Many minds, many methods, one brain

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

The 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.

“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.”

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).”

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

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.

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.”

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

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 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

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.

Recreating/replicating real-world experiences in a lab setting is an ongoing challenge. It is a challenge the MoBI 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 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.

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

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 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 (RADx- UP), 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 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.

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.

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

"Working in a large lab means having the opportunity to work independently, which has made me more self sufficient 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 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.”

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.