabilities (IDD). Mapping the neuropathological processes that give rise to an IDD is a cornerstone of our lab, which is home to dozens of researchers and a large portfolio of ongoing studies.

I’m excited for you to meet a musician turned neuroscientist. Dr. Aaron Nidiffer is a postdoctoral fellow in the lab of Dr. Edmund Lalor, and he shares his unique perspective on his interest in sound and the brain.

We are all still buzzing from the fantastic energy that was created during our recent symposium in neurodevelopment. We are profoundly grateful to all the brilliant scientists who graciously traveled to Rochester for our first in-person symposium in two years. It is fair to say the joint effort of the Del Monte Institute for Neuroscience and the Intellectual and Developmental Disabilities Research Center was a resounding success. I want to extend my gratitude to all who traveled to join us, particularly our speakers, and the organizing committee who were most capably led by our own Dr. Kuan Hong Wang.

As you read through the pages that follow, I hope you will get a good feel for another incredible few months of advancements and achievements. As always, I am proud to be a part of this incredible group of scientists.

In Science,

John J. Foxe, Ph.D.

Paige Lawrence, Ph.D., Chair, Department of Environmental Medicine Hochang (Ben) Lee, M.D., Chair, Department of Psychiatry Shawn Newlands, M.D., Ph.D., M.B.A., Chair, Department of Otolaryngology Webster Pilcher, M.D., Ph.D., Chair, Department of Neurosurgery University of California, Berkeley Steven Silverstein, Ph.D., Professor, Department of Psychiatry Duje Tadin, Ph.D., Chair, Department of Brain & Cognitive Sciences

UNIVERSITY OF ROCHESTER | ERNEST J. DEL MONTE INSTITUTE FOR NEUROSCIENCE

NEUROSCIENCE Editor/Writer Kelsie Smith Hayduk Kelsie_Smith-Hayduk@ urmc.rochester.edu Contributors Karen Black Mark Michaud Feature Photography John Schlia Photography Designer Beth Carr

NEWS BRIEFS

The Art of Smell:

Research suggests the brain processes smell both like a painting and a symphony

New research published in Cell Reports suggests that our brain processes smell in multiple ways – like a painting – a snapshot of the flickering activity of cells – captured in a moment in time, and like a symphony, an evolving ensemble of different cells working together to capture the scent.

Krishnan Padmanabhan, Ph.D., an associate professor of Neuroscience lead the study that developed a model to simulate the workings of the early olfactory system – the network the brain relies on for smelling. Employing computer simulations, he and graduate student Zhen Chen found a specific set of connections, called centrifugal fibers, which carry impulses from other parts of the central nervous system to the early sensory regions of the brain, played a critical role. These centrifugal fibers act as a switch, toggling

between different strategies to efficiently represent smells.

When the centrifugal fibers were in one state, the cells in the piriform cortex – where the perception of an odor forms – relied on the pattern of activity within a given instant in time. When the centrifugal fibers were in the other state, the cells in the piriform cortex improved both the accuracy and the speed with which cells detected and classified the smell by relying on the patterns of brain activity across time.

“These findings reveal a core principle of the nervous system, flexibility in the kinds of calculations the brain makes to represent aspects of the sensory world,” said Padmanabhan. “Our work provides scientists with new tools to quantify and interpret the patterns of activity of the brain.”

Daily steroids safe and slow progression of Duchenne muscular dystrophy New research published in JAMA recommends daily steroid doses for children with Duchenne muscular dystrophy (DMD), marking a significant change in how the disease is treated.

University of Rochester Medical Center neurologist Robert Griggs, M.D., and Michela Guglieri, M.D., with Newcastle University in the U.K., led the study, which was conducted by a global team of researchers dedicated to improving care for this fatal disease. DMD is a condition found almost exclusively in boys and characterized by muscle weakness, which appears at age 3-4 and progresses rapidly, leading to significant disability and often fatal by late teens.

Participants were assigned to three groups consisting of daily regimens of prednisone or deflazacort, or intermittent prednisone, and followed for three years. The researchers

found that the daily regimens of both drugs significantly slowed disease progression as measured by strength testing and muscle function, as compared to the intermittent group. While the daily regimen increased side effects overall, there were minimal serious side effects.

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NEWS BRIEFS

New research finds the risk of psychotic-like experiences can start in childhood It has long been understood that environmental and socioeconomic factors – including income disparity, family poverty, and air pollution – increase a person’s risk of developing psychotic-like experiences, such as subtle hallucinations and delusions that can become precursors to a schizophrenia diagnosis later in life. Research has long focused on young adults but now, thanks to the data from the Adolescent Brain Cognitive Development (ABCD) Study, researchers at the University of Rochester have found these risk factors can be observed in preadolescent children.

The research published in Frontiers in Psychiatry and lead by David Dodell-Feder, Ph.D., assistant professor of Psychology and Neuroscience, found that the more urban of an environment a child lived in – proximity to roads, houses with lead paint risks, families in poverty, and income disparity – the greater number of psychotic like experiences they had

over a year’s time. These findings are in line with past research conducted in young adults, but have not been found like this in preadolescence.

“It is disconcerting that the association between these exposures and psychotic-like experiences are already present in late childhood,” said Dodell-Feder. “The fact that the impact of these exposures may occur as early as pre-adolescence highlights the importance of early prevention.”

The University of Rochester Medical Center is one of 21 research sites across the country collecting data for the National Institutes of Health ABCD Study. Since 2017, 340 children from the greater Rochester area have been participating in the 10-year study. In all, the study is following 11,750 children through early adulthood looking at how biological development, behaviors, and experiences impact brain maturation and other aspects of their lives, including academic achievement, social development, and overall health.

How the brain interprets motion while in motion New findings about how the brain interprets sensory information may have applications for treating brain disorders and designing artificial intelligence. Greg DeAngelis, Ph.D., the George Eastman Professor of Brain and Cognitive Sciences at the University of Rochester, led the research published in eLife that describes a novel neural mechanism involved in causal inference – a key to learning, reasoning, and decision making – that helps the brain detect object motion during self-motion.

This neural mechanism has a particular combination of response properties, which makes it well-suited to contribute to the task of distinguishing between self-motion and the motion of other objects.

“Although the brain probably uses multiple tricks to solve this problem, this new mechanism has the advantage that it can be performed in parallel at each local region of the visual field, and thus may be faster to implement than more global processes,” DeAngelis said.

“This mechanism might also be applicable to autonomous vehicles, which also need to rapidly detect moving objects.”

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UNIVERSITY OF ROCHESTER | ERNEST J. DEL MONTE INSTITUTE FOR NEUROSCIENCE

P O S T D O C TO R A L S P OT L I G H T

Aaron Nidiffer, Ph.D.

Aaron Nidiffer, Ph.D.

Aaron Nidiffer, Ph.D., a postdoctoral associate in the lab of Edmund Lalor, Ph.D., received his doctoral degree in Hearing and Speech Sciences from Vanderbilt University. His research focuses on how the brain interprets visual speech and simultaneously processes two different types of information conveyed by the lips – timing and shape.

“I feel like the visual system is kind of an underdog in the speech domain. It does not get enough credit for doing some of the brain’s heavy lifting,” said Nidiffer. “In our research we mostly present audiovisual speech to participants. We work with participants who are Deaf, with and without a cochlear implant, as well as hearing participants. We are looking to see how the brain utilizes these visual inputs to help the auditory system make its linguistic representation of speech, and specifically how people with different levels of experience with acoustic speech use those visual inputs.”

His work also aims to understand how the visual system might be making its own linguistic representations. Indicating how some people who are Deaf use lip reading to understand what others are saying. “I believe this is happening through

Visemes, the brain response to linguistic features of visual speech, are apparent in visual cortex (blue arrows) during visual only speech.

During audiovisual speech, responses to the acoustic envelope can be found in visual and auditory cortex (red arrow).

some linguistic processes in the visual system related specifically to the shape of the lips rather than their timing.”

Nidiffer has long been interested in how we make sense of our surroundings, and first remembers becoming particularly curious about the brain while playing music. “I was in my high school’s band and also played guitar in a couple of rock bands throughout college. One of the things that I always thought about was how cool it is that a group of musicians can play their own parts, creating unique vibrations that come together to be perceived as one coherent unit but can still be separated by focusing on a particular instrument.”

Outside of the lab, Nidiffer reads as much primary

Nidiffer played the saxophone in his high school marching band. He also sang while playing the banjo at an open mic during college.

research as possible. He follows advice once given to him. “It is impossible to do science in a vacuum of your knowledge.

You have to know about and use other people’s tools to understand how to design a well-controlled experiment and then how to interpret it.” He also volunteers for journal clubs to practice explaining what he has learned from reading to others. These strategies have also helped him become a better writer. For those thinking about pursuing a Ph.D., Nidiffer has some advice. “Join a lab,” he said. “Doing this as an undergraduate is a great way to understand how science is done, how experiments are designed, how to gain practical use in addition to the theoretical students gain from reading.

I believe the earlier someone understands how to do science the better.”

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F E AT U R E

The Frederick J. and Marion A. Schindler Cognitive Neurophysiology Laboratory

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he hum of a treadmill in the distance greets you stepping off the elevator into the Frederick J. and Marion A. Schindler Cognitive Neurophysiology Laboratory (CNL) at the University of Rochester. The noise is the Mobile Brain/Body Imaging system (MoBI), and its whirr is matched by the sound of the nearly 50 scientists who are in and out of the lab at any given time, aiming to answer difficult questions relating to the brain.

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“Our lab paints on a broad canvas using many different tools, investigating different conditions. It’s a more unconventional approach to neuroscience that doesn’t constrain us to one problem as scientists,” said John Foxe, Ph.D., one of the principal investigators of the CNL and director of the Del Monte Institute for Neuroscience.

“Understanding what goes awry in the brain, in any disorder or disease, is imperative to our overall understanding of the brain.”

UNIVERSITY OF ROCHESTER | ERNEST J. DEL MONTE INSTITUTE FOR NEUROSCIENCE

To date, the lab’s major contributions have been in multisensory integration – how the senses are knit together in the brain and how this function goes awry in neurodevelopmental disorders like autism spectrum disorder.

The lab has also expanded our understanding of the role of oscillations – or brain rhythms in attention. This research has expanded into clinical populations – including people with autism and people who are Deaf – and has found clear differences in how activity in spatial attention is deployed in those populations.

Emma Mantel, technical associate in the CNL demonstrates how the Mobile Brain/Body Imaging system (MoBI) works.

The lab’s co-PI Ed Freedman, Ph.D., describes the ceiling of the lab as a huge umbrella with common themes threading all the research together. “Our main interest is trying to understand how the brain integrates sensory information and generates behaviors and how does it fail in things like aging and degenerative diseases like Alzheimer's, Parkinson's disease, or how is it different in people with autism or people with other intellectual and developmental disabilities (IDD).”

Looking into the brain By harnessing the electrical nature of the brain, researchers can open a window to investigate its function and connections in humans. Functional magnetic resonance imaging (fMRI) shows activity in the brain spanning across a network of different regions – anterior and posterior temporal lobes, inferior parietal cortex, and inferior frontal cortex. This insight into the blood flow in the brain during a specific task enables researchers in the CNL a better understanding of mechanisms that may play a role in neurodevelopmental disorders.

“Because fMRI is a non-invasive imaging technique it allows us to use it safely, effectively, and repeatedly to also evaluate changes in brain function over time during development or to assess therapeutic effectiveness,” said Madalina Tivarus, Ph.D., associate professor of Imaging Sciences and Neuroscience and director 3D Post-Processing Laboratory.

“Significant advances have been made allowing the design of fMRI experiments to mirror behavioral paradigms, and provide excellent spatial functional localization of brain function. When combined with other techniques such as high-density EEG, it offers an even better understanding of brain function and dysfunction.”

Knowing when the brain responds is also a data point that assists in unraveling its complex nature. Electroencephalogram (EEG) is a cornerstone in the lab that can measure the electrical activity in the brain from the scalp surface and pinpoint when the brain is responding. Research Assistant Professor Tufikameni Brima, Ph.D., employs EEG to explore cognitive processing and language comprehension in nonverbal individuals with Rett Syndrome and Batten disease – two rare genetic disorders extensively studied in the lab.

It aids in the effort of finding a way to routinely use EEG as part of the screening protocols – particularly in non-verbal patients. In 2020, the National Institute of Child Health and Human Development (NICHD) named the University an Intellectual and Developmental Research Center to elevate this type of work. The University of Rochester Intellectual and Developmental Research Center (UR-IDDRC) joins the already established University Centers for Excellence in Developmental Disabilities Education, Research, and Service (UCEDD) – with a

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Leona Oakes, Ph.D., (right) assistant professor of Pediatrics and Neuroscience, discusses her research with Foxe (left). She is one of four faculty members in the CNL. Her research focuses on early intervention in individuals with autism spectrum disorder.

focus on training and service – and Leadership Education in Neurodevelopmental and Related Disabilities (LEND) – with a focus on education. The University is one of a handful of institutions with the trifecta of NIH awards related to IDD. Foxe is co-director of the UR-IDDRC, Freedman is co-director of the Translational Neuroimaging and Neurophysiology Core, and many of the CNL faculty members are also invested in IDD research.

"It is exciting and rewarding to see how my training as a cognitive neuroscientist bears on the IDD research efforts of our team,” said Lars Ross, Ph.D., research assistant professor in Imaging Sciences and Neuroscience. “I am dedicated to using my skills and expertise to help us understand the unique sensory experience and development of individuals with intellectual disabilities.”

Stepping into the future of science Recreating/replicating real-world experiences in a lab setting is an ongoing challenge. It is a challenge the MoBI

From left: Freedman, Ross, and Tivaras (right) prepare patient for fMRI. Ross and Tivaras are both faculty members in the CNL.

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attempts to overcome. The platform, exclusive to the CNL at the UR, combines virtual reality, brain monitoring, and motion capture technology. While participants walk on a treadmill or manipulate objects on a table, 16 high-speed cameras record the position markers with millimeter precision, while simultaneously measuring brain activity.

“The MoBI allows us to better understand how the brain functions in everyday life,” said Freedman. “It gives us insight into how a young healthy brain is able to switch tasks, which in turn helps us better understand what’s going awry in a brain with a neurodegenerative disease like Alzheimer’s disease.”

Freedman recently lead a study published in Cerebral Cortex that found some young and healthy people improve performance on cognitive tasks while walking by changing the use of neural resources. Using the MoBI researchers monitored brain activity, kinematics, and behavior of 26 healthy 18 to 30-year-olds as they looked at a series of images, either while sitting on a chair or walking on a treadmill. The EEG data

Tufikamani Brima, Ph.D., delivers a talk on her Rett Syndrome research from a podium in a Medical Center lecture hall (May 2022). Brima is a faculty member in the CNL.

UNIVERSITY OF ROCHESTER | ERNEST J. DEL MONTE INSTITUTE FOR NEUROSCIENCE

showed that the 14 participants who improved at the task while walking had a change in frontal brain function which was absent in the 12 participants who did not improve. This brain activity change exhibited by those who improved at the task suggests increased flexibility or efficiency in the brain. This research could guide scientists to identify a possible marker for ‘super agers’ or people who have a minimal decline in cognitive functions. This marker would be useful in helping better understand neurodegenerative diseases.

Dedication to long-term studies Since 2017, the CNL has been one of 21 locations collecting data for the largest long-term study of brain development and child health. Funded by the National Institutes of Health (NIH), the Adolescent Brain Cognitive Development (ABCD) study collects data from more than 11,000 nine and 10-yearolds over 10 years. More than 300 of the participants, now in their teens, are from Rochester.

“This is a phenomenal study to be a part of,” said Freedman, “The power of the study is that it's observational. We will see things happen to the kids in the cohort and be able to learn by looking backward to see where or when it may have been predicted. We can then go forward and have a better idea of when and how to intervene with other kids to help them avoid trouble. It is an incredible effort to understand adolescence and the brain.”

The study’s open science model gives researchers across the country access to this data, and as a result, dozens of studies have been published. The CNL has led several studies using this database – including findings related to the impact

The Mobile Neurophysiology Testing van allows for mobile COVID-19 testing for people enrolled in the National Institutes of Health (NIH) Rapid Acceleration of Diagnostics-Underserved Populations (RADx-UP) project being led Medical Center researchers. They have partnered with the Mary Cariola Center School in Rochester to study how COVID-19 spreads in the school, staff, and people with IDDs.

From right: Foxe and Freedman work with research participant in the Mobile Brain/Body Imaging system (MoBI) in the CNL.

of caffeine on a developing brain in utero and the relationship between cognition and breastfeeding.

The lab’s success in this large study and its role in the IDDRC led to a more recent partnership aiming to understand better how COVID-19 impacts students and staff in schools that serve students with IDDs. Funded by the NIH Rapid Acceleration of Diagnostics-Underserved Populations (RADxUP), researchers from the University of Rochester Medical Center (URMC) work with students and staff at the Mary Cariola Center School in Rochester, to study how COVID-19 spreads in the vulnerable population the agency serves.

The broad stroke of one lab On any given day the questions raised in the lab are seemingly endless – both Foxe and Freedman attribute that to its collaborative nature. Training levels range from high school students – the lab mentors Rochester City School District students through the NEUROEAST program – to 5th-year graduate students – some of whom go on to become postdoctoral fellows in the lab.

"Working in a large lab means having the opportunity to work independently, which has made me more selfsufficient and confident in my field of interest. Moreover, this environment is very collaborative and can be viewed as a "hive-mind", where ideas and knowledge are regularly shared among students and investigators from a variety of disciplines. This is the attribute that has been absolutely pivotal to my success as a neuroimaging researcher and has drastically improved the way I address scientific questions

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and the community,” said Kathryn Toffolo, a rising fifth year in the Neuroscience Graduate Program. Her research uses EEG and fMRI to study auditory language development in children with and without autism spectrum disorder. “It has also given me the opportunity to develop my scientific communication by teaching incoming high school, undergraduate, and Ph.D. students about my research and how to conduct a proper experiment. I am very happy to say that my experience at the CNL has positively changed how I interact with the world and

has paved the way for a successful career.”

“Early in my career, I decided not to constrain myself to one problem. I have an appetite for science and knowledge, and being able to have great students and faculty in the lab with a drive to know more has allowed the lab to become more of a co-op,” said Foxe. “This also makes way for more inclusion at the bench which is imperative for the future success of science.”

Kathryn Toffolo, a rising fifth year in the Neuroscience Graduate Program, gives a talk at the Schindler lab dedication event. (May 2022)

Foxe explains task to participant inside the EEG booth in the CNL.

From left: Sophie Glover, Marion A. Schindler, Frederick J. Schindler, Ph.D. (B.S. '57), Mark Taubman, M.D., Ed Freedman, Ph.D., John Foxe, Ph.D., stand together at event to rename the CNL to the Frederick J. and Marion A. Schindler Cognitive Neurophysiology Laboratory. This renaming ceremony was to thank the Schindlers for their generous philanthropy including setting up the Schindler Autism and High-Density Electrophysiology ABCD Fund and the Fred and Marion Schindler Cognitive Neurophysiology Fund.

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UNIVERSITY OF ROCHESTER | ERNEST J. DEL MONTE INSTITUTE FOR NEUROSCIENCE

NEWS BRIEFS

Major grant funds research to understand key features of OCD: Inflexibility and avoidance A team of scientists from across the country will use a $15.6 million award from the National Institute of Mental Health to investigate the brain networks central to obsessive compulsive disorder (OCD). The five-year grant funds a Silvio O. Conte Center for Basic and Translational Mental Health Research at the University of Rochester. The work will build on more than 15 years of research by lead investigator Suzanne N. Haber, Ph.D., and collaborators to understand the underlying biology of the disease and guide the development of effective treatments.

Heatwole appointed Director of CHeT

Chad Heatwole, M.D., M.S., has been appointed the new director of the Center for Health + Technology (CHeT) at the University of Rochester. Heatwole is a professor of Neurology with a research focus in experimental therapeutics and is sought out by patients from across the country for his expertise in neuromuscular disease and myotonic dystrophy.

CHeT is a recognized leader and innovator in harnessing digital health technologies to study a range of neurological disorders.

Suzanne N. Haber, Ph.D., (right) looks at anatomical samples with members of her lab.

Mriganka Sur, Ph.D., during keynote talk.

Del Monte Institute & UR-IDDRC Symposium: Developmental emergence of neural circuit architecture and function The annual Del Monte Institute for Neuroscience symposium was co-hosted by the University of Rochester Intellectual Developmental Disability Research Center (URIDDRC) in June at the Memorial Art Gallery. Researchers from around the world gave insight into the work underway in their labs. Two highlights of the event were the talks given by the event’s keynote speakers – Beatriz Luna, Ph.D., from University of Pittsburgh and Mriganka Sur, Ph.D., from Massachusetts Institute of Technology.

Beatriz Luna, Ph.D., [second from right] stands with students who recently completed the NEUROEAST program.

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Documentary sheds light on the Parkinson’s ‘pandemic’ A new documentary titled The Long Road to Hope tells the story of individuals with Parkinson’s and efforts to study, treat, and prevent the disease from a global perspective.

The documentary was produced by the University of Rochester Center for Health + Technology (CHeT) and features 12 Parkinson’s patients from the U.S., Canada, the U.K., and the Netherlands, and medical commentary from University of Rochester Medical Center neurologist Ray Dorsey, M.D., and Bas Bloem, M.D., Ph.D., with Radboud University Medical Center in the Netherlands.

WATCH IT TODAY: parkinsontv.org 3498_6/30/22