Neuroscience News from the UR Community

The brain’s complex network of neurons enables us to interpret and effortlessly navigate and interact with the world around us. But when these links are damaged due to injury or stroke, critical tasks like perception and movement can be disrupted. New research is helping scientists figure out how to harness the brain’s plasticity to rewire these lost connections, an advance that could accelerate the development of neuro-prosthetics.

A new study authored by Marc Schieber, M.D., Ph.D., and Kevin Mazurek, Ph.D. with the University of Rochester Medical Center Department of Neurology and the Del Monte Institute for Neuroscience, which appears today in the journal Neuron, shows that very low levels of electrical stimulation delivered directly to an area of the brain responsible for motor function can instruct an appropriate response or action, essentially replacing the signals we would normally receive from the parts of the brain that process what we hear, see, and feel.

“The analogy is what happens when we approach a red light,” said Schieber. “The light itself does not cause us to step on the brake, rather our brain has been trained to process this visual cue and send signals to another parts of the brain that control movement. In this study, what we describe is akin to replacing the red light with an electrical stimulation which the brain has learned to associate with the need to take an action that stops the car.”

Mutated genes present in many patients with congenital heart disease (CHD) are also often found in patients with autism and certain respiratory disorders, according to an extensive analysis of genes from 2,871 congenital heart disease patients and their families, reports the Research@URMC blog.

The research, published last month in the journal Nature Genetics, is the third major publication generated by the Pediatric Cardiac Genomics Consortium (PCGC), a group of 10 centers in the United States and London, including the Medical Center. The center’s goal is to identify genetic causes of CHD.

“It has long been apparent that there is a connection between the developing heart and brain — that patients who have challenges in one area often have challenges in the other — and now we have genetic proof,” says George Porter, associate professor of pediatrics/cardiology and an author of the paper.

The PCGC’s research has enrolled 11,333 patients; Porter and Eileen Taillie, the local study coordinator, have recruited 573 of those patients from the Medical Center and associated pediatric cardiologists in Buffalo and Syracuse. The group conducts a range of genetic tests on selected groups of these patients, with the most significant results thus far coming from whole exome sequencing on more than 3,000 patients with complex CHD and their families. The ongoing project represents the most robust genetic analysis ever performed on patients with CHD, which affects about 1 percent of babies.

“Clinically, this is the next step toward a more personalized approach for patients with CHD,” says Porter. “One possibility: you could potentially create a panel of genes to test in patients with CHD, and if you find one that also affects learning, for example, you could intervene earlier.”

The paper’s co-senior authors are Martina Brueckner of the Yale School of Medicine and Christine Seidman of Harvard Medical School.

Krishnan Padmanabhan, Ph.D.

Congratulate Krishnan on receiving one the this year's NIMH 2017 BRAINS awards.

The NIMH Biobehavioral Research Awards for Innovative New Scientists (BRAINS) award is intended to support the research and research career advancement of outstanding, exceptionally productive scientists who are in the early, formative stages of their careers and who plan to make a long term career commitment to research in specific mission areas of the NIMH. This award seeks to assist these individuals in launching an innovative clinical, translational, basic or services research program that holds the potential to profoundly transform the understanding, diagnosis, treatment, or prevention of mental disorders. The NIMH BRAINS program will focus on the research priorities and gap areas identified in the NIMH Strategic Plan and the Research Domain Criteria (RDoC) project.

Stephen Steadman '64, center, presents Kevin Mazurek, left, with the first place honor and audience prize at the Meliora Weekend competition for the Steadman Family Postdoctoral Associate Prize in Interdisciplinary Research. Steadman, who received a BS in physics from the University of Rochester, is a scientific administrator at the Laboratory for Nuclear Science and the Department of Physics at MIT. Melissa Sturge-Apple, dean of graduate studies, is at right. (University of Rochester photo / Bob Marcotte)

Even simple movements require the integration of information from multiple areas of the brain. This process breaks down when brain damage occurs, resulting in neurological disorders.

But what if researchers could find a way to bypass those damaged areas and maintain the flow of information?

Kevin Mazurek, a postdoctoral fellow in the lab of Marc Schieber, professor of neurology, described how the lab is making progress in doing just that. He finished in first place and took the audience prize as well in the Meliora Weekend competition for the Steadman Family Postdoctoral Associate Prize in Interdisciplinary Research.

Mazurek’s prizes were worth $1,250.

Using micro electrical stimulation in primates, “we’ve shown that we can deliver the information successfully to two functionally different areas of the brain,” Mazurek explained. “This is an important first step.”

The next steps in the research, which incorporates neurology, neuroscience, electrical engineering, and biomedical engineering, include expanding the ability to communicate information across a wide reach of brain areas. This could “potentially improve the quality of living for individuals with injuries such as stroke, traumatic brain injury, or Alzheimer’s disease.”

This is the second year of the competition.

It is open to all postdoctoral scholars and appointees in the School of Medicine and Dentistry, and in Arts, Sciences & Engineering. Four prizes are awarded for research that exemplifies the importance of cross- disciplinary approaches toward examining high impact questions of science. Prizes were awarded based on 3-minute oral presentations to a panel of judges.

This year’s topics ranged from “Recent Breakthroughs in Understanding the Brain’s Waste Removal System” to “Catalytic Solar-Driven Generation of H2 in Artificial Photosynthesis” – and the benefits of yoga in helping cancer patients cope with the side affects of chemotherapy.

Complex, multi-system diseases like Parkinson’s have long posed challenges to both scientists and physicians. University of Rochester Medical Center (URMC) researchers are now reaching for new tools, such as algorithms, machine learning, computer simulations, and mobile technologies, to both improve care and identify new therapies.

Parkinson's disease is a progressive neurological disorder that erodes an individual’s control over their movements and speech. While many of the recent advances in treatment have transformed Parkinson’s into a manageable chronic illness, the individual patient experience can vary widely in both the onset and progression of the symptoms of the disease. This creates problems for clinicians who must constantly tweak the combination and doses of medications to effectively manage symptoms and researchers who are often confronted with a range of responses to experimental treatments.

The advent and spread of new technologies – such as to broadband internet, smartphones, and remote monitoring and wearable sensors – coupled with growing investments in computational resources and expertise in fields such as bioinformatics and data science have the potential to provide researchers with unprecedented insight into the complex variations of diseases like Parkinson’s.

An example of this approach is new research out in the journal The Lancet Neurology. The study sought to identify genetic markers that may explain why motor symptoms –stiffness or rigidity of the arms and legs, slowness or lack of movement, tremors, and walking difficulties – come on more rapidly for some patients with the disease.

The research involved Charles Venuto, Pharm.D., an assistant professor in the URMC Department of Neurology and the Center for Health + Technology (CHeT), and GNS Healthcare, and was funded by the Michael J. Fox Foundation for Parkinson’s Research and the National Institute of Neurological Disorders and Stroke.

The researchers tapped into huge data sets compiled by the Parkinson’s Progression Markers Initiative (PPMI) which has collected biological samples and clinical data from hundreds of individuals with the disease.

“We have access to more information about diseases like Parkinson’s than ever before,” said Venuto. “But all of that data has created a scientific conundrum akin to losing sight of the forest for the trees. In order to unlock the potential of this information we need to harness more sophisticated ways to understand what we are seeing.”

In a departure from traditional research approaches, the team turned over the vast quantities of genetic, clinical, and imaging profiles compiled by the PPMI study to a machine learning and simulation program. As the computer program analyzed the data, it was also “learning” by constantly refining and modifying its criteria and algorithms as it sifted through the information looking for patterns and associations.

The study identified a mutation in the LINGO2 gene that, together with a second gene and demographic factors, could identify patients with faster motor progression of Parkinson’s. The finding, if confirmed, could ultimately help clinicians refine care and help researchers more precisely understand how individual patients may respond to experimental therapies.

The application of data-driven technologies to biomedical research has exploded in the last several years. URMC neurologist Ray Dorsey, M.D., M.B.A., who is also the director of CHeT, has been at the forefront of this transformation. Dorsey has long been a pioneer in expanding access to Parkinson’s care via telemedicine.

Can a workout regimen for your mind and body help to fend off Alzheimer’s disease?

Physical and mental activity have been shown to boost brain function in different ways, but a new study will look to see if the benefits of engaging in a rigorously designed program that includes both aerobic exercise and brain training will complement each other, producing greater gains in cognition than if both activities had been done independently.

Feng Vankee Lin, Ph.D., R.N., assistant professor in the University of Rochester School of Nursing, the Departments of Neuroscience, Brain and Cognitive Sciences, Neurology, and Psychiatry, and director of the Cog-T Laboratory promoting successful aging, and Fang Yu, Ph.D., R.N., G.N.P.-B.C., F.G.S.A., F.A.A.N., associate professor at the University of Minnesota School of Nursing, are principal investigators on the five-year, $3.67 million grant from the National Institute of Aging.

“This is the first trial to test the synergistic effects of a combined program of aerobic exercise and cognitive training on cognition and mechanisms relevant to Alzheimer’s disease-associated neurodegeneration in older adults with mild cognitive impairment,” said Lin.

URMC Drug to be Tested for Delirium and Dementia Following Surgery; Also Brain Disorder ALS

For those caring for elderly parents or grandparents, this scene may be familiar: Grandma falls and fractures her hip. Grandma has surgery to repair the broken hip. Grandma comes out of surgery delirious and confused; she can’t remember simple things, or focus on more than one thing at a time.

More than half of older adults suffer from delirium after surgery that may progress to dementia, a condition called postoperative cognitive dysfunction (POCD). There are no good treatments for postoperative cognitive dysfunction, which is associated with increased illness and death. Estimates suggest that caring for patients with POCD costs more than $150 billion a year.

A team of researchers from the University of Rochester Medical Center (URMC) and Duke University Medical Center is addressing the problem, with the help of a five-year, $2.8 million grant from the National Institutes of Aging at the National Institutes of Health.

What causes postoperative cognitive dysfunction?

What causes postoperative cognitive dysfunction is not entirely understood, but the body’s immune response to surgery and subsequent inflammation throughout the body – including in the brain – likely play a role. The team, led by Niccolo Terrando, Ph.D. at Duke, will test in animal models a drug developed in the laboratory of Harris A. “Handy” Gelbard, M.D., Ph.D. at URMC. Called URMC-099, the drug tamps down the body’s immune response and reduces inflammation.

A new study published in the journal Brain Behavior and Immunity appears to challenge the theory that cells in the brain’s immune system are the culprit behind the neurological damage that occurs in children exposed to alcohol while in the womb.

“In order to develop treatments for this condition, we must first understand how alcohol affects the developing brain,” said Ania Majewska, Ph.D., an associate professor in the Department of Neuroscience at the University of Rochester Medical Center (URMC) and lead author of the study. “While the hypothesis that dysfunctional immune cells play a role in fetal alcohol syndrome is logical and enticing, it appears that this idea may be a scientific dead end.”

Exposure to alcohol in the womb can lead to fetal alcohol spectrum disorders (FASD), a condition that causes lifelong physical and cognitive impairments, and for which there is no available treatment. The symptoms suffered by individuals with FASD can range from poor impulse control and attention, learning disabilities, compromised fine motor skills, and delays in the ability of the brain to process visual and auditory information. FASD is diagnosed in about one out of every 100 babies born in the U.S.

New research will seek to understand why people who are HIV positive are more susceptible to a progressive cerebrovascular disease that can ultimately give rise to dementia. One of the goals of the research is to identify new ways to prevent the blockages that occur in blood vessels and cause damage in the brain.

The $3.6 million National Institute of Aging-sponsored study will be led by University of Rochester Medical Center (URMC) neurologist Giovanni Schifitto, M.D., M.S., and Sanjay B. Maggirwar, M.B.A., Ph.D., with the Department of Microbiology and Immunology.

While it is estimated that more than 1 million Americans are living with HIV, treatments such as combined anti-retroviral therapies (cART) have transformed the disease into a manageable chronic illness. However, as the population living with HIV ages, the long-term effects of both the infection and treatment have given rise to additional health problems.

One such problem is cerebral small vessel disease (CSVD). While the reason CSVD occurs is not clear and may ultimately be the result of a number of factors, a common mechanism is believed to be inflammation. The new study will examine the interaction of two types of blood cells – platelets and monocytes. When these cells become stuck together and form complexes the resulting blockages can lead to a hardening of the arteries.

The brain in particular is highly susceptible to damage when blood flow becomes impaired due its network of tiny vessels. When complexes of platelets and monocytes accumulate in the brain they can promote inflammation which can cause vessels to become leaky, plugged, or burst, resulting in micro-strokes or micro-hemorrhages that damage neurons and other tissue in the brain.

The University of Rochester Medical Center (URMC) is participating in what is being characterized as the largest long-term study of brain development and child health. The study will follow the biological and behavioral development of more than 10,000 children from ages 9-10 through early adulthood.

The Adolescent Brain Cognitive Development (ABCD) Study was created by the National Institutes of Health to evaluate the developmental period during which the brain undergoes dramatic changes. The study will seek to better understand how children's experiences impact brain maturation and other aspects of their lives, including academic achievement, social development, behavior, and overall health.

"Adolescence is a time of extraordinary physical, emotional, and intellectual growth," said John Foxe, Ph.D., director of the Del Monte Neuroscience Institute and principal investigator of the URMC ABCD Study. "Yet there is a great deal that we don't know about how experiences such as participation in sports or music programs, screen time, sleep patterns, and long-term exposure to medications and stimulants impact their transition to adulthood."

The Microglial Fractalkine Receptor is not Required for Activity-Dependent Plasticity in the Mouse Visual System

Microglia have recently been implicated as key regulators of activity-dependent plasticity, where they contribute to the removal of inappropriate or excess synapses. However, the molecular mechanisms that mediate this microglial function are still not well understood. Although multiple studies have implicated fractalkine signaling as a mediator of microglia–neuron communications during synaptic plasticity, it is unclear whether this is a universal signaling mechanism or whether its role is limited to specific brain regions and stages of the lifespan. Here, we examined whether fractalkine signaling mediates microglial contributions to activity-dependent plasticity in the developing and adolescent visual system. Using genetic ablation of fractalkine's cognate receptor, CX3CR1, and both ex vivo characterization and in vivo imaging in mice, we examined whether fractalkine signaling is required for microglial dynamics and modulation of synapses, as well as activity-dependent plasticity in the visual system. We did not find a role for fractalkine signaling in mediating microglial properties during visual plasticity. Ablation of CX3CR1 had no effect on microglial density, distribution, morphology, or motility, in either adolescent or young adult mice across brain regions that include the visual cortex. Ablation of CX3CR1 also had no effect on baseline synaptic turnover or contact dynamics between microglia and neurons. Finally, we found that fractalkine signaling is not required for either early or late forms of activity-dependent visual system plasticity. These findings suggest that fractalkine is not a universal regulator of synaptic plasticity, but rather has heterogeneous roles in specific brain regions and life stages.

Ross Maddox, PhD

Ross Maddox's lab has posted the preprint for his latest paper on biorXiv! They showed that it's possible to measure the response of the auditory brainstem to natural speech using EEG.

Speech is an ecologically essential signal whose processing begins in the subcortical nuclei of the auditory brainstem, but there are few experimental options for studying these early responses under natural conditions. While encoding of continuous natural speech has been successfully probed in the cortex with neurophysiological tools such as electro- and magnetoencephalography, the rapidity of subcortical response components combined with unfavorable signal to noise ratios has prevented application of those methods to the brainstem. Instead, experiments have used thousands of repetitions of simple stimuli such as clicks, tonebursts, or brief spoken syllables, with deviations from those paradigms leading to ambiguity in the neural origins of measured responses. In this study we developed and tested a new way to measure the auditory brainstem response to ongoing, naturally uttered speech. We found a high degree of morphological similarity between the speech-evoked auditory brainstem responses (ABR) and the standard click-evoked ABR, notably a preserved wave V, the most prominent voltage peak in the standard click-evoked ABR. Because this method yields distinct peaks at latencies too short to originate from the cortex, the responses measured can be unambiguously determined to be subcortical in origin. The use of naturally uttered speech to evoke the ABR allows the design of engaging behavioral tasks, facilitating new investigations of the effects of cognitive processes like language processing and attention on brainstem processing.

A new $3.2 million grant will bring together biomedical scientists and mechanical engineers in an effort to develop a detailed understanding of the brain's waste removal system. The research could have significant implications for diseases like Alzheimer's that arise when this system breaks down and toxic proteins accumulate in the brain.

The new research is being funded by the National Institute on Aging and will study the glymphatic system. This system is unique to the brain and was first described by Maiken Nedergaard, M.D., D.M.Sc., the co-director of the University of Rochester Center for Translational Neuromedicine, and her colleagues in 2012, who showed how cerebral spinal fluid (CSF) is pumped into brain tissue and flushes away waste. Subsequent research has shown that the glymphatic system is more active while we sleep and can be damaged by stroke and trauma.

Maybe you've recently suffered a stroke and are now starting therapy, trying to regain speech, motor functions, and possibly improve memory. But your vision is damaged, too, and there's no therapy available.
Yet.
Krystel Huxlin, director of research and the James V. Aquavella Professor of Ophthalmology at the University of Rochester Medical Center's Flaum Eye Institute, has been working in her lab over the last ten years to change that. Here's how she sums up her latest results, published earlier this year in the journal Neurology:

"If people do exactly what we tell them and they don't cheat, the success rate has been in our hands a 100 percent."

Huxlin spoke at the inaugural Light & Sound Interactive conference in Rochester, jointly sponsored by the University of Rochester and the Rochester Institute of Technology, as part of a panel on blindness and visual impairment that addressed corrective, restorative and rehabilitative approaches.

Dan Fabbio was 25 and working on a master's degree in music education when he stopped being able to hear music in stereo. Music no longer felt the same to him.

When he was diagnosed with a brain tumor, he immediately worried about cancer. Fortunately, his tumor was benign. Unfortunately, it was located in a part of the brain known to be active when people listen to and make music.

Fabbio told his surgeon that music was the most important thing is his life. It was his passion as well as his profession.

His surgeon understood. He's someone whose passion has been mapping the brain so he can help patients retain as much function as possible.

Dr. Web Pilcher, chair of the Department of Neurosurgery at the University of Rochester Medical Center, and his colleague Brad Mahon, a cognitive neuroscientist, had developed a brain mapping program. Since 2011, they've used the program to treat all kinds of patients with brain tumors: mathematicians, lawyers, a bus driver, a furniture maker. Fabbio was their first musician.

The idea behind the program is to learn as much as possible about the patient's life and the patient's brain before surgery to minimize damage to it during the procedure.

"Removing a tumor from the brain can have significant consequences depending upon its location," Pilcher says. "Both the tumor itself and the operation to remove it can damage tissue and disrupt communication between different parts of the brain."

Ahead of Fabbio's surgery, it was important to understand exactly what parts of his brain were responsible for his musical abilities. The team spent six months studying the functional and structural organization of Fabbio's brain, Mahon tells All Things Considered host Robert Siegel.

Researchers from the University of Rochester Medical Center recently set out to understand whether drugs used to keep HIV patients alive could be damaging their brains.  On the contrary, early results from their clinical study showed that short-term use of combination anti-retroviral therapy (cART) improved mental function in HIV-infected individuals. 

Giovanni Schifitto, M.D., M.S., professor of Neurology at the University of Rochester Medical Center, is leading the study to better understand the short and long term effects of combination antiretroviral therapy on HIV patients’ brains. At 12 weeks, the therapy appears to improve mental performance and functional connectivity in the brain.

HIV patients often experience mental decline ranging from mild impairment to full-blown dementia. Experts have long debated the cause of that mental decline: HIV itself, or the drug used to combat it.

Some of the first HIV drugs were known to cause damage to peripheral nerves. Newer anti-retroviral drugs are believed to be safer, but patients taking these drugs continue to experience mental impairment - even when their viral load is extremely low.  In fact, some studies have shown improvement in HIV patients’ mental function when they stop using cART.

“But those studies were very indirect,” said Schifitto, who is also the director of the Clinical Research Center and function leader for Participant and Clinical Interactions at the CTSI. “They studied cohorts of people who were already on medications, which makes it very hard to pull apart whether the virus or the drug is to blame for effects in the brain.”

Schifitto’s clinical study, on the other hand, followed 17 HIV-infected individuals who had not received any treatment prior to the study. These patients scored worse on mental function tests and brain imaging revealed fewer connections in their brains than the HIV-negative control group.

After receiving cART for 12 weeks, the HIV patients’ mental performance and functional brain connectivity improved nearly to the level of the HIV-negative group. This not only suggests that short term cART use does not damage the brain, but that the virus is the culprit for early mental impairment in HIV-infected patients.

However, this is just a first step of the study, which will enroll and follow over 150 participants for two years. It is possible that cART will cause mental decline after prolonged use and the team want to track if and when that happens.  They are also monitoring sleep, mood, and several other factors that can impact mental function in HIV patients taking cART. 

In the end, the outcomes of the short and long term studies may help health care providers tailor cART cocktails and treatment schedules to individual patients’ needs. The results could also have implications for preventative use of cART in individuals who are at high risk for contracting HIV, a practice called pre-exposure prophylaxis (PrEP).

The study started with just a single site at the University of Rochester Medical Center, but now includes sites at Cornell Medical Imaging Center, Gay Men’s Health Crisis, SUNY Upstate Medical, University at Buffalo, and University of Texas Health Science Center at Houston.  It also utilized the CTSI’s Clinical Research Center, a dedicated space for researchers to conduct safe and controlled clinical studies with the support of highly trained clinical research staff.

“Researchers have long fixed their attention on eye-tracking in detecting autism spectrum disorders, but now they may have discovered a new tool that could lead to earlier diagnosis and intervention.” the research is by John Foxe, the Kilian J. and Caroline F. Schmitt Professor in Neuroscience and chair of the Department of Neuroscience.

In a July 12 article in the European Journal of Neuroscience, researchers at the University of Rochester linked differences in the cerebellar vermis (in the rear of the cerebellum, which controls the development of human movement, social skills and emotional development) to the plasticity of saccadic or rapid eye movements within a subgroup of people with disorders on the autism spectrum (ASD).

Rapid eye movements (also known as saccade) may be the key, say Edward G. Freeman, Ph.D., and John J. Foxe Ph.D. These eye movements-typically quick, precise and accurate in healthy eyes-occur when we shift our gaze between objects and are important in interacting with the world. Sometimes though, in people with ASD, the movements can "over- or undershoot the intended target locations," they wrote in the study.

Strong Memorial Hospital’s Neurology and Neurosurgery specialty program has been ranked among the top 50 in the nation for 2017-2018 by U.S. News & World Report. The program ranked 39^th among the nation’s hospitals, and this is the seventh consecutive year it has been nationally ranked by U.S. News.

In June, UR Medicine’s Golisano Children’s Hospital was recognized as one of the nation’s best children’s hospitals in three specialty areas — Neonatology, Nephrology, and Neurology and Neurosurgery — in the U.S. News & World Report’s Best Children’s Hospital rankings.

For the 2017-18 adult rankings, U.S. News evaluated more than 4,500 U.S. hospitals; only 152 were ranked in at least one specialty.

Eight Strong Memorial Hospital specialty programs earned High Performing ratings: Cardiology and Heart Surgery, Diabetes and Endocrinology, Gastroenterology and GI Surgery, Geriatrics, Nephrology, Orthopaedics, Pulmonology, and Urology.

U.S. News recognized hospitals that were high-performing across multiple areas of care and ranked them within their states and by metropolitan areas. U.S. News rated Strong Memorial as the top hospital in the Rochester Metro area and fourth among New York state hospitals.

U.S. News evaluates nearly 5,000 hospitals nationwide for its Best Hospitals rankings; methodologies include objective measures such as patient survival, the number of times a given procedure is performed, infection rates, adequacy of nurse staffing and more.

Errant glia may underlie childhood-onset schizophrenia illness process

At least some cases of schizophrenia may be caused by an illness process rooted in wayward support cells instead of the neurons they sustain, suggest experiments by NIMH-funded researchers. Such glial cells, generated – via a disease-in-a-dish technology – from patients with childhood onset schizophrenia, stunted neural circuit development when grafted into developing mouse brains. The animals grew up to display anxiety-like behaviors, antisocial tendencies, sleep-disturbances, and a lack of motivation, mimicking some features of the human illness.

NIMH grantee Steven Goldman, M.D., Ph.D., of the University of Rochester, and colleagues, report on their findings in the August 3, 2017 issue of Cell Stem Cell. An accompanying editorial heralds their discovery as “one of the most creative and compelling uses of stem cell technology for disease modeling” – with potential implications for improved treatments.

Although evidence was mounting of glial-related abnormalities in schizophrenia prior to the new study, researchers didn’t know whether these might just be secondary to a neuron-rooted illness process. Animal models to sort this out were lacking, so Goldman and his team set out to develop one. They generated induced pluripotent stem cells (iPSCs) from skin cells of patients who had experienced onset of psychosis before puberty. While rare, such cases of childhood onset schizophrenia are thought to be more genetically-influenced and severe than more typical cases with onset in late adolescence or early adulthood.

Michael Tanenhaus, the Beverly Petterson Bishop and Charles W. Bishop Professor of Brain and Cognitive Sciences, is this year’s recipient of the prestigious David E. Rumelhart Prize, the premier award in the field of cognitive science. He accepted the award at the annual meeting of the Cognitive Science Society last week.

The prize, which includes a $100,000 monetary award, has been bestowed annually since 2001 to an individual or team making a significant contribution to the theoretical foundations of human cognition.

Over the course of his 40-year career, Tanenhaus has focused his research on the mechanisms underlying spoken language and reading comprehension. He is best known as the creator of the Visual World Paradigm, which uses eye movements to study the mechanisms behind speech and language comprehension. This paradigm has been widely adopted for studying language development and disorders.

Below, Tanenhaus discusses this award and his research in his own words:

To use the English expression, I was gobsmacked to learn I had been awarded the Rumelhart Prize. The previous winners have been giants in cognitive science from multiple disciplines, so it’s humbling to be considered worthy.

All of my influential work was conducted in collaboration with a remarkable group of graduate students and post-docs who flowed through the lab as well as collaborations with [University of Rochester professors] Dick Aslin and Greg Carlson, among others. I can take credit for the body of work. However, for every important step there were talented students who led the way. Consider the development of the Visual World Paradigm, a method where we monitored eye-movements using a head-mounted eye-tracker, while participants followed instructions to manipulate objects in a workspace or pictures displayed on a screen. This paradigm allowed us to ask questions about spoken language processing that ranged from speech perception to interactive conversation, widening the domains of inquiry, and revealing important properties of natural language processing. Students led these projects. Their projects formed the initial foundation for their research programs, and pioneered application of the paradigm to new areas of inquiry within language processing.

At the same time, the award is a Rochester story. My work took place in a remarkable interdisciplinary community in cognitive science and later the language sciences that spanned multiple departments, including linguistics, computer science and BCS. The communities created a culture of collaboration, joint mentoring of students, and synergy among research programs that attracted exceptional students and encouraged innovative interdisciplinary research.

Newly appointed Dept. of Neuroscience faculty member, Farran Briggs, Ph.D. has her research highlighted on Wired.

When ferrets get a rabies shot in a neurobiology lab, they don't get infected with the virus—or even inoculated against it. They get a brain hack that might just explain how your brain handles vision, and maybe even your other senses, too.

In a lab at Dartmouth, scientists are experimenting with targeted injections of a modified rabies virus into the brains of ferrets—essentially allowing them to control how the animal responds to simple visual patterns. The goal is to understand the brain's enormously complex visual processing system. But really? Rabies? Ferrets? Are these guys just screwing around?

Lots of visual research depends on lab mice—the most popular of model organisms in biology. But Dartmouth neuroscientist and lead author Farran Briggs wanted to study an animal that uses its vision the same way humans do, in an evolutionary sense: to prey on tasty snacks. Mice aren’t predators, and their vision falls solidly in the ‘legally blind’ range. So these vision researchers turned to the notoriously vicious ferret and its front-facing eyes. They're color blind, but at the neural level, ferrets’ visual systems have “remarkable similarities to a primate, and a human,” says Briggs. (Ferrets also help avoid the ethical issues of experimenting on primates.)

A new study out in European Journal of Neuroscience could herald a new tool that helps physicians identify a sub-group of people with Autism spectrum disorders (ASD). The test, which consists of measuring rapid eye movements, may indicate deficits in an area of the brain that plays an important role in emotional and social development.

“These findings build upon a growing field of research that show that eye movement could serve as a window into a part of the brain that plays a role in a number of neurological and development disorders, such as Autism,” said John Foxe, Ph.D., director of the University of Rochester Medical Center Del Monte Neuroscience Institute and co-author of the study.

ASD is characterized by a wide range of symptoms that can vary in severity from person to person. This unpredictability not only presents a challenge for diagnosis, but also how best to devise a course of treatment. Identifying the specific phenotype of the disorder is, therefore, an essential first step to providing effective care.

Astrocytes help coordinate communication
between neurons. The one on the left is
derived from a healthy brain and the one on
the right is from an individual diagnosed
with schizophrenia.

New research has identified the culprit behind the wiring problems in the brains of people with schizophrenia. When researchers transplanted human brain cells generated from individuals diagnosed with childhood-onset schizophrenia into mice, the animal’s nerve cell networks did not mature properly and the mice exhibited the same anti-social and anxious behaviors seen in people with the disease.

“The findings of this study argue that glial cell dysfunction may be the basis of childhood-onset schizophrenia,” said University of Rochester Medical Center (URMC) neurologist Steve Goldman, M.D., Ph.D., co-director of the Center for Translational Neuromedicine and lead author of the study which appears today in the journal Cell. “The inability of these cells to do their job, which is to help nerve cells build and maintain healthy and effective communication networks, appears to be a primary contributor to the disease.”

The National Institutes of Health has awarded a grant to URMC researchers exploring methods of making cognitive training more effective for older adults by improving their attitudes toward computers.

Feng Vankee Lin, Ph.D., RN, an SON assistant professor and director of the CogT Lab promoting successful aging, and Benjamin Chapman, Ph.D., MPH, associate professor of Psychiatry, are principal investigators on the $421,000, two-year study.

Computerized cognitive training methods, such as online “brain games” have been widely implemented among adults with mild cognitive impairment (MCI) in recent years. However those interventions have not proven to be a consistently reliable method of improving or maintaining the cognitive health of older adults. Results are highly variable, and one possible explanation lies in how comfortable seniors feel using technology.

“The goal of this study is to generate a proof-of-concept for an intervention that may improve attitudes toward computers among those older adults with MCI,” said Lin, who is now principal or co-investigator on six current NIH grants. “Improving the intervention engagement of those individuals, we think, will then help us develop more effective computerized cognitive interventions in the future. It is the first study that we know of that strives to augment computerized cognitive training by addressing an attitudinal or affective element of the person.”

At the core of the study is the notion of person-centered care – integrating individuals’ preference throughout the process of intervention. The person-centered approached has been shown to improve engagement among older persons, including those with MCI, and pilot data collected at assisted-living facilities suggests that computer-led leisure activities promotes psychological well-being among older persons with MCI and may change their perception about technology. A computer used for fun activities may no longer seem daunting, complex, or irrelevant, but instead be seen as familiar and enjoyable.

“These results are consistent with a number of theories indicating that exposure to pleasurable experiences with an object or task improves several dimensions of attitudes, including affective and cognitive components, as well as behavior and motivation,” Lin said.

Grounded in this pilot data and the theory around it, investigators will lead a small randomized controlled trial among assisted-living residents to assess whether a period of computer-led leisure activities prior to cognitive training improves attitudes toward computers, engagement with the intervention, or cognitive outcomes.

Anton Porsteinsson, M.D., professor of Neurology, is a co-investigator on the grant, which is also receiving recruitment support from Dallas Nelson, M.D., and Sarah Howd, M.D., in the Department of Medicine’s Division of Geriatrics and Aging.

The American Heart Association/American Stroke Association (AHA/ASA) has once again honored the UR Medicine Strong Memorial Hospital as having met its highest standards of care for stroke.

Strong Memorial Hospital has received the AHA/ASA Get With The Guidelines program’s Stroke Gold Plus Quality Achievement Award. The hospital was also tapped for the Target: Stroke Honor Role Elite Plus, which recognizes hospitals that have consistently and successfully reduced door-to-needle time – the window of time between a stroke victim’s arrival at the hospital, the diagnosis of an acute ischemic stroke, and the administration of the clot-busting drug tPA. If given intravenously in the first three hours after the start of stroke symptoms, tPA has been shown to significantly reduce the effects of stroke and lessen the chance of permanent disability.

“This recognition is a testament to the hard work of our outstanding team of nurses, physicians, and therapists and their dedication to provide the highest quality of care to stroke victims,” said neurologist Curtis Benesch, M.D., M.P.H., the medical director of the UR Medicine Comprehensive Stroke Center.

“This award reflects a singular focus on improving the care stroke victims receive from the first 911 call to when they arrive at the hospital through operating room, neurocritical care, and rehabilitation,” said Tarun Bhalla, M.D., Ph.D., the surgical director of the Comprehensive Stroke Center.

Strong Memorial Hospital is home to the region’s only Comprehensive Stroke Center, a designation by the Joint Commission that indicates that the hospital either meets or exceeds the highest standards of care required to provide timely and comprehensive care to patients with complex cerebrovascular disease.

The AHA/ASA Get With the Guidelines program recognizes hospitals that have reached aggressive goals of treating stroke patients and comply with core standard levels of care. For more information about the Get With The Guidelines program, visit the AHA/ASA website.

A new study shows that patients with low back pain who were depressed were more likely to be prescribed opioids and receive higher doses. Understanding these prescribing patterns sheds new light on the current opioid epidemic and may help determine whether efforts to control prescription opioid abuse are effective.

“Our findings show that these drugs are more often prescribed to low back pain patients who also have symptoms of depression and there is strong evidence that depressed patients are at greater risk for misuse and overdose of opioids,” said John Markman, M.D., director of the Department of Neurosurgery’s Translational Pain Research Program at the University of Rochester Medical Center (URMC) and senior author of the study which appears in PAIN Reports, a journal of the International Association for the Study of Pain.

Low back pain is a leading cause of disability in the U.S., the most common condition for which opioids are a prescribed treatment.

Using data from the Medical Expenditure Panel Survey, a federally-compiled set of large-scale surveys of families and individuals, their medical providers, and employers across the U.S., the researchers compiled opioid prescription data from 2004-2009.

Ed Freedman and John Foxe have just published preliminary data from a study examining eye movement changes in individuals with Autism Spectrum Disorders (ASD), particularly looking at the role of the cerebellum (DOI: 10.1111/ejn.13625). The cerebellum, Latin for ‘little’ brain, sits at the base of brain, underneath the cerebral cortex. Although it has been called ‘mini’, the cerebellum actually has more neurons, or cells, than the cerebral cortex. Classically considered to play a role in the control of movements and the learning of motor patterns, it is now known to play a role in emotion and cognition through its connection to the rest of the brain. And, there is evidence that the structure of the cerebellum is altered in a sub-population of individuals with ASD.

In the current paper, Ed and John present the results of experiments tracking the rapid eye-movements made when looking from one object to another, or saccades, in individuals with ASD. Accuracy and precision are maintained by careful comparison of the movement command produced by the brain and the results of the actual movement. Any differences between these lead to adjustments of the commands for ensuing saccades. This type of sensorimotor adaptation is dependent on the proper functioning of the cerebellum. However, there is anatomical evidence that some people with an ASD have cerebella with slightly altered structure. If the cerebellar structure is altered, is its function also altered in this sub-group of people? Assessing the ability of people with an ASD to adapt saccade amplitudes is one way to determine whether this function of the cerebellum is altered in ASD.

Another point of interest is determining if the deficits in saccades relate to any of the other key symptoms observed in ASD.

If saccade adaptation deficits do turn out to be a consistent finding in a sub-group of children with ASD, this raises the possibility that saccade adaptation measures may have utility as an early-detection endophenotype. Changes in cerebellar structure most likely occur in utero and very recent work has shown that saccadic adaptation can be measured in children as young as 10-41 months of age is a most encouraging development indeed. - Ed and John

University of Rochester Medical Center researchers have discovered that loss of muscle stem cells is the main driving force behind muscle decline in old age in mice. Their finding challenges the current prevailing theory that age-related muscle decline is primarily caused by loss of motor neurons. Study authors hope to develop a drug or therapy that can slow muscle stem cell loss and muscle decline in the future.

A program called Parkinson's Disease Care New York exists to help eliminate the obstacles facing patients who need to see a neurologist. This type of doctor can mainly be found in large metropolis areas so anyone in a rural community might have a tough time getting access to healthcare.

By linking the patient to the doctor via computer, the neurologist can monitor symptoms more regularly and follow the patient more closely—even diagnose new treatments without the patient even leaving their home. Currently 109 patients are enrolled and the program can provide for 500 people statewide. To find out more, go to the PDCNY Facebook page.

A recent scientific study shows that insufficient amount of sleep leads to the development of Alzheimer's disease. Researchers gain more evidence and are beginning to believe that lack and poor quality of sleep results to the fusion of Amyloids, proteins that bond together to form Alzheimer's plaques.

Dr. Maiken Nedergaard, the lead researcher from the University of Rochester Medical Center, explains the glymphatic system that is present in humans. She says that this system is 10 times more active when in slumber than when awake. The process allows cerebrospinal fluid to flow through spaces around the neurons of people's brains. This a method of purging unwanted proteins (Amyloids) and other wastes into the circulatory system garbage collectors and eventually flushes it out of the body.

In simple terms, Nedergaard explains that the brain has its own sanitation and public works department. It is like a network of sewer facilities mostly done during the brain's nightlife. An example of a housekeeping staff descending to building offices for a cleanup duty to avoid the lumping compound that causes Alzheimer's.

The Center for Neural Development and Disease, led by Harris A. (Handy) Gelbard, M.D., Ph.D., since 2008, will now be the Center for NeuroTherapeutics Discovery, reflecting an increased emphasis on translation and the creation of intellectual property that will lead to new therapies for nervous system disorders.

Gelbard, professor of Neurology, Pediatrics, Neuroscience and Microbiology & Immunology, will continue as director. His research, coupled with the work of Charles Thornton, M.D., professor of Neurology and Neuroscience, and Marc Halterman, M.D., Ph.D., associate professor of Neurology, Neuroscience and Pediatrics, will serve as the anchor of the new center. The trio has a strong track record of grants, publications, and patents, as well as academic and commercial relationships that they are actively pursuing to bring new treatments to the public.

“The Center for NeuroTherapeutics Discovery was developed out of the Center for Neural Development and Disease to create more visibility for academic and commercial partnerships as a necessary bridge for bringing new therapeutics forward,” said Gelbard. “This represents a way to do the best and most cutting edge science possible in a time when the traditional avenues towards funding academic research are changing rapidly.”

The center will bring together many investigators from across the Medical Center and River Campus to identify the mechanisms that lead to various neurological disorders, including HIV-associated neurocognitive disorder (Gelbard lab), myotonic dystrophy (Thornton lab) and stroke (Halterman lab). The center remains committed to its members that investigate the molecular signaling events that lead to nervous system disease during development and aging. Industry partnerships and resources will be sought to fast-track existing therapies or create new molecules that affect these disease mechanisms.

Treatments that harness the immune system to help regenerate damaged cells will be a major focus at the center; the team believes that this approach is broadly applicable to a range of acute and chronic neurodegenerative disorders, such as Parkinson’s disease, multiple sclerosis and Alzheimer’s disease.

Dr. Adam Rouse, Post-doctoral Fellow in Neuroscience, recently received an NIH K99/R00 Pathway to Independence Award from the National Institute of Neurological Disorders and Stroke (NINDS). His project “Neural encoding of motor precision for advancing brain-machine interfaces” will study how motor areas of the brain encode different movements and use advanced mathematical models to build brain-machine interfaces that are more precise and intuitive to the user. In addition to his current mentor, Dr. Marc Schieber, Professor in Neurology and Neuroscience, the award will also support Dr. Rouse’s career development with additional mentoring from Dr. Robert Jacobs, Professor in Brain and Cognitive Sciences, and Dr. Sridevi Sarma, Associate Professor in Biomedical Engineering at Johns Hopkins University.

Elise Kayson, M.S., R.N.C., A.N.P., has been recognized by the Huntington Study Group with its Lifetime Achievement Award for her dedication to seeking treatments that make a difference and improving the quality of life and outcomes for families affected by the disease.

The Huntington Study Group (HSG) is a network of more than 400 investigators, coordinators, scientists, and Huntington's disease experts spread across more than 100 research sites across the globe. HSG brings together patients, families, academic and industry researchers, foundations, and government agencies to seek new treatments that improve the life of individuals with the disease.

Elise continues to be an essential ingredient and role model for the success of the HSG, the many patients and families who we serve, and is a real prize that we celebrate and emulate," said Ira Shoulson, M.D., the founder of the HSG, a former professor of Neurology at URMC, and currently a professor of Neurology at Georgetown University.

Elise's tireless commitment to Huntington's patients and their families and her 20 plus years of experience in pharmaceutical research has been essential to our efforts to develop new ways to treat this devastating disease," said URMC neurologist Ray Dorsey, M.D., M.B.A., chair of the HSG. This award recognizes her dedication and critical role she plays in managing the complex research necessary to bring new drugs to market."

The 2017-2019 Dean’s Teaching Fellows have been named. Beau Abar, Ph.D., assistant professor of Emergency Medicine, has been named the Paul F. Griner Dean’s Teaching Fellow. Jessica Shand, M.D., MHS, assistant professor of Pediatrics, has been named the George L. Engel Dean’s Teaching Fellow. Katherine Greenberg, M.D., assistant professor of Adolescent Medicine and Obstetrics and Gynecology, has been named the Jules Cohen Dean’s Teaching Fellow. Linda Callahan, Ph.D., assistant professor of Neuroscience, has been named the Lawrence E. Young Dean’s Teaching Fellow.

The Dean’s Teaching Fellowship Program is a competitive endowed two-year program for faculty who are dedicated to academic careers in medical education. The mission of the program is to develop faculty who can prepare medical students, residents, and practicing physicians to become professionals who are responsive to society’s needs and the ever-changing health care system.

The program typically accepts four Fellows a year who attend a three-hour, bi-weekly seminar series focused on different areas of educational theory, research and teaching methods, educational technology, assessment, curriculum design, faculty development, leadership and career planning. During their time in the program, Fellows conduct a scholarly educational project that is directly translatable to their teaching role and will culminate in a publication or presentation at a national meeting.

Two University of Rochester start-up companies are among those singled out in a new report from the Science Coalition. The report, “American-Made Innovation Sparking Economic Growth,” identifies 102 companies that trace their roots to federally-funded university research.

“The innovation that drives economic growth in the U.S. is based, in large part, on the scientific discoveries made in research universities and funded by the federal government,” said Rob Clark, University provost and senior vice president for research. “As a nation, it is imperative that we continue to support the fundamental science that leads to new technologies and improves lives.”

Clerio Vision was founded in 2014 by Wayne Knox and Jon Ellis with the Institute of Optics, and Krystel Huxlin with the Flaum Eye Institute in the Medical Center. The company is developing a new technology that improves eyesight by “writing” a prescription on the cornea using small pulses from a laser that change the focusing power of the eye. Because the technique doesn’t change the shape of the cornea like LASIK procedures, it can be repeated as needed over a person’s lifetime to correct vision. The research to develop the technology was funded in part with a $200,000 grant from the National Institutes of Health (NIH).

Recently Dr. Duje Tadin, Associate Professor in Brain and Cognitive Sciences and at the Center for Visual Science won the NARSAD Independent Investigator Award from the Brain and Behavior Research Foundation. The title of his project is "A critical role of perceptual inefficiencies in working memory abnormalities in schizophrenia". He also has a pending application to the Simons Foundation's SFARI Pilot Awards program with a project titled "Functional consequences of elevated internal noise in autism."

Well done!!

Researchers have discovered that a protein implicated in human longevity may also play a role in restoring hearing after noise exposure. The findings, where were published in the journal Scientific Reports, could one day provide researchers with new tools to prevent hearing loss.

The study reveals that a gene called Forkhead Box O3 (Foxo3) appears to play a role in protecting outer hair cells in the inner ear from damage. The outer hair cells act as a biological sound amplifier and are critical to hearing. When exposed to loud noises, these cells undergo stress. In some individuals, these cells are able to recover, but in others the outer hair cells die, permanently impairing hearing. While hearing aids and other treatments can help recovered some range of hearing, there is currently no biological cure for hearing loss.

“While more than a hundred genes have been identified as being involved in childhood hearing loss, little is known about the genes that regulate hearing recovery after noise exposure,” said Patricia White, Ph.D., a research associate professor in the University of Rochester Medical Center Department of Neuroscience and lead author of the study. “Our study shows that Foxo3 could play an important role in determining which individuals might be more susceptible to noise-induced hearing loss.”

New study details "physical therapy" for eyes

DeMay fixes his gaze on a live image of his own eye
in preparation for the next round of training.

Patients who went partially blind after suffering a stroke regained large swaths of rudimentary sight after undergoing visual training designed by researchers at the University of Rochester Medical Center's Flaum Eye Institute.

A new study out today in Neurology®, the medical journal of the American Academy of Neurology, provides the first evidence that rigorous visual training recovers basic vision in cortically blind patients with long-standing stroke damage in the primary visual cortex. Damage to this area of the brain prevents visual information from getting to other brain regions that help make sense of it, causing loss of sight in one-quarter to one-half of an individual's normal field of view. Somewhere between 250,000 and 500,000 people suffer vision loss due to damage to the visual cortex each year.

"We are the only people in the U.S. currently using this type of training to recover vision lost after damage to the primary visual cortex," said study senior author Krystel Huxlin, Ph.D., director of Research and James V. Aquavella, M.D. Professor of Ophthalmology at URMC's Flaum Eye Institute. "If you talk to the majority of clinicians, they still believe nothing can be done."

University of Rochester Medical Center (URMC) researchers were instrumental in the U.S. Food and Drug Administration's (FDA) recent approval of SD-809 (deutetrabenazine) to treat Huntington's disease. Deutetrabenazine is the only the second drug authorized by the agency to treat this rare, inherited neurodegenerative disorder.

The FDA approval was based on results from the First-HD study, a Phase 3 clinical trial which was conducted through the Huntington Study Group (HSG) via a consortium of 34 sites across the U.S. and Canada on behalf of Teva Pharmaceuticals. The study results were published last July in Journal of the American Medical Association.

The URMC Clinical Trials Coordination Center (CTCC) and Department of Biostatistics and Computational Biology -- under the leadership of Elise Kayson, M.S., A.N.P., and David Oakes Ph.D. -- provided scientific, technical, logistical, and analytical support for the First-HD study The CTCC is part of the Center for Human Experimental Therapeutics (CHET) and is a unique academic-based research organization with decades of experience working with industry, foundations, and governmental researchers in bringing new therapies to market for neurological disorders.

Since 1987, the CTCC -- currently directed by Cynthia Casaceli, M.B.A. -- has played a central role in bringing seven new drugs to the market, including pramipexole, entacapone, rasagiline, and rotigitine for Parkinson's, tetrabenezine and deutrabenazine for Huntington's, and dichlorphenamide for periodic paralysis.

"This is a great day for the HD community," said URMC neurologist Ray Dorsey, M.D., M.B.A., chair of the HSG and director of CHET. "The unmet need for therapeutics for individuals with HD is immense, and this approval brings us closer to making HD an increasingly treatable condition."

The First-HD study showed that deutetrabenazine significantly decreased chorea, the involuntary movements that many individuals experience during the course of the disease. Huntington's is an autosomal-dominant, inherited disease that usually causes symptoms in people in their 30s and 40s. In addition to chorea, the disease can cause multiple symptoms, including, cognitive problems, changes in personality, and depression.

"We are very grateful to the patients and families who made this development possible by participating in this ground-breaking trial," said Samuel Frank, M.D., Huntington Study Group's principal investigator for First-HD and associate professor of Neurology at Beth Israel Deaconess Medical Center/Harvard Medical School. "Research participants are the key to bringing new treatments to the entire HD community,"

Claudia Testa, M.D., Ph.D., associate professor of Neurology at Virginia Commonwealth University served as the co-principal investigator of the First-HD study.

Teva Pharmaceuticals is also investigating the potential of deutetrabenazine to treat tardive dyskinesia, a disorder that causes involuntary and repetitive movements, and for tics associated with Tourette syndrome.

New research reveals the complex circuits involved in regulating the neurotransmitter dopamine in our brains. Traditionally thought to be limited to reward seeking, the new study shows that parts of the ‘emotional’ brain may also manipulate dopamine to help us pay attention and react to new information in the environment.

The study, which appears in the journal Neuropsychopharmacology, was led by Julie Fudge, M.D., with the University of Rochester Medical Center (URMC) Department of Neuroscience.

The research focuses on an area of the brain called the amygdala, which is known to be important for social and emotional development and behaviors. The amygdala receives sensory information – sight, sound, and smells – and processes it by combining it with information stored in our memories. It evaluates changes or new information to help determine whether it is worthy of our attention or if it can be ignored. The new study shows that one way the amygdala can accomplish this is by communicating with the brain’s dopamine producing cells.

Professor Edward Brown has received NIH funding for his research project titled, "Using Second Harmonic Generation to Predict Metastatic Outcome in Colon Adenocarcinoma."

"In summary, we previously discovered that an optical scattering phenomenon from primary tumor samples provides an independent prognostic indicator of time to metastasis in colon cancer patients," Professor Brown says. "With this grant we will explore if and how this can be used to improve prediction of outcomes for individual patients, leading to improved therapy decisions."

Abstract:

When treating a colon adenocarcinoma (CA) patient, after surgical resection of the tumor the clinician must formulate a plan for adjuvant systemic therapy. This decision is based upon an assessment of the risk of systemic disease recurrence, and is currently informed by pathological factors such as stage, histological grade, and lymph node status. Improvement of the accuracy of risk assessment for individual patients is an area of recognized need. Much of the current information used to assess risk focuses on the cells within tumors, including their morphological properties. Less attention is paid to the extracellular matrix through which metastasizing cells must travel. Second harmonic generation (SHG) is an optical scattering phenomenon whose directionality (as quantified by the "F/B" ratio) is affected by the diameter, spacing, and disorder of fibrils within collagen fibers. Our preliminary data suggests that F/B analysis of tumor samples provides prognostic information about future metastasis that is "matrix-focused" and hence complementary to current "cell-focused" methods. Consequently we hypothesize that F/B is a clinically useful predictor of metastatic outcome in colon adenocarcinoma. In a preliminary study in 44 Stage I colon adenocarcinoma samples we found that F/B of the primary tumor is a significant prognostic indicator of progression free survival time. Significantly, the quartile of patients with the lowest F/B ratio had a 15 year progression free survival percentage of below 50%. In other words, in this study F/B could identify a subset of Stage I patients who had survival statistics similar to Stage III patients. Stage I patients are rarely prescribed adjuvant chemotherapy while Stage III patients are almost always prescribed it. This suggests that F/B can identify patients who would have benefitted from adjuvant chemotherapy and who were left untreated based upon current prognostic indicators. The prognostic trend was also evident in a cohort of 72 Stage II colon adenocarcinoma samples, although it was not significant. This project will move this idea closer to the clinic by first (Aim 1) using archived samples and follow up data in separate training and validation sets to develop predictive algorithms that include F/B, in addition to clinical and genomic information. Second it will (Aim 2) quantify the effect of adjuvant chemotherapy on the predictive ability of the algorithms, as well as quantify their ability to predict chemotherapeutic efficacy. We predict that F/B analysis will be an effective tool that can reach the clinic rapidly after this study to improve metastatic risk assessment. Improving the accuracy of risk estimation for an individual patient will allow clinicians to treat those patients who are destined for metastases, improving outcomes, while avoiding treatment for those patients who are not, reducing overtreatment.

Alzheimer’s disease claims nearly twice as many American lives annually as it did 15 years ago, according to a new report. “Partly, it is due to increasing numbers of older individuals, partly due to success in treating other leading causes of death, and partly due to increasing awareness that AD [Alzheimer’s] is a lethal disease,” says Anton Porsteinsson, the William and Sheila Konar Endowed Professor of Psychiatry and director of the University’s Alzheimer’s Disease Care, Research, and Education Program.

A new study shows that the brain’s waste removal system serves as both trash collector and delivery service, providing neurons with a protein important to maintaining cognitive function while simultaneously cleaning brain tissue. The research may help explain why different genetic varieties of the protein, called apolipoprotein E (apoE), can indicate risk for Alzheimer’s disease or promote longevity.

The study was led by Rashid Deane, B.Sc., Ph.D., a research professor in the University of Rochester Medical Center Department of Neurosurgery and member of the Center for Translational Neuromedicine, and appears in the journal Molecular Neurodegeneration.

ApoE is responsible for delivering cholesterol to nerve cells in the brain and plays a key role in synaptic plasticity, the process by which neurons build new connections in order to learn and store memories.

Caring for a loved one with dementia can be very
stressful, but two URMC research studies are
exploring ways to help caregivers manage stress
and improve their own health.

Caring for a loved one with Alzheimer’s disease or dementia can not only be very stressful, but can negatively affect the well-being of the caregiver. A pair of studies at the University of Rochester Medical Center is exploring ways to help caregivers manage stress and improve their own health so they can more effectively provide care for their loved one.

Kathi Heffner, Ph.D., associate professor in the School of Nursing and Department of Psychiatry, and Jan Moynihan, Ph.D., the George L. Engel Professor in Psychosocial Medicine in the Departments of Psychiatry and Microbiology and Immunology, were awarded more than $5.66 million in NIH funding for two five-year randomized clinical intervention trials focusing on reducing the effects of caregiving on immune health.

Heffner is principal investigator on a cognitive training intervention trial looking at different types of brain training activities and whether they have an effect on the aging of the caregiver’s immune system. Moynihan is leading a study on mindfulness-based stress reduction (MBSR), to see if mindfulness can lead to better immune response to the influenza vaccine.

The grant application to support the Rochester Society for Neuroscience chapter was recently funded due to efforts by Past President, Doug Portman. Thanks to Doug's efforts and excellent leadership over the last two years, we can continue our efforts to increase neuroscience awareness and education in our community.

The current Chapter President, Liz Romanski, would like to congratulate the organizers and volunteers for hosting a very successful, first ever, Rochester Brain Bee on February 11, 2017 (picture attached). Ten students from high schools in the Rochester area competed in the Brain Bee, answering questions spanning a large body of neuroscience facts covering brain development, cognition, disease processes, neuroimaging, etc. The three finalists in the Brain Bee were:

1. Neli Kotlyar, Pittsford Mendon High School (grade 10)
2. Maha Khokhar, Pittsford Sutherland High School (grade 12)
3. Kathryn Gentile, Pittsford Mendon High School (grade 11)

Heather Natola and Nicole Peltier were the organizers of the Brain Bee, and were assisted by volunteers from the Brain Awareness committee including Neuroscience graduate students Jessie Hogestyn and Josh Hinkle, and BCS grad students Alyssa Kersey, Carol Jew, and Matt Overlan. The winner of the Brain Bee will fly to Baltimore, MD in March for the National Brain Bee. Funding was made possible by the Society for Neuroscience Chapter, the Neuroscience Graduate Program, and the Department of Neuroscience with prizes from local businesses and donations from Drs. Huxlin and Nehrke. Great job all!

Nina Schor, M.D., Ph.D., William H. Eilinger Chair of Pediatrics and the pediatrician-in-chief at UR Medicine’s Golisano Children’s Hospital, has been named the recipient of the Child Neurology Society’s 2017 Hower Award, the organization’s highest honor.

The award is given annually to a child neurologist for being an outstanding teacher, scholar, and for making high levels of contributions to the field and to the Child Neurology Society. Schor, who has spent much of her career researching neuroblastoma, one of the most common childhood cancers, will be recognized at the society’s annual meeting in October, in Kansas City, Mo. She will also have the honor of giving the annual Hower lecture.

“I am so honored and excited to accept this award and present the associated lecture to an audience comprised of my colleagues, friends, mentors, and trainees,” said Schor.

The Child Neurology Society is the preeminent non-profit professional association of pediatric neurologists in the United States, Canada, and worldwide. Schor, the University of Rochester Medical Center’s seventh Chair of the Department of Pediatrics, joined the university in 2006.

Feng Vankee Lin, assistant professor of Nursing, and Rajeev Raizada, assistant professor of Brain and Cognitive Sciences, have been awarded a Collaborative Pilot Award in Health Analytics from the Goergen Institute for Data Science.

The one-year project will use big data in an effort to develop an algorithm for predicting Alzheimer’s disease. The project will analyze large brain-imaging datasets and use multiple machine-learning approaches to uncover diagnostic patterns and create a more reliable predictive model for detecting Alzheimer’s disease.

“It will help initiate a new research area focusing on neuroimaging methodology development in relation to Alzheimer’s disease,” said Lin.

The award includes a $35,000 grant for the project, which runs from Feb. 1, 2017 to Jan. 31, 2018.

Located in Wegmans Hall, the Goergen Institute for Data Science is a hub for interdisciplinary data science research. Its work in health analytics – using data to predict individual health outcomes – includes advances in using data to help analyze the brain more effectively and sharing the data with other researchers to discover more ways to improve outcomes for patients.

Major Step toward Longer-Lasting HIV Treatment

A drug developed at the University of Rochester Medical Center extends the effectiveness of multiple HIV therapies by unleashing a cell’s own protective machinery on the virus. The finding, published today in the Journal of Clinical Investigation, is an important step toward the creation of long-acting HIV drugs that could be administered once or twice per year, in contrast to current HIV treatments that must be taken daily.

The drug, called URMC-099, was developed in the laboratory of UR scientist Harris A. (“Handy”) Gelbard, M.D., Ph.D. When combined with “nanoformulated” versions of two commonly used anti-HIV drugs (also called antiretroviral drugs), URMC-099 lifts the brakes on a process called autophagy.

Normally, autophagy allows cells to get rid of intracellular “trash,” including invading viruses. In HIV infection, the virus prevents cells from turning on autophagy; one of the many tricks it uses to survive. When the brake on autophagy is lifted, cells are able to digest any virus that remains after treatment with antiretroviral therapy, leaving cells free of virus for extended periods of time.

Harris A. (“Handy”) Gelbard, M.D., Ph.D.

“This study shows that URMC-099 has the potential to reduce the frequency of HIV therapy, which would eliminate the burden of daily treatment, greatly increase compliance and help people better manage the disease,” said Gelbard, professor and director of UR’s Center for Neural Development and Disease, who has studied HIV/AIDS for the past 25 years. The finding builds on previous research that Gelbard conducted with Howard E. Gendelman, M.D., professor and chair of the Department of Pharmacology/Experimental Neuroscience at the University of Nebraska Medical Center.

Liz Romanski, Associate Professor of Neuroscience at the University of Rochester, will serve as President of the Rochester Chapter of the Society for Neuroscience for the 2017-2108 term.

The Chapter is involved in a number of activities designed to strengthen Neuroscience research, education, and outreach in the Rochester area. In addition to Dr. Romanski, the Chapter's current leadership council includes Secretary/Treasurer Chris Holt, Faculty Councilor Amy Kiernan, Past Presidents Krystel Huxlin and Doug Portman, Postdoctoral Councilor Sarah Heilbronner, Graduate Student Councilor Heather Natola, and Administrative Coordinator Ania Dworzanski.

Congratulations Liz!!

A study led by Jessica Cantlon, associate professor of brain and cognitive sciences, suggests that primates have the ability to distinguish large and small quantities of objects, irrespective of the surface area they appear to occupy.

Adults and children in the US, adults from a 'low numeracy' tribe in Bolivia and rhesus monkeys ALL possessed the ability to distinguish between large and small quantities of objects, regardless of the surface area they occupy. This ability is likely a shared evolutionary trait, according to a study. The nonverbal visual tests could be used in assessing early math education in young children.

Elevated levels of the brain protein tau following a sport-related concussion are associated with a longer recovery period and delayed return to play for athletes, according to a study published in the January 6, 2017 issue of Neurology®, the medical journal of the American Academy of Neurology. The findings suggest that tau, which can be measured in the blood, may serve as a marker to help physicians determine an athlete’s readiness to return to the game.

Despite the 3.8 million sports-related concussions that occur annually in the United States, there are no objective tools to confirm when an athlete is ready to resume play. Returning to play too early, before the brain has healed, increases an athlete’s risk of long-term physical and cognitive problems, especially if he or she sustains another concussion. Currently, physicians and trainers must make return-to-play decisions based on an athlete’s subjective, self-reported symptoms and their performance on standardized tests of memory and attention.

A team led by Jessica Gill, R.N., Ph.D. of the National Institute of Nursing Research at the National Institutes of Health and Jeffrey Bazarian, M.D., M.P.H. of the University of Rochester Medical Center evaluated changes in tau in 46 Division I and III college athletes who experienced a concussion. Tau, which plays a role in the development of chronic traumatic encephalopathy or CTE, frontotemporal dementia and Alzheimer’s disease was measured in preseason blood samples and again within 6 hours following concussion using an ultra-sensitive technology that allows researchers to detect single protein molecules.

David Williams, Ph.D.

Researchers at the University of Rochester Medical Center have developed a new imaging technique that could revolutionize how eye health and disease are assessed. The group is first to be able to make out individual cells at the back of the eye that are implicated in vision loss in diseases like glaucoma. They hope their new technique could prevent vision loss via earlier diagnosis and treatment for these diseases.

In a study highlighted in the Proceedings of the National Academy of Sciences, Ethan A. Rossi, Ph.D., assistant professor of Ophthalmology at the University of Pittsburgh School of Medicine, describes a new method to non-invasively image the human retina, a layer of cells at the back of the eye that are essential for vision. The group, led by David Williams, Ph.D., Dean for Research in Arts, Sciences, and Engineering and the William G. Allyn Chair for Medical Optics at the University of Rochester, was able to distinguish individual retinal ganglion cells (RGCs), which bear most of the responsibility of relaying visual information to the brain.

A new study sheds light on changes in the brain that may explain why young infants who are placed in an orphanage or foster care often struggle with social relationships later in life.

The findings, which were published in the journal Developmental Psychobiology, come from a team of researchers led by Julie Fudge, M.D., with the University of Rochester Medical Center (URMC) Department of Neuroscience. The scientists revisited data from a study involving monkeys that took place more than a decade ago at the University of Pittsburgh and was designed to observe the behaviors of newborns that were separated from their biological mothers and raised by another group of females. The original study noted that these monkeys differed in their social interactions -- such as grooming, huddling together, and normal aggression -- compared to those that were raised by their mothers.

Like humans, monkey's brains are not fully developed at birth and the animals are dependent upon the nurturing of caregivers for many months early in life. Fudge and her colleagues wanted to see if there could find an association between the absence of a primary caregiver and biological changes in the brain that could explain the lasting social impairment observed in the monkeys.