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April 27, 2017

Research Notes

Motor cortical neurons adjust to control tasks

New Pitt research done in collaboration with Carnegie Mellon University’s College of Engineering reveals that motor cortical neurons optimally adjust how they encode movements in a task-specific manner. The findings enhance our understanding of how the brain controls movement and have the potential to improve the performance and reliability of brain-machine interfaces, or neural prosthetics, that assist paralyzed patients and amputees.

The study explored the change in brain activity during simple motor tasks performed through virtual reality in both 2-D and 3-D. The researchers wanted to know if the motor cortical neurons would automatically adjust their sensitivity to direction when presented with a wide range of possible directions instead of a narrow one. Previous research in the field has suggested that this phenomenon, called dynamic range adaptation, is known to occur in neurons sensitive to sound, touch and light, prompting the researchers to ask if the same phenomena would apply to neurons in the motor system that are associated with movement.

Said Robert Rasmussen, School of Medicine student and first author of the study: “When you walk out into the bright summer sun, you squint, and the neurons in your retina use dynamic range adaptation to automatically increase their sensitivity so that you can clearly see until the clouds pass over again. This feature allows the brain to better encode information by using its limited resources efficiently. We wanted to find out if our brain encodes movement in the same way.”

The results revealed that dynamic range adaptation did indeed occur in the motor cortical neurons. Based on these findings, the researchers concluded that this feature is widespread throughout the brain.

Explained Andrew Schwartz, neurobiology faculty member, chair in systems neuroscience at the School of Medicine and a member of the University of Pittsburgh Brain Institute: “We found that dynamic range adaptation isn’t restricted to sensory areas of the brain. Instead, it is a ubiquitous encoding feature of the cortex. Our findings show that it is a feature of information processing that your brain uses to efficiently process whatever information it is given — whether that is light, sound, touch or movement. This is an exciting result that will motivate further research into motor learning and future clinical applications.”

The study was published in eLife.

Funding was provided by the National Science Foundation, the Pennsylvania Department of Health Research, the National Institutes of Health (NIH) and the Defense Advanced Research Project Agency.

Shaken baby detection improved

Researchers at Children’s Hospital and the School of Medicine have developed and refined a blood test that could help clinicians identify infants who may have had bleeding of the brain as a result of abusive head trauma, sometimes referred to as shaken baby syndrome. The science behind the test is described in JAMA Pediatrics.

The serum-based test, which needs to be validated in a larger population and receive regulatory approval before being used in clinical practice, would be used to detect acute intracranial hemorrhage, or bleeding of the brain. Infants who test positive then would have further evaluation via brain imaging to determine the source of the bleeding.

Said senior author Rachel Berger, pediatrics faculty member in the school and chief of the Child Advocacy Center at in the hospital: “Abusive head trauma (AHT) is the leading cause of death from traumatic brain injury in infants and the leading cause of death from physical abuse in the United States.”

However, approximately 30 percent of AHT diagnoses are missed when caretakers provide inaccurate histories or when infants have nonspecific symptoms such as vomiting or fussiness. Missed diagnoses can be catastrophic as AHT can lead to permanent brain damage and even death.

Berger and colleagues at Children’s Hospital and the Safar Center for Resuscitation Research in the school have long been researching approaches to detect acute intracranial hemorrhage in infants at risk.

In the current study, the researchers collaborated with Axela, a Canadian molecular diagnostics company, to develop a sensitive test that could reduce the chances of a missed diagnosis by using a combination of three biomarkers along with a measure of the patient’s level of hemoglobin, the protein that carries oxygen in blood. Axela’s automated testing system allowed the researchers to measure multiple biomarkers simultaneously using an extremely small amount of blood, an important characteristic of a test designed to be used in infants.

To arrive at the formula, called the biomarkers for infant brain injury score (BIBIS), for discriminating between infants with and without intracranial hemorrhage, the team used previously stored serum samples from a databank established at the Safar center.

The team then evaluated the predictive capacity of the BIBIS value in a second population of 599 infants who were enrolled prospectively at three study sites in the United States. In addition to Children’s Hospital, infants were enrolled at Ann and Robert H. Lurie Children’s Hospital in Chicago and Primary Children’s Hospital in Salt Lake City. The test correctly detected acute intracranial hemorrhage because of abusive head trauma approximately 90 percent of the time, a much higher rate than the sensitivity of clinical judgment, which is approximately 70 percent.

“The test is not intended to replace clinical judgment, which is crucial,” said Berger. “Rather, we believe that it can supplement clinical evaluation and in cases where symptoms may be unclear, help physicians make a decision about whether an infant needs brain imaging.”

The specificity of the test — or the ability to correctly identify an infant without bleeding of the brain who would not require further evaluation — was 48 percent. The researchers aimed for the test to be highly sensitive rather than maximizing accuracy, since missing a diagnosis has more serious consequences than performing brain imaging in babies without the condition.

The research team has filed a joint U.S. patent for the test.

Additional Pitt authors included Janet Fromkin, Richard Saladino and Patrick M. Kochanek.

Colleagues from Axela, the University of Utah and Lurie Children’s Hospital also contributed to the research.

The study was funded by NIH.

Wheelchair runs on compressed air

PneuChairA new waterproof motorized wheelchair that runs entirely on compressed air — designed, developed and constructed at the Human Engineering Research Laboratories (HERL) — was unveiled at Morgan’s Wonderland, a theme park in San Antonio, Texas. The park was built specifically for individuals with disabilities, and 10 of these chairs will be available to patrons at the venue’s new splash park, Morgan’s Inspiration Island.

The patent-pending PneuChair uses high-pressured air as an energy source instead of heavy batteries and electronics. The chair weighs about 80 pounds overall and takes just 10 minutes to recharge, compared to eight hours to charge an electric mobility device.

HERL, which is a joint effort of Pitt, the U.S. Department of Veterans Affairs and UPMC, already was working on a prototype of the PneuChair when it heard from representatives of Sports Outdoor and Recreation (SOAR), a nonprofit organization established by The Gordon Hartman Family Foundation of San Antonio to oversee Morgan’s Wonderland. They asked HERL for help in developing powered mobility for the new splash park.

Said Rory Cooper, HERL director and faculty member in the Department of Rehabilitation Science and Technology: “Their needs and our research were essentially an ideal match. The potential to open opportunities for people with disabilities who need powered mobility to access splash parks, water parks, beaches or pools is transformative.”

Said Brandon Daveler, a graduate student researcher and the lead mechanical design engineer on the project: “The PneuChair uses a simpler design without a lot of electronics and software. If something goes wrong, any of the components can be purchased at your local hardware store.”

The maximum distance on one fully charged tank is around three miles, about a third of the distance an electric chair can travel before it needs to be recharged. Pitt and SOAR are looking to establish a long-term licensing agreement wherein the PneuChair could be used in a variety of markets — personal care homes, shopping venues, grocery stores or airports.

Watchful eye needed on immunization rates

Recent federal recommendations against offering the inhaled nasal influenza vaccine due to lack of effectiveness could lead to more flu illness in the U.S. if the inhaled vaccine becomes effective again or if not having the choice of the needle-less vaccine substantially reduces immunization rates, according to an analysis led by  School of Medicine scientists.

The findings, published online and scheduled for an upcoming issue of the American Journal of Preventive Medicine, indicate that close surveillance will be needed to ensure that the U.S. Centers for Disease Control and Prevention (CDC) recommendation against the nasal vaccine — called the live attenuated influenza vaccine, or LAIV — continues to do more good than harm.

“The CDC is being appropriately cautious and doing the right thing based on available data,” said lead author Kenneth J. Smith, faculty member in medicine and clinical and translational science. “However, our study finds that it would take only relatively small changes to tip the scales back in favor of offering the LAIV, so close monitoring is very important.”

The Pittsburgh vaccination research group (PittVax) is one of a few sites across the U.S. that track flu in patients who received and did not receive the annual flu vaccine. The data they collect is shared with the CDC’s advisory committee on immunization practices and led to the CDC’s recommendation against LAIV last year after data from the two previous flu seasons showed it to be ineffective at preventing influenza A, which is typically the most common strain. In the past, the LAIV was a common vaccine offered to children 2-8 years old.

Under current conditions, only offering the needle-delivered flu vaccine results in 20.9 percent of children ages 2-8 getting the flu, compared with 23.5 percent if both the needle and nasal vaccine are offered.

However, if the LAIV effectiveness improves and can prevent flu in more than 63 percent of the people who get it, then it once again becomes beneficial to offer both forms of vaccination.

“Interestingly, there has been no decrease in LAIV effectiveness in other countries, and we’re still unsure why this is,” said Smith.

The researchers also found that if not having the needle-less vaccine as an option drives down vaccination rates by 18.7 percent or more, then offering both options is the better recommendation.

“PittVax will continue collecting, analyzing and reporting on flu cases and flu vaccine effectiveness in the Pittsburgh region, helping guide flu immunization recommendations,” said senior author Richard K. Zimmerman, faculty member in the Department of Family Medicine and the Graduate School of Public Health’s Department of Behavioral and Community Health Sciences. “This kind of surveillance is critical to charting the best course to save lives from influenza, which kills thousands annually.”

Other authors on this study were Mary Patricia Nowalk, Angela Wateska and Jonathan M. Raviotta of Pitt; Shawn T. Brown and Jay V. DePasse of the Pittsburgh Supercomputing Center, and a researcher from Soongsil University in Seoul, Republic of Korea.

This project was funded by National Institute of General Medical Sciences.

—Compiled by Marty Levine


The University Times Research Notes column reports on funding awarded to Pitt researchers as well as findings arising from University research.

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