Study examines kids’ early rehab of acute brain injury

With the support of a $1.9 million grant from the Patient-Centered Outcomes Research Institute (PCORI), Ericka Fink, faculty member in pediatric critical care medicine at the School of Medicine, will examine early rehabilitation protocols (ERP) for children with acute brain injury (ABI).

The randomized, controlled trial will, for the first time, evaluate an early rehabilitation protocol versus usual care to improve outcomes for children admitted to the pediatric intensive care unit at Children’s Hospital with ABI.

The grant will fund a multicenter needs assessment to further characterize the current practices, barriers to care and resources for physical, occupational, speech and behavioral assessment and therapies needed for early rehabilitation protocol implementation in pediatric intensive care units. It is one of 33 proposals PCORI approved for funding to advance patient-centered comparative effectiveness research and to help patients, health care providers and other clinical decision-makers make better-informed choices.

ERP addresses the functional, cognitive and emotional needs of the critically ill child. It is delivered by a multidisciplinary team with the aim of optimizing outcomes important to the patient and family.

Fink will lead the multidisciplinary research project with a critical care physician at Ann & Robert H. Lurie Children’s Hospital of Chicago. Other collaborators include experts in pediatric brain injury, rehabilitation, psychiatry and outcomes.

Said Fink: “We developed the early rehabilitation protocol program to include interventions that will optimize outcomes most important to patients and families including emotional, cognitive and functional ability and quality of life. Should ERP be shown to be effective, we will provide assistance to other parties interested in implementing it in their institutions.”

All PCORI-funded projects were selected through a competitive review process in which scientists, patients, caregivers and other stakeholders helped evaluate more than 325 applications for funding. Proposals were evaluated on scientific merit, how well they will engage patients and other stakeholders and their methodological rigor, among other criteria.

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Learning pathways research could help stroke recovery

Learning a new skill is easier when it is related to an ability that we already possess. For example, a trained pianist might learn a new melody more easily than learning how to hit a tennis serve.

Neural engineers from the Center for the Neural Basis of Cognition (CNBC) — a joint program of Pitt and Carnegie Mellon University — have discovered a fundamental constraint in the brain that may explain why this happens. Published as the cover story in Nature, the study found for the first time that there are constraints on how adaptable the brain is during learning and that these constraints are the key determinant for whether a new skill will be easy or difficult to learn. Understanding the ways in which the brain’s activity can be “flexed” during learning eventually could be used to develop better treatments for stroke and other brain injuries.

Lead author Patrick T. Sadtler, a PhD candidate in the Department of Bioengineering, compared the study’s findings to cooking: “Suppose you have flour, sugar, baking soda, eggs, salt and milk. You can combine them to make different items — bread, pancakes, and cookies — but it would be difficult to make hamburger patties with the existing ingredients. We found that the brain works in a similar way during learning. We found that subjects were able to more readily recombine familiar activity patterns in new ways relative to creating entirely novel patterns.”

For the study, the research team trained animals to use a brain-computer interface, similar to ones that have shown recent promise in clinical trials for assisting tetraplegics and amputees.

The researchers recorded neural activity in the motor cortex and directed the recordings into a computer, which translated the activity into movement of a cursor on the computer screen. This technique allowed the team to specify the activity patterns that would move the cursor. The subjects’ goal was to move the cursor to targets on the screen, which required them to generate the patterns of neural activity that the experimenters had requested. If the subjects could move the cursor well, that meant that they had learned to generate the neural activity pattern that the researchers had specified.

The researchers found that their subjects learned to generate some neural activity patterns more easily than others, since they only sometimes achieved accurate cursor movements. The harder-to-learn patterns were different from any of the pre-existing patterns, whereas the easier-to-learn patterns were combinations of pre-existing brain patterns. Because the existing brain patterns likely reflect how the neurons are interconnected, the results suggest that the connectivity among neurons shapes learning.

Said Aaron P. Batista, bioengineering faculty member and co-principal investigator on the study: “We wanted to study how the brain changes its activity when you learn and also how its activity cannot change. Cognitive flexibility has a limit, and we wanted to find out what that limit looks like in terms of neurons.”

The research team included Pitt faculty members Kristin Quick and Elizabeth Tyler-Kabara and faculty from Carnegie Mellon, Stanford and the Palo Alto Medical Foundation.

The study was funded by the National Institutes of Health (NIH), the National Science Foundation (NSF) and the Burroughs Wellcome Fund.

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Can synthetic material self-organize?

The Charles E. Kaufman Foundation, part of The Pittsburgh Foundation, awarded $1.95 million in grants to support cutting-edge scientific research at institutions across Pennsylvania. Anna Balazs, Distinguished Robert v. d. Luft Professor of Chemical and Petroleum Engineering, and a Penn State researcher received a grant for the study, “Autonomous Interacting Microbotic Systems.”

The goal of the proposed research is to answer the challenge: Can we design self-powered synthetic materials that self-organize — based on signals from each other and from their environment — and thereby perform complex, coordinated tasks?

The specific questions to be addressed are:

• Can we design purely synthetic materials that autonomously process energy and information and, hence, begin to mimic salient biological behavior?

• Can these materials effectively “network” to share information and perform cooperative, coordinated activities?

The research will focus on devising chemically powered “motors” and “pumps.” Motors are motile objects that transduce chemical energy into mechanical motion. When these motors are anchored onto a surface, they transfer their chemically generated force to the surrounding fluid and, hence, function as fluidic pumps. By creating systems of autonomous motors and pumps that have the capacity to transduce energy, move and communicate, researchers will lay the foundations for fabricating self-powered, small-scale robotic systems that can perform “collaborative” work.

The proposed research involves a new collaboration that uses knowledge of synthetic chemistry and catalysis, as well as fluid dynamics and computational modeling.

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Permanent magnets improve power generation

A more energy-efficient and less time-consuming method to produce permanent magnets for power generation in machines from electric cars to windmills is the potential of an NSF grant to researchers at the Swanson School of Engineering and Alcoa Technical Center in New Kensington.

The proposal, “Manufacturing of Nanostructure-Enhanced Mn-Al-based Materials via Modulated Machining and Thermomechanical Consolidation for High-Performance Magnets” was awarded a $299,998 Grant Opportunity for Academic Liaison with Industry award that runs through April 30, 2017.

The study is being led by the Swanson school’s Jörg M.K. Wiezorek, a mechanical engineering and materials science faculty member; co-PIs include M. Ravi Shankar, faculty member and Whiteford Faculty Fellow of industrial engineering.

The interdisciplinary academia-industry team will use a novel machining-based process combined with low-temperature consolidation to generate dense bulk ferromagnetic aggregates, or permanent magnets, for high-performance applications.

The grant also will support graduate student fellowships in the lab.

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Brain’s anti-relapse circuit could help addictions

Yaoying Ma, research associate in the lab of Yan Dong, neuroscience faculty member in the Dietrich School of Arts and Sciences, notes that biology, by nature, has a yin and a yang, a push and a pull.

Addiction, particularly relapse, she finds, is no exception.

She was the lead author of a paper published online in Neuron that posits that it may be possible to ramp up an intrinsic anti-addiction response as a means to fight cocaine relapse and keep the wolves of relapse at bay.

This paper is the first to establish the existence of brain circuitry that resists a relapse of cocaine use through a naturally occurring neural remodeling with “silent synapses.”

The work is a follow-up on a recent study conducted by Dong and his colleagues, which was published in Nature Neuroscience in November. The team used rat models to examine the effects of cocaine self-administration and withdrawal on nerve cells in the nucleus accumbens, a small region in the brain that is associated with reward, emotion, motivation and addiction. Specifically, they investigated the roles of synapses, the structures at the ends of nerve cells that relay signals.

The team reported in its earlier study that when a rat uses cocaine, some immature synapses are generated, which are called “silent synapses” because they are semifunctional and send few signals under normal physiological conditions. After that rat stops using cocaine, these silent synapses mature and acquire their full function to send signals. They then will send craving signals for cocaine if the rat is exposed to cues previously associated with the drug.

The current Neuron paper shows that there’s another side of silent synapse remodeling. Silent synapses that are generated in a specific cortical projection to the nucleus accumbens by cocaine exposure become “unsilenced” after cocaine withdrawal, resulting in a profound remodeling of this cortical projection. Additional experiments show that silent synapse-based remodeling of this cortical projection decreases cocaine craving. Importantly, this anti-relapse circuitry remodeling is induced by cocaine exposure itself, suggesting that the body has its own way to fight addiction.

Dong, the paper’s senior author, said that the pro-relapse response is predominant after cocaine exposure. But since the anti-relapse response exists inside the brain, it possibly could be tweaked clinically to achieve therapeutic benefits.

Ma noted that this finding “may provide insight into ways to manipulate this yin-yang balance and hopefully provide new neurobiological targets for interventions designed to decrease relapse. Our ongoing study is exploring some unusual but simple ways to beef up the endogenous anti-relapse mechanism.”

Others contributing to the study from Pitt were Susan Sesack, Yanhua Huang, Xiusong Wang, Changyong Guo, Yan Lan and Judith Balcita-Pedicino.

Also contributing were researchers from the Allen Institute for Brain Science in Seattle, Northeastern Normal University in China, Rosalind Franklin University of Medicine and Science in Illinois, NIH and the European Neuroscience Institute in Germany.

—Compiled by Marty Levine

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