Newswise PHILADELPHIA Picture a future where embedded medical devices not only treat and teach patients, but learn from them. Imagine chronic pain being managed without the negative side effects of opioids. Penn Medicine researchers are working to make those scenarios a reality. These initiatives are among innovative new National Institutes of Health (NIH) funded efforts that are mapping the future of medicine.

The NIH has selected two researchers from the Perelman School of Medicine at the University of Pennsylvania to receive its prestigious Directors Awards, part of the NIH Common Funds High-Risk, High-Reward Research Program honoring exceptionally creative scientists. Brian Litt, MD, a professor of Neurology, Neurosurgery, and Bioengineering, was honored with a Pioneer Award for $5.6 million, supporting novel neurodevice research. Gregory Corder, PhD, an assistant professor of Psychiatry and Neuroscience, was selected as a New Innovator Award winner, receiving $2.4 million for research investigating the mechanisms of chronic pain.

This NIH initiative, designed to fuel research endeavors that are more opened-ended and have a potentially broader effect on scientific understanding compared to more traditional research, awards these to scientists to support research over a five-year period. The 2020 Penn recipients are among 85 awardees nationally:

Pioneer Award Ghost in the Machine: Melding Brain, Computer and Behavior

The Pioneer Award challenges investigators to pursue new research directions and develop groundbreaking, high-impact approaches to a broad area of biomedical or behavioral science. This award supports Litts work to develop a new generation of autonomous neurodevicesimplanted machines that can question, record, and combine learning algorithms based on neurological signals and feedback to act and alter human behavior on the fly.

In epilepsy, for example, these devices would predict and prevent seizures; in Parkinsons patients, implants will measure and communicate with patients to improve mobility, reduce tremor and enhance responsiveness. Other implants might improve hearing or psychiatric symptoms by querying patient perceptions, feelings, and altering stimulation patterns algorithmically to improve them. The loop is closed in real time, so the host can change their behavior based upon device feedback to improve their health.

Imagine this: A 30 year-old veteran walks into a bar. None of the patrons are aware of the anti-seizure device in his brain, or the traumatic brain injury that requires it. After he drinks a beer, his phone vibrates with a text from the implantable device asking what hes doing and sharing his probability of a seizure has increased. And with a quick explanation from the veteran, the device stimulates and suggests avoiding a second beverage, Litt explains. Were working towards this future, with the help of the Pioneer Award.

This is a paradigm shift from todays simple devices, which rely on physicians to give device feedback to patients and change simple parameters by hand during occasional office visits. Litts goal is to build a foundation for responsive implants that can collaborate with hosts, linking human experience and perception to machine algorithms, actions, and therapy, predicting and preventing events before they start. Not only will the patient teach the device, but the device will teach the patient.

Grant ID: DP1 NS122038-01.

New Innovator Award Harnessing Cortical Neuromodulation to Disrupt Pain Perception

The New Innovator Award supports unusually innovative research from early career investigators who have not yet received a research project grant or equivalent NIH grant. The award will support Corders efforts to research the mechanisms of chronic paina major health crisis in the United States, affecting millions, and a driver of the opioid epidemic.

Corders goal is to identify which parts of the brain are important for pain perception and which circuits impact pain relief from opioids. He hopes to decode how this neural activity evolves during chronic pain. Once the brain circuits and pathways that contribute to the suffering and perception of pain are identified, they can be targeted for potential therapeutics which could be more effective at reducing pain and without the addictive elements of prescription opioids.

Corder envisions these next generation pain therapeutics leveraging viral-delivered cell-specific gene therapies to disrupt the pain-processing circuits in the cortex. This would will allow patients to sense pain but without the unpleasant aversion.

We currently have a limited understanding of the neural pathways in the brain that contribute to pain, which has been a significant barrier for treating pain efficiently, without negative side effects. But, if we can identify and understand these circuits, we can then try to rewrite the neural code of pain, Corder said. Picture being able to specifically target the one desired brain region or circuit that processes pain in order to provide pain relief. This research will help us lay the groundwork for new classes of therapeutics, which could have a profound and broad impact for treating patients with chronic pain, while reducing the burden of the national opioid crisis.

Grant ID: DP2 GM140923-01.

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Penn Medicineis one of the worlds leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of theRaymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nations first medical school) and theUniversity of Pennsylvania Health System, which together form a $8.6 billion enterprise.

The Perelman School of Medicine has been ranked among the top medical schools in the United States for more than 20 years, according toU.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $494 million awarded in the 2019 fiscal year.

The University of Pennsylvania Health Systems patient care facilities include: the Hospital of the University of Pennsylvania and Penn Presbyterian Medical Centerwhich are recognized as one of the nations top Honor Roll hospitals byU.S. News & World ReportChester County Hospital; Lancaster General Health; Penn Medicine Princeton Health; and Pennsylvania Hospital, the nations first hospital, founded in 1751. Additional facilities and enterprises include Good Shepherd Penn Partners, Penn Medicine at Home, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health, among others.

Penn Medicine is powered by a talented and dedicated workforce of more than 43,900 people. The organization also has alliances with top community health systems across both Southeastern Pennsylvania and Southern New Jersey, creating more options for patients no matter where they live.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2019, Penn Medicine provided more than $583 million to benefit our community.

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Penn Medicine Researchers Receive Prestigious National Institutes of Health Directors Awards - Newswise