"Imagine spending your entire life snorkeling, and then suddenly you go scuba diving," Batista said. "You'll quickly realize you were only scratching the surface of a deeper reality."

For Batista, a neural engineer with decades of research exploring brain-computer interfaces at the University of Pittsburgh’s Swanson School of Engineering, that realization stemmed from his earliest visits to Dr. Jorge González-Martínez's operating room, which became the foundation for a novel postdoctoral training program: Neural Engineering in Neurosurgery: Bridging Engineering to Clinical Practice. 

“Engineers tend to think about the brain by thinking about computational circuitry that underlies behavior, while surgeons are thinking about how they can treat individuals who are suffering today,” Batista said. “And despite the fact that our engineering laboratories sit just an eight-minute walk from the neurosurgery operating rooms, it’s a distance that we’ve rarely covered, until now.”

Supported by a new National Institutes of Health (NIH) T32 award (1T32NS147937-01), the program will connect postdoctoral fellows from the Swanson School of Engineering's Department of Bioengineering, residents from the School of Medicine's Department of Neurological Surgery, and 32 affiliated faculty members and clinicians to work on research projects that improve neurosurgical practice. 

“This program is a perfect example of how Pitt's strengths across professional disciplines promotes the creation of interprofessional teams.” said Paul Wallach, vice chancellor for health sciences education and executive vice dean for academic affairs at the School of Medicine. “These teams then serve as drivers of innovation in clinical care."

Teaming Up to Improve Neurosurgical Practice

Co-directed by Batista, professor of bioengineering at the Swanson School, and Jorge González-Martínez, professor and vice-chair of neurological surgery at the School of Medicine, the program will bring together eight trainees, including four postdoctoral associates and four residents, who will work side by side on team-based research projects.

“Postdocs will shadow neurosurgeons in the operating room, and residents will pursue a deep dive into laboratory research under the direct supervision of their engineering mentor,” Batista said. “That way, our trainees will get to work on a project that actually matters for doctors.”

Designed to close the gap separating neurosurgery and bioengineering, each pair will be matched to one of eight collaboration clusters built around surgical areas where bioengineering and clinical strengths already overlap: epilepsy, stroke, speech and language mapping, sensory restoration, pain, trauma, movement disorders, and brain tumors.

“I’m excited about partnering with engineers to build a better understanding of the mechanisms related to epilepsy," González-Martínez said. “And, we can use this program to better understand how the signals we see in our micro-electrode recordings interact with behavior, not only for epilepsy, but also for language and movement disorders."

Several ongoing collaborations at the University provided the groundwork for the type of research that the program hopes to accelerate. Among them, work by González-Martínez and School of Medicine collaborator Elvira Pirondini uses stimulation in the thalamus, a central coordinator for the brain’s cerebral cortex, to help restore speech and motor function in patients recovering from stroke.

Other projects include helping surgeons better decide how much tissue is safe to remove during tumor resection, developing new spinal cord stimulation approaches for chronic pain, and building next-generation implantable sensors and closed-loop neuromodulation systems for movement and emotional disorders.

"As doctors, we typically stay in the OR, so we don't have many chances to interact with engineers," González-Martínez said. "We know the challenges and the gaps we need to work on, but we don't always know how to answer those challenges.”

Trainees will also complete a yearlong course, BIOENG 2805: Translational Neural Engineering, to explore the current landscape of neural engineering and identify paths for innovation. Both Batista and González-Martínez hope the program will end up doing far more than just train individual researchers — they see it as a first step toward building a lasting, formal bridge between engineering and medicine at the University.

"This is a very unique opportunity to finally create an educational environment that combines neural engineering and neurosurgery," González-Martínez said. "We’ve never had something like this, and it’s just the first step to creating a larger integration between bioengineering and neurosurgery.”

Dopamine is a chemical messenger that regulates the brain’s circuits responsible for planning and executing controlled movement. Current treatments include deep-brain stimulation (DBS) via implanted electrodes to jam faulty signals caused by the neurodegeneration, often in conjunction with dopamine-promoting medication.

Helen Schwerdt, assistant professor of bioengineering, hypothesizes that using a separate brain probe to measure dopamine as a biomarker at a high resolution can help establish the optimum parameters for the use of DBS and medication, reduce side effects, and produce better clinical outcomes.

She and her second-year doctoral student, Ritesh Shrivastav, are the recipients of the 2026 Hunter Family Foundation Innovation in Neuroscience Program award, which supports translational research in neuroscience at the University of Pittsburgh. Schwerdt and Shrivastav collaborate with Jorge González-Martínez, vice chair of the Department of Neurological Surgery, on the clinical applications of the technology.

“The field lacks knowledge of what abnormal dopamine signals look like in Parkinson’s that are potentially causing the motor issues in people suffering this disease,” Schwerdt said. “We’re trying to address this by creating a tool that can provide a readout of the dysregulated neurochemical environment to potentially personalize the treatment.”

Shrivastav, who has been working in Schwerdt’s lab since he was an undergraduate, said he learned of the Hunter program by attending the Community of Innovators meetings held weekly by the Office of Innovation and Entrepreneurship during both the fall and spring semesters.

“These high-risk/high-reward studies are difficult to get funded, but are exactly how device feasibility must be proven for clinical translation,” he said. “My interest is in translating these tools for research and commercial use. The Hunter funding is critical for validating clinical use cases for our probe.”

The award funds will be used to conduct animal and human studies in which their dopamine sensor can be incorporated into neurosurgical procedures performed by González-Martínez.

“Deep brain stimulation has been around for decades now, but nobody knows for sure how it works,” Shrivastav said. “These studies will help us determine dopamine’s value as a biomarker for the first time and how it can be measured to improve clinical outcomes. If we are successful, we can move onto regulatory testing and potentially pursue the approvals necessary to get this to market and improve patients’ lives.”

“Dr. Schwerdt and her team are tackling one of the most persistent unknowns in Parkinson’s care: what’s actually happening at the neurochemical level during deep brain stimulation. If their dopamine biomarker proves successful, it could transform DBS from a broadly effective but imprecise tool into a truly personalized therapy — one that’s calibrated to each patient’s unique neurochemistry,” said Evan Facher, vice chancellor for innovation and entrepreneurship and associate dean for commercial translation at the Pitt School of Medicine. “That kind of impact, translating fundamental bioengineering research into real clinical benefit for people living with Parkinson’s, is precisely what the Hunter Family Foundation Innovation in Neuroscience Program was created to accelerate.”

The Hunter Program is made possible by the generous support of the Hunter Family Foundation. Learn more.

This article was originally published by the Office of Innovation and Entrepreneurship (7/28/26). Reposted with permission.

“None,” his colleague said. “That's just a piece of tissue I put under the microscope.”

"My jaw dropped," said Vande Geest, professor of bioengineering at the University of Pittsburgh’s Swanson School of Engineering. “The ability to image collagen in 3D without fixing it first means I can look at it under mechanical load, and I can also watch it grow and change. As a soft tissue biomechanist, there is really no better thing."

Two-photon microscopy is just one of the many impactful imaging modalities that are put to work across Pitt’s campus. Bioengineering researchers like Vande Geest have built the tools and expertise to ask and answer questions that couldn't have been posed before, from the tiniest cellular movements to the complex architecture of the aging human brain.

Two-Photon Microscopy

Two-photon microscopy fires pulses of infrared light into tissue. Unlike conventional light, infrared travels deep without scattering, but it only produces fluorescence at the precise focal point where the beam converges. At Pitt’s Center for Biotechnology and Bioengineering, you willl find a few of these microscopes, each customized for a different scientific purpose. One of these devices is helping Takashi (TK) Kozai, Ernest E. Roth professor of bioengineering, peer into the brain to analyze a largely unexplored corner of neuroscience. 

"Brain tissue is like a very foggy, hazy environment, and neurons aren't on the surface level, so we have to image a little deeper to actually see them," said Kozai. “That’s where two-photon comes into play and can help us see very specific areas of the brain.”

Kozai’s team studies what happens when devices like electrodes are implanted, not just to neurons, but to the surrounding community of glial cells. Because glial cells don't generate electrical signals that electrodes can detect, they are effectively invisible to conventional methods. 

"But with 2P, you can label different subtypes of neurons or other cell-types so that you can see which ones are activated under which type of stimulus," Kozai said. "You can decode beyond what an electrode can decode."

Kozai’s microscope is available for researchers of all disciplines to use, which helps him better understand how to improve the long-term performance of implanted devices toward the ultimate goal of restoring motor function in people with spinal cord injuries or treating vision loss in patients who are blind. Vande Geest, on the other hand, uses his scope for different terrain entirely: studying the extracellular matrix of soft tissues found in the eye, blood vessels, peripheral nerves, and more. Collagen, the structural protein that gives these tissues their mechanical character, produces a signal under two-photon illumination that makes it visible without any dye or label. More importantly, it stays visible while the tissue is alive, under load, and changing over time.

"I study how tissues are built and how they change, and this is the system that lets me do it. I can image it, deform it, and image it again," he said. “I can literally watch collagen remodel.”

Vande Geest has also reconfigured his microscope to function as a 3D printer that can fabricate structures at the scale of individual cells. The same instrument that shows the architecture of a tissue sample can now print scaffolds that replicate it, opening a path toward implantable tissues that could treat vascular and ocular disease.

“A majority of the intellectual property (IP) I've developed involves benchtop platforms for mimicking human disease in 3D tissue culture," Vande Geest said. "We can take human stem cells, differentiate them, and assemble them into something that might actually tell a clinician whether a patient should be treated more aggressively for something like glaucoma, and that specialized platform gives you information that clinical measurement alone just can't."

A Picture’s Worth 

For Lance Davidson, William Kepler Whiteford Professor of bioengineering, collecting an image is only the beginning. Using traditional confocal microscopy, which uses focused laser light to build three-dimensional images one optical slice at a time, his lab studies how cells rearrange inside tissues under mechanical stress, using frog embryos as a model system. These embryos are optically transparent and mechanically tractable in ways that make them ideal for stretching, compressing, and perturbing living tissue while imaging what happens inside it.

"We use a lot of microscopy to collect images, and it's all light microscopy, not anything too complex." Davidson said. "But we combine these tools with molecular genetic approaches, so we can install a fluorescent protein within a cell or tissue that indicates where forces are generated, or how material properties adapt to the environment.”

After collecting time-lapse sequences of cells moving through a tissue, Davidson’s team builds custom image processing pipelines that segment individual cells, track which cells are neighbors at each time point, and quantify how frequently and in what direction those relationships change. In a recent study, that analysis revealed something novel in the raw footage: a pair of counter-rotating flows inside a developing tissue, moving in opposite directions.

 "Once we processed it, we could see these really incredible flows.” Davidson said. “They looked like tropical cyclones or vortices on the surface of the sun, and so we turned to quantify the strength of those rotations using tools borrowed from astrophysics."

For Davidson, however, the most important work happens after the microscope turns off. A striking image is still just a picture until it's been broken down, processed, and reduced to something a statistician can work with.

"The adage ‘a picture is worth a thousand words’ is actually quite terrible for science," Davidson said. “Numbers are like currency, and we use images to get that currency, so you really want each picture to be worth a single number."

Sound as Sight

Of all the imaging modalities in use, ultrasound may be the easiest to underestimate. It's one of the oldest, the most affordable, the most common, and it doesn't carry the glamour of a two-photon beam. But across the university, researchers are finding new uses for it that go far beyond the routine. 

Kozai's lab, for instance, recently found that low-intensity ultrasound can reduce the glial scarring that builds up around implanted brain electrodes, keeping signals clearer over time and opening new possibilities for modulating non-neuronal brain cells. In addition, Kang Kim, professor of bioengineering and medicine at UPMC’s Heart and Vascular Institute, is also pushing ultrasound far beyond its typical uses.

"Ultrasound has been out there for decades," Kim said. "It's safe, non-invasive, and real-time. But because of how well we understand physics, we can now start to combine it with other modalities and push it in directions people didn't think were possible."

One of Kim’s current projects involves a catheter-based imaging system designed to peer inside blood vessels at the microscopic level. The project addresses plaque vulnerability, assessing which arterial plaques are likely to rupture and send a clot toward the heart or brain. One signature of a dangerous plaque is the presence of tiny microvessels growing within it, and to detect them, Kim's team developed an intravascular probe and signal processing approach that can image those structures at scales previously considered beyond the physical limits of the modality.

"We claim this is one of the first kinds of intravascular super-resolution imaging of microvessels," Kim said. "There are emerging fields even beyond imaging where ultrasound can be used. It is not just a tool for looking; it is becoming a tool for doing."

MRI and the Whole-Brain Picture

While microscopes allow for cellular or tissue analysis and ultrasound can peer inside vessels and soft tissue in real time, there's a hard physical limit to how deep light can travel. When researchers need to see the structure, connectivity, and metabolic activity of the entire brain, they turn to MRI. 

Bistra Iordanova uses a combination of optical imaging techniques in her work, but uses structural and functional MRI (fMRI) in tandem with optical approaches to get a window into brain-wide activity that no light-based  system can match.

"With optics, we can get the cell resolution, but MRI covers the entire brain at once, which makes it indispensable for questions about large-scale connectivity and system-wide disease," said Iordanova, assistant professor of bioengineering. “Structural MRI shows the size and shape of brain regions and how they change with age, while fMRI tracks blood flow oxygenation as a proxy for neural activity in real time.”

Using these techniques, she's currently working on a methodologically unusual project: directly comparing data between mice and humans to help design multiscale models of how brain metabolism can change the risk for dementia. This approach spans three scales: two-photon microscopy to quantify blood cell velocity, neural activity, and metabolite levels at the cellular level; wide-field imaging to capture how mitochondrial activity moves across cortical networks; and whole-brain MRI to explore how energy metabolism shapes functional connectivity across both animal models and human cohorts.

"To make these comparisons work, we transform the imaging data to the same parameters," Iordanova said. "In the human brain, a vessel might be two centimeters long, but in a mouse brain, it’s two millimeters. And a mouse only lives two years while a human lives 80. This kind of cross-species translation can actually be quite difficult, but it's where the real clinical relevance lies.” 

Building the Brain Scan

While many researchers like Iordanova are using the existing MRI scanners in their work, Tamer Ibrahim, professor of bioengineering, has spent more than 20 years engineering the technology itself. 

For MRI, the stronger the magnetic field, the greater the signal-to-noise ratio, and the finer the structural detail that becomes visible. But scanners at a high magnetic field like 7 Tesla come with a serious engineering problem: the interactions between high-frequency electromagnetic waves and human tissue can create dead zones in the image, or regions of the brain that simply produce no signal. 

Ibrahim's lab, the 7 Tesla Bioengineering Research Program (7TBRP), has solved this problem with a custom radiofrequency coil system called Tic-Tac-Toe, and its second-generation successor, the Tac G2, introduced in 2022. The Tac G2 is, by Ibrahim's account, the only system in the world that has comprehensively eliminated the signal void problem, allowing researchers to run any type of MRI study at 7T without imaging barriers.

"There are significant challenges when scanning at 7T," Ibrahim said. "But our anti-claustrophobia Tac G2 coil system is, to my knowledge, the only one in the world that has successfully and comprehensively solved this problem.” 

The practical consequences are substantial. A study published in Human Brain Mapping from Ibrahim's team, comparing 3T and 7T performance across 350 healthy adults, found that 7T produces stronger correlations with age-related brain changes across every measure examined such as cortical volume, subcortical volume, white matter, cortical thickness. More importantly, it found a study that would require 350 participants at 3T could achieve the same statistical significance with approximately 100 participants at 7T.

That efficiency gain means that studies that were previously too expensive, too slow, or too logistically demanding to conduct become feasible. Since the Tac G2's introduction, it has been used in more than 2,500 human scans, already surpassing its predecessor's total in less than half the time. More than 40 NIH-funded studies across aging, psychiatry, neurology, and neuroscience are currently running on the system.

"When our coils are used in human studies, it's incredibly rewarding, far more rewarding than just publishing a paper," he said. "We're developing devices that clinicians and scientists use, and the result isn't just pretty pictures. We're not making something that just could be used some time in the future, we’re impacting human life now."

The Full Picture

These researchers work with different tools, different tissues, and different diseases, yet the opportunity for collaboration between modalities seems to increase by the day. A shared conviction ties all of their work together: there is no perfect imaging modality. Every technique involves tradeoffs between resolution and depth, speed and sensitivity, invasiveness and detail. For Iordanova, those limitations are precisely what makes the field so interesting and allows for such innovation. 

"If you don't have solid image analysis, it doesn't matter if you have a fancy machine," she said. "That's the beauty of bioengineering - you get to reach into any pocket you want. Optics, electrical engineering, image processing, artificial intelligence. The biology department says stick to cells, the electrical engineering department says just do the signal processing, but bioengineering lets you have it all."

Interested in using a 2P microscope for your research project? Contact TK Kozai for more information at tdk18@pitt.edu. 

“The GRFP is a highly competitive award, and we are extremely proud of our winners and honorable mentions this year,” said Michele V. Manuel, U. S. Steel Dean of Engineering at Pitt. “This funding will provide critical financial support for these students to expand their research that benefits all of us.”

The NSF also recognized two members of the Swanson School community with honorable mentions: Jack Hall, a graduate student in Civil and Environmental Engineering, and Sead Nikšić (BS ECE ’23). Four alumni, Dalia Fantini (BS BIOE '23), Kelly Larson (BS IE ‘18), Frederick Laudati (BS ECE '25), and Paul Walter (BE MEMS ’20) also received fellowships this year. 

This year’s Swanson School awardees are:

Casey Cargill

Cargill is a first-year PhD student in the Department of Bioengineering, where she specializes in the Tissue Engineering and Regenerative Medicine (TERM) track. Advised by Jonathan Vande Geest in the Soft Tissue Biomechanics Laboratory, Cargill’s research focuses on addressing vision loss caused by conditions such as age-related macular degeneration.

Cargill collaborates with vision scientists and clinicians to develop patient-specific, 3D bioengineered models of the eye’s vascular system. By replicating the complex blood vessel networks and fluid dynamics within the eye, her work seeks to better understand how vascular disruptions contribute to blindness and to support the development of more personalized therapeutic strategies. Cargill is also a member of the Graduate Women in Engineering Network, the Black Graduate Student Alliance, and the Graduate Biomedical Engineering Society (BMES) chapter. 

“My Jamaican heritage instilled in me, ‘Labor for learning before you grow old; for learning is better than silver or gold. Silver and gold will vanish away, but a good education will never decay.’ Cargill said. This fellowship supports my research as well as my personal values, allowing me to keep investing in academic growth and using it to benefit others.”

Sophia Freemyer

Freemyer is a senior undergraduate student in the department of Civil and Environmental Engineering pursuing a minor in geology and a certificate in public communication of science and technology through the Frederick Honors College. Freemyer began research in Sarah Haig’s INHALE Lab, followed by a summer internship at Oak Ridge National Laboratory through the Department of Energy’s Science Undergraduate Laboratory Internship program, where she worked on a materials science crystallization project. Freemyer later served as an ORISE Fellow at the National Energy Technology Laboratory (NETL). 

“My research interests are centered around critical mineral extraction from unconventional sources, specifically waste streams such as acid mine drainage, coal refuse, and produced water from oil production.” Freemyer said. “This area of research not only strengthens our domestic supply of these important materials but also utilizes streams that would end up as pollution in our environment.”

Freemyer is also an active member of the Pitt Band, where she served as a squad leader during her sophomore and junior years and as piccolo section leader her senior year. She also held leadership roles within the Varsity Marching Band Council and Kappa Kappa Psi, the national honorary band fraternity, and is a member of the Society of Women Engineers and Tau Beta Pi engineering honor society. After graduation, Freemyer’s NSF fellowship will fund her PhD studies at Columbia University's Earth and Environmental Engineering Department in the lab of Ngai Yin Yip. 

“I am beyond excited to win this award.” Freemyer said. “Having my application accepted is extremely validating for my future goals of becoming a researcher, with expert reviewers agreeing that I have enough promise as a future scientist to fund my graduate studies.”

Aragya Goyal

Goyal is a senior undergraduate student in the Department of Electrical and Computer Engineering, focusing on autonomous systems. His research centers on field robotics, with a particular interest in underwater and space exploration technologies. Since his freshman year, Goyal has collaborated with researchers at Carnegie Mellon University under the guidance of Howie Choset and David Wettergreen, contributing to projects such as the underwater snake robot “HUMRS” and the “Zoë 2” rover, which investigates passive steering mechanisms for planetary exploration. Looking ahead, he is interested in advancing multi-robot collaboration in complex field environments, including coordinated swarms of autonomous underwater vehicles.

Goyal has also been actively involved in the Robotics and Automation Society, where he has developed both technical and professional skills while contributing to a strong engineering community. Goyal applied for the NSF GRFP with the goal of strengthening his research proposal on multi-robot coordination, initially viewing the process as a learning opportunity. With guidance from mentor Geordan Gutow and strong recommendations from his research advisors, however, he successfully refined his application and was awarded the fellowship. This award removes a significant financial barrier to pursuing graduate studies, enabling him to focus fully on advancing robotics research.

“I feel extremely excited and grateful to have been granted this opportunity. My parents and I moved to the United States in 2013 and became citizens in 2021. It was likely one of the best opportunities for my family and had allowed me to apply for this fellowship and receive it.” Goyal said. “Not only that, but my decision to come to Pitt has been equally valuable, and I am glad I made that decision as it provided me with a hub and network of highly technical people who are always ready to help and teach you. The Pitt ECE faculty is excellent, and my peers are brilliant, and it is because of the community surrounding me that I was able to win this award.”

Ritesh Shrivastav

Shrivastav is a first-year PhD student in the Department of Bioengineering, on the neural engineering track under the mentorship of Helen Schwerdt. In the Schwerdt lab, his work centers on developing minimally invasive tools to measure dopamine in the human brain with high spatial and temporal resolution.

Shrivastav's research aims to elucidate how pathological dopamine fluctuations in the brain manifest as motor dysfunction in Parkinson’s patients. According to Shrivastav, this is essential foundational science for the future development of adaptive treatment technologies that could be personalized to each patient’s unique brain state. 

“Post-graduation, I would love to continue to build upon my research by developing treatments for Parkinson’s disease such as using dopamine as a biomarker for adaptive deep brain stimulation." Shrivastav said. "In the long term, I hope to translate this work into a startup focused on bringing these technologies from the lab to the clinic. This fellowship would provide critical support for the validation research that I will conduct during my PhD, laying a foundation for future commercialization and real-world impact.”

Vanshika Singh

Vanshika Singh is a first-year PhD student in the Department of Bioengineering pursuing the neural engineering track. They conduct their research in the B.I.O.N.I.C. Lab under the mentorship of Takashi (TK) Kozai. 

Singh’s research explores how non-neuronal cells in the brain, specifically microglia, contribute to inflammation and metabolic stress across neurological disease states. Their recent work has focused on how microglial calcium dynamics change in response to electrode-induced injury, and I’m interested in extending this work to explore how these signaling changes manifest in the context of Alzheimer’s disease. Singh is also interested in investigating ultrasound as a neuromodulatory tool, particularly its mechanistic targets and how it may influence microglial activity and calcium signaling.

Beyond the lab, Singh is actively engaged in mentorship and scholarly service, spending the past two summers mentoring high school students through the Hillman Academy and recently as a reviewer for Ingenium, an undergraduate research journal at the Swanson School of Engineering. Singh also presented their research on microglial responses to electrode insertion injury at the Society for Neuroscience Conference 2025.

“It is an incredible honor to be an NSF GRFP Fellow.” Singh said. “The three years of support will give me the freedom to pursue curiosity-driven research and take intellectual risks that might otherwise be difficult. Beyond funding, this fellowship marks a meaningful milestone in my path toward a career in academic research."

George M. and Eva M. Bevier Professors

Aaron Batista

New appointment | Sept 1, 2025 – Aug 31, 2030

Batista’s research focuses on how the brain learns and controls movement. His laboratory discoveries help to improve brain-computer interfaces, systems that establish a direct communication pathway between the brain's electrical activity and external devices, allowing users to translate neural signals into commands to operate computers, robotic limbs, or  software. He’s also part of the Simons Collaboration on Ecological Neuroscience (SCENE) from the Simons Foundation, which unites leading scientists across neuroscience and machine learning to discover how the brain performs sensorimotor interactions. 

Xinyan Tracy Cui

Reappointment | Sept 1, 2025 – Aug 31, 2030

Cui's lab develops smart biomaterials and neural interface technologies designed for implantation in neural tissue to enable diagnosis and treatments. Her research spans flexible multimodal neural probes for interrogation of the nervous system; neural modulation therapies; biomimetic implant designs and coatings that promote seamless tissue integration; as well as on-demand drug delivery systems and biosensors. Cui holds nine patents, is widely cited  with more than 16,000 citations, and is a co-founder of a Pitt-based startup, Vanish Therapeutics, translating research from the lab to real world impact. 

Ernest E. Roth Professor

Takashi (T.K.) Kozai

New appointment | Sept 1, 2025 – Aug 31, 2030

Kozai's B.I.O.N.I.C. Lab examines the neurocomputational roles of glial and mural cells in healthy and diseased brain, and the biophysics of electrical and ultrasonic neural recording and stimulation at the tissue-electrode interface. His laboratory employs chronic in vivo two-photon microscopy, functionally evoked electrophysiology, electrochemical impedance spectroscopy, cyclic voltammetry, post-mortem immunohistochemistry, and transgenic and AAV-based biological intervention strategies. 

“I feel honored and energized by the responsibility that comes with a named professorship. The title acknowledges the collective work of my trainees and collaborators, who consistently push the boundaries of what we can measure, model, and engineer in the nervous system.” Kozai said. “It also reflects the Swanson School's commitment to research where clinical challenges drive new scientific questions and laboratory discoveries reshape therapeutic strategies.”

Leighton E. Orr and Mary N. Orr Faculty Fellow

Gelsy Torres-Oviedo

New appointment | Sept 1, 2025 – Aug 31, 2029

At the Sensorimotor Learning Lab, Torres-Oviedo’s group studies neuromechanical mechanisms for locomotor learning in humans with and without neurological disorders by investigating the human ability to adapt walking patterns and learn new movements through interactions with the world. The team combines psychophysical experiments and computational tools to investigate locomotor learning in unimpaired subjects and patients with cortical lesions. 

Layla Banihashemi, associate professor of psychiatry and bioengineering at Pitt's School of Medicine and Swanson School of Engineering, has been named the 2026 recipient of the Paul D. MacLean Award from the Society for Biopsychosocial Science and Medicine. This honor recognizes outstanding neuroscience research in psychosomatic medicine, particularly work that advances understanding of how emotion, brain function, and physical health are interconnected.

Banihashemi researches the neural mechanisms linking the brain and body, with a focus on how these systems shape stress reactivity and contribute to affective psychopathology. Her work examines how early-life experiences, particularly childhood adversity, influence central visceral circuits, key pathways that regulate stress responses and play a critical role in mental and physical health.

“I am incredibly honored to receive the MacLean Award from SBSM." Banihashemi said. "I feel deeply grateful to everyone who has made this work possible - to mentors and collaborators who so generously give of their time and expertise, to lab members who dedicate tremendous effort to these studies, and to SBSM for this distinction and providing me with a scientific home."

Banihashemi delivered the MacLean Award Lecture, a plenary talk titled “The ‘Visceral Brain’: Linking Childhood Adversity to Mind-Body Health” at the Society for Biopsychosocial Science and Medicine’s Annual Scientific Meeting in March. The MacLean Award was named after Paul D. MacLean, a visionary physician who emphasized the importance of the brain–body basis of emotion and its relevance for health and behavior. Banihashemi’s research advances this work through translational approaches that bridge preclinical neuroanatomy with human neuroimaging, and she's among a distinguished group of past recipients such as Antonio Damasio, Lisa Feldman Barrett, Helen Mayberg, and Richard Davidson. 

Research on spinal cord stimulation led by scientists and physicians at the University of Pittsburgh School of Medicine was spotlighted as one of the most significant projects supported by the National Institute of Neurological Disorders and Stroke (NINDS) over its 75‑year history.

NINDS, a core institute within the National Institutes of Health, has driven many of the field’s most groundbreaking advances since 1950. To mark its 75th anniversary, the institute is highlighting landmark work that’s shaped modern neuroscience.

“NINDS‑supported neuroscience has evolved the field as we know it,” said Marco Capogrosso, assistant professor of neurological surgery, School of Medicine. “Being recognized as part of this milestone underscores Pitt’s leadership at the forefront of translational neuroscience.”

Spinal cord stimulation (SCS) is emerging as a powerful way to restore movement by reactivating weakened or dysfunctional neural circuits. Capogrosso and colleagues first showed that because spinal pathways often remain structurally intact after stroke, targeted SCS can boost residual signals and restore arm and hand movement. In early human trials, stimulation rapidly improved strength, precision and range of motion, with some gains lasting even after the device was removed. Surgeons, including Peter Gerszten, Peter E. Sheptak Professor of Neurological Surgery, School of Medicine, helped refine the minimally invasive implantation techniques that make this possible.

The same research team has now extended SCS to neurodegenerative disease. In a Nature Medicine study published in February 2025, Capogrosso, alongside first author Genís Prat-Ortega, assistant professor of neurological surgery, and corresponding author Elvira Pirondini, assistant professor of physical medicine and rehabilitation, both School of Medicine, demonstrated that stimulating sensory spinal nerves can “reawaken” silent motor neurons in adults with spinal muscular atrophy. Over a month of targeted sessions, all participants showed improved motoneuron function, reduced fatigue and better walking ability—far exceeding gains from exercise or medication alone.

Together, these findings point to a unifying principle: precisely timed spinal stimulation can restore function in circuits weakened by stroke, injury or degeneration. Ongoing trials aim to determine how durable these improvements are and how SCS can be combined with rehabilitation or pharmacologic therapies to maximize recovery.

You can read the article here. 

Hecheng Jin, PhD candidate in the 7T Bioengineering Research Program (7TBRP), received the first-place poster award at the International Society of Magnetic Resonance in Medicine (ISMRM) Annual Meeting this spring for her presentation “Design and implementation of a 1H/31P dual-tuned head coil at 7T.”

Jin works with Tamer Ibrahim, professor of bioengineering at the Swanson School of Engineering, to design hardware for 7 Tesla MRI systems — an advanced imaging technique that operates at a much higher magnetic field than conventional clinical MRI. 

The increased magnetic field strength of 7 Tesla MRI allows for more detailed images of the brain, helping researchers detect subtle changes that might go unnoticed with standard imaging. With higher-strength MRI, however, researchers are not only interested in the brain’s structure but are also looking to understand the brain’s metabolism — which can lead to patient discomfort during the imaging process. 

“We need two types of images to see the structure and metabolic activity of the brain, so we have to use two separate setups and scan patients twice, which can take up to an extra hour just for preparation.” Jin said. “Many of our studies involve people with Alzheimer’s disease or Lewy body dementia, so this process is especially uncomfortable for them.”

At ISMRM, Jin showcased her design and implementation of a novel integrated MRI head coil capable of performing both high-resolution structural imaging and chemical phosphorus spectroscopy, which would improve patient comfort and scan efficiency by eliminating the need to reposition patients mid-exam. Jin said she was honored to receive the award, and noted that the collaborative effort of her lab helped her end up with the first place spot. 

“Our goal is to fully develop an integrated coil that works for both imaging types so we can improve image quality and patient experience.” Jin said. “I think this is one of the most supportive environments I’ve ever been in. My advisor always gives me unique guidance and encouragement, and my lab mates are incredibly supportive, so I’m grateful for everyone's support in helping me succeed.” 

Takashi Kozai, associate professor of bioengineering and Ernest E. Roth faculty fellow at the Swanson School of Engineering, in collaboration with Michigan State University’s Wen Li, received a 5-year, $3.4M R01 grant from the National Institutes of Health (NIH) to develop advanced brain stimulation technology using lab-grown diamonds.

Kozai’s project, “Mechanisms of localized neuronal excitation with diamond Wireless Axon and electrical microstimulation,” aims to engineer both hardware and stimulation software for better understanding and treating neurological conditions by developing diamond "Wireless Axon" electrodes for use in intracortical microstimulation.

“One of our aims is to look at how electrical brain stimulation impacts different groups of neurons.” Kozai said. “When we electrically stimulate sensation in the brain, we want to know more about how the neuron groups act when we activate them. If we electrically stimulate someone’s brain and they feel pressure or cooling or warming sensations, we're trying to investigate what different groups of neurons are being activated.”

Conventional electrical brain stimulation typically activates a sparse and distributed population of neurons. To improve neuronal targeting, the team will be using photovoltaics — or light-driven stimulation — which lets them stimulate neurons with voltage rather than with electrical current. This approach allows them to activate a more specific population of neurons by selectively activating the neuron’s cell body instead of its surrounding axons. 

“We've been working with a couple of folks who make diamond electrodes with various impurities and dopants, which allows us to drive their activity at different efficacies.” Kozai said. “Because the devices we’re building are wireless, they’re not moving every time someone has a heartbeat or brain movement. This gives us a new level of control and helps avoid common issues with electrodes like glial scarring in the brain.” 

The diamonds are doped with the chemical element boron—a process that involves intentionally adding impurities to a material to modify its electrical conductivity—allowing the team to enhance the conductivity of the diamonds and generate voltages more efficiently. Kozai’s team will study how different amounts of boron impact the electrode’s function, and ultimately hope that these more efficient electrodes will provide deeper insights into the inner workings of the brain. 

“A few groups around the world have been doing intracortical stimulation to restore sensation, but it’s amazing that despite using these tools, we still don’t fully understand what they’re actually doing to populations of neurons in the brain.” Kozai said. "Once we understand that, we can begin adapting it into therapies, treatments, and even cures for neurodegenerative conditions, sensory loss, and paralysis."

 Ting, a postdoctoral fellow who completed her PhD in bioengineering at Pitt, will receive $100,000 to support her research on whether deep brain stimulation in the motor thalamus can improve speech and swallowing in patients with a traumatic brain injury. She plans to test implants in three or four patients for up to one month, giving them stimulation to see if their swallowing improves.  

 “Especially for those with more moderate to severe impairments, they typically just have to live with these issues, or get feeding tubes, or modify their diets, and have somebody watch them eat to make sure they don't choke,” Ting said. “This research hopefully can help prevent choking and make a significant difference in the patients’ quality of life and health.” 
 
Her mentors include Elvira Pirondini, assistant professor of physical medicine and rehabilitation, and Jorge González-Martínez, director of the Department of Neurological Surgery Epilepsy and Movement Disorders Program, both School of Medicine. 
 
That team, with Ting as the entrepreneurial lead, was among the 2023 winners of the Pitt Innovation Challenge in the Clinical and Translational Science Institute for the application of the technology in stroke. Ting also went through the Life X Accelerator program to build out the commercialization plan for this therapeutic intervention. She is now participating in Equalize Startups, an entrepreneurship program for women, and is working to launch a startup.  

“We are thrilled to support Jordyn’s research to help improve the lives of patients struggling with speech and swallowing disorders,” said Sue Hunter, a member of the Hunter family. “Her work aligns beautifully with our mission of supporting projects that advance innovations toward commercialization.” 

The Hunter TBI Translational Research grant is administered by the Office of Innovation and Entrepreneurship (OIE). OIE provides opportunities for innovators designed to support and accelerate innovation, including funding programs, intellectual property protection guidance, patenting support, startup consulting and more. Learn more at innovation.pitt.edu. 

Release originally composed by University of Pittsburgh School of Medicine on 05/08/25. 

To answer this question, the newly launched Simons Collaboration on Ecological Neuroscience (SCENE) from the Simons Foundation will unite leading scientists across neuroscience and machine learning to discover how the brain performs sensorimotor interactions. Among the six interdisciplinary teams selected for this 10-year, $80 million initiative are Xaq Pitkow, associate professor at Carnegie Mellon University’s Neuroscience Institute, and Aaron Batista, professor of bioengineering at the University of Pittsburgh Swanson School of Engineering. 

SCENE builds on principles from ecological psychology, which posit that one of the brain’s core functions is to encode affordances. An affordance is an opportunity for action available in an environment — for example, a chair affords the opportunity to sit, and a perch affords the opportunity for a bat to land. By encoding affordances, the brain closely links perception with action in an efficient manner. Identifying how the brain encodes and uses this information will bridge gaps in our understanding of the neural basis of cognition.

“This project aims to bring in modern neuroscience and computational methods to move beyond the laboratory for understanding perception and action in natural environments,” Batista said. His team will focus on recording neural signals in the motor cortex while non-human primate subjects perform cognitively demanding tasks that demand precision and skill. 

By combining Batista’s findings with additional recorded data from other brain regions involved in perception, like the visual system and prefrontal cortex, the team will develop a whole-brain dataset. A team of theorists and data scientists, including Pitkow, will use artificial systems and machine learning to study this dataset and mathematically describe how the brain represents affordances and prompts action. 

“Our team is using a mathematical framework known as the Partially Observable Markov Decision Process (POMDP) to investigate what the brain cares about when making these decisions, how it encodes useful information to select an action or behavior, and how the way that brains make choices relate to each other across tasks, brain areas, and even species,” Pitkow said.  

The multi-institutional collaboration will officially begin July 1 and provide over $8M per year across the six teams of researchers. Simons Neuroscience Collaborations are designed to span 10 years, enabling scientists to conduct large-scale longitudinal studies that typically aren’t feasible under conventional grants.

“This is an exciting opportunity because the time scale of this grant allows for extensive progress not usually possible,” Pitkow said. “The team we have is really fun to work with, and with such a rich depth of expertise we can cover a wide range of things like brain computer interface, augmented reality experiments, and even work with animals in their natural landscapes, including bats navigating island ecosystems, to learn and compare their brain representations to ours.”

The Simons Foundation is committed to supporting research in neuroscience, and particularly in actualizing the potential in bringing together teams with wide expertise in pursuit of shared objectives. SCENE follows on their successful funding model, adding to their ongoing neuroscience programs including the Simons Collaboration on the Global Brain and the Simons Collaboration on Plasticity and the Aging Brain. Like those previous endeavors, SCENE will bring together groups of outstanding scientists to address fundamental questions about brain function, focusing on fields in which new developments can create novel opportunities for exploration that reverberate through the broader field of neuroscience.

“We received hundreds of intriguing proposals and are truly excited by the many outstanding scientific directions put forward by our community,” said Alyssa Picchini Schaffer, vice president and senior scientist of the Simons Collaborations in Neuroscience. “It was a rigorous evaluation process, and we are confident that SCENE will push the entire field forward by reshaping our understanding of cognition and behavior.”

At the Swanson School of Engineering Department of Bioengineering, more than 30 primary and secondary faculty members collaborate on interdisciplinary research and mentor students in the department’s graduate programs in neural engineering. Their work spans five core areas of research:

• Neural stimulation and modulation
• Neural imaging and computation
• Neurodegenerative diseases and neurological rehabilitation 
• Neural interface development 
• Neuroethics, training, policy, and global health

Brain Computer Interface

One of the most impactful areas of neural engineering research at Pitt is brain-computer interface (BCI) technology—a system that detects brain activity and translates it into real-time outputs. Pioneered by Andrew Schwartz, distinguished professor of neurobiology, BCI technology has laid the foundation for modern neural prosthetics. Using BCI, Schwartz and his team decoded signals from the motor cortex in primates to enable actions like reaching and grasping, demonstrating that primates could use their brain activity to control robotic arms with remarkable precision. 

BCI technology at Pitt has since led to groundbreaking clinical breakthroughs, including a 2012 study where Jan Scheuermann controlled a robotic limb using only her thoughts—one of the first demonstrations of this kind in humans—and a clinical trial where Nathan Copeland has been able to experience the sensation of touch through a robotic arm. Researchers like Aaron Batista, professor of bioengineering who recently leveraged BCI technology to understand the sequences of neural populations, or Jennifer Collinger, professor of physical medicine and rehabilitation who uses BCIs to restore movement for people with spinal cord injury and amputation at the Rehab Neural Engineering Labs (RNEL), continue to utilize BCI technology in their research to better understand the behavior of the brain itself and to directly benefit patients.

“I am deeply committed to a clinical trial that is developing an intracortical brain-computer interface,” Collinger said. “The BCI is implanted into the motor and somatosensory cortex, and we are working with people who have tetraplegia to try to understand how the brain controls movement, how it is impacted by sensory feedback, and how we can restore sensory feedback that's been lost. Ultimately, our goal is to develop BCIs that restore upper limb function and increase independence and participation after injury.”

Neural Stimulation & Neural Interface Development

While BCIs offer a powerful way to decode brain signals, complementary approaches like neural stimulation are also expanding what’s possible in sensory restoration. Researchers like Takashi Kozai, associate professor of bioengineering, are advancing techniques such as intracortical microstimulation (ICMS) to restore sensory experiences, offering new possibilities for patients with brain injuries, neurodegenerative diseases, and other sensory impairments. ICMS stimulates specific regions of the brain responsible for sensory processing, but the challenge of neurostimulation goes beyond simply activating neural circuits. 

"ICMS works by activating both neuronal and non-neuronal cells, but understanding how these responses change over time is critical," Kozai said. “One challenge we face is perceptual fading, where the system’s effectiveness diminishes. Our goal is to understand the factors that contribute to this fading and design systems that maintain long-term, reliable function.”

Addressing these challenges requires not only advances in stimulation techniques, but also innovations in the physical interfaces between technology and the brain. Xinyan (Tracy) Cui, professor of bioengineering and a leader in neural interface development, designs biocompatible materials and coatings that improve the longevity and function of brain-machine interfaces. 

“As neural engineers, we are tool developers,” Cui said. “We develop the tools for neuroscientists and clinicians to study a wide variety of diseases, and we design the implantable devices that clinicians are using to directly help patients.”  

Cui and other neural engineers in her field develop implantable devices that record neural signals, stimulate the nervous system, sense neural transmitters, and deliver therapeutics. They also work to optimize how the brain interacts with these devices using novel techniques such as ultrasound to reduce scarring inside the brain when devices are implanted. 

Sharper Imaging, Deeper Understanding 

Neural engineering researchers at Pitt also have the ability to see detailed images of the brain and its activity through the work of Tamer Ibrahim, professor of bioengineering who develops ultrahigh field human imaging techniques using the 7 Tesla magnetic resonance imager (7T MRI). Consistently optimized by Ibrahim’s graduate students through “Tic-Tac-Toe” radiofrequency coil technology, the 7T MRI imager is frequently used for projects in bioengineering, psychiatry, neurology, and pathology, and helps researchers understand how a variety of conditions like aging, dementia, sickle cell disease, and depression appear in the brain. The 7 Tesla is the most complex MRIs in use, with extremely high resolution capabilities.

“Interventional studies on depression and Alzheimer’s disease can assess how neuroimaging biomarkers correlate with the medications that patients are taking, and help us determine whether they're improving on the medication or not,” Ibrahim said. “Getting homogeneous excitation in the human brain at 7 Tesla is quite difficult from a physics point of view, but the 2nd Generation Anti-claustrophobia Tic Tac Toe coil system developed by the 7 Tesla Bioengineering Research Program (7TBRP) gives us and our collaborators the ability to visualize the brain structures and connectivity with minimal artifacts.”

Clinical Collaborations Enhancing Patient Outcomes

Clinical translation of neural engineering technology directly impacts clinicians like Jorge González-Martínez, vice-chair of the department of neurological surgery and board-certified neurosurgeon, who studies brain electrophysiology, cognition, and language in patients undergoing epilepsy and movement disorder surgery. He also operates on many of these patients, providing direct treatment using Stereo-electroencephalography (SEEG), a minimally invasive procedure that uses electrodes placed directly into the brain to identify the source of epileptic seizures. 

"In order to advance medicine, especially in my field of epilepsy and functional neurosurgery, we need to collaborate with bioengineers,” González-Martínez said. “Progress simply won’t happen if we don’t join forces. Neural engineering is fundamental—it allows me to use signal processing to better understand where seizures originate in the brain, enabling safer and more effective surgeries. Bioengineers help us develop new methods, instruments, and treatment approaches, from device design to signal interpretation, and I will continue to rely on these collaborations because they are essential to advancing the field and improving patient care." 

Whether it’s for improving methods in neurosurgery with clinicians like González-Martínez, collaborating with industry partners and the FDA for translational technology development, or using basic science approaches to better understand chronic pain and psychiatric conditions, tackling the complex challenges of neural engineering requires a multidisciplinary approach. For Collinger, collaboration across the university is the driving force that allows researchers at Pitt to take these challenges head-on. 

“Neural engineering requires an understanding of biology, neuroscience, and medicine, and one person can't really be an expert in all of those things,” Collinger said. “But here, I think collaboration with each other is just part of our culture, and people are looking to work with other laboratories and try to make collaborations as seamless as possible, which I think is a major strength of this department and makes us really unique.”

A Legacy of Innovation and Student-Driven Research

Collinger arrived at Pitt in 1999 when she joined one of the earliest cohorts of undergraduate students in the bioengineering department. Her passion for biomechanics and rehabilitation ultimately led her to the bioengineering department’s PhD program, and since graduating, she’s been working at the university . As a former Pitt Bioengineering student herself, Collinger credits current students in the department for pushing cutting-edge neural engineering research forward each day. 

“Graduate and undergraduate students design studies and collect and analyze data; they are doing the work and driving the science forward,” Collinger said. “They are also great at helping us connect with other happenings in the department. That often evokes who we might be able to collaborate with or who we can ask about a particular challenge that we are having in the laboratory.”

Since its inception in 1998, Pitt’s Department of Bioengineering has grown from just four faculty members and a handful of students to more than 200 faculty members (45 primary and 158 secondary) and thousands of alumni. For Batista, one of the first neural engineers hired in the department, watching these novel breakthroughs emerge has been nothing short of spectacular. Having seen the department grow in both size and scope throughout the years, Batista credits the University’s physical environment and culture for fostering the essential collaborations that have cemented Pitt as a hub for neural engineering innovation. 

“The physical and intellectual environment here really sets us apart from other universities,” Batista said. “The fact that Pitt’s schools of medicine, rehabilitation sciences, and engineering are just minutes away from each other, our proximity to Carnegie Mellon University, and our leadership that fosters a culture of collaboration helps brain research at the University flourish."

.

In addition to studying in the Swanson School of Engineering and David C. Frederick Honors College, Bhargava works as a student researcher in the Visualization and Image Analysis Laboratory, led by Professor George Stetten.

There, he is developing an algorithm for software designed to help researchers better visualize and analyze the brain’s blood vessels. The tool processes MRI images to map vascular structures and track changes in blood flow throughout the brain, a process known as brain vessel segmentation. This flexible research instrument could enable scientists to explore a wide range of questions about how diseases like Alzheimer’s progress. By improving the way researchers extract and study vascular data from brain scans, Bhargava’s algorithm could support studies comparing changes across age groups, genders, or stages of the disease.

For now, the technology is primarily geared toward research use. But with his work, for which he has also received a Frederick Honors College research fellowship and health sciences research fellowship, Bhargava hopes it could eventually contribute to developing early detection methods and better treatment strategies for neurodegenerative diseases.

“I think one of the biggest reasons why I love doing this research is its potential for a really broad impact on Alzheimer’s disease,” said Bhargava. “And to attack the problem, not by looking at some specific aspect of it, but by creating a solution that enables a lot of different research to be done on Alzheimer’s disease, that’s what really draws me into it and keeps me engaged with it.”

Bhargava is among 441 college juniors and seniors nationwide selected for the scholarship, which was established by Congress in 1986 to honor the legacy of U.S. Senator Barry Goldwater and support students who intend to pursue research careers in STEM fields.

“Satyaj exemplifies the very best of our honors community — intellectually curious, deeply committed to advancing human health and always seeking opportunities to make a meaningful impact,” said Nicola Foote, dean of the Frederick Honors College. “His recognition as a Goldwater scholar reflects not only his exceptional research accomplishments, but also his passion for discovery and his dedication to improving lives through science.”

Bhargava says his research journey has been bolstered by the continued support of his family and guidance from several mentors at Pitt, including Professor Stetten; James Wang, a professor of bioengineering in the Swanson School; and Josh Cannon, director of research at the Frederick Honors College. Outside of the lab, Bhargava also balances a vibrant musical life as a lead percussionist for the Pitt Symphony Orchestra.

Bhargava credits his lab mates and the collaborative environment at Pitt for helping him reach this milestone, adding that receiving the Goldwater Scholarship felt like a confirmation of all his hard work.

“I think with research, it's one of those fields where a lot of the times the work you put in doesn’t always pay off,” he said. “So, to see all the work that I did put into this research project pay off and be recognized by such a prestigious and honorable award, it was a testament to all the work that I put into this project.”

Looking ahead, Bhargava plans to pursue an MD/PhD in biomedical engineering, with the goal of becoming both a practicing surgeon and a research scientist. He hopes to continue exploring ways engineering innovations can transform medical diagnoses.

“A Neuropathology Case Report of a Woman with Down Syndrome who Remained Cognitively Stable: Implications for Resilience to Neuropathology,” a new publication in Alzheimer's & Dementia: The Journal of the Alzheimer's Association (https://doi.org/10.1002/alz.14479), found an unexpected Alzheimer’s disease progression in an woman with Down syndrome. 

For ten years, a woman with Down syndrome participated in the Alzheimer Biomarker Consortium - Down syndrome Research Study (ABC-DS) with a team of investigators including Elizabeth Head, professor in the department of pathology and laboratory medicine at the University of California, Irvine. At the time of her passing, investigators were grateful for her gift of brain donation, and her brain was shared with the University of Pittsburgh’s 7T Bioengineering Research Program radiofrequency research facility, where Jr-Jiun Liou, postdoctoral scholar in the department of bioengineering, imaged her brain using the team’s high-resolution 7 Tesla MRI scanner. 

“We are interested in trying to link neuroimaging with neuropathology, because we want to use information from neuropathology datasets to inform diagnostic and therapeutic criteria for individuals with Down syndrome before they pass away,” Liou said. 

The final neuroimages that Liou reviewed surprised her. Although the participant was cognitively stable at the time of death, MRI imaging revealed the presence of neuropathology indicative of Alzheimer’s disease in her brain. This finding highlighted a discrepancy between her lived experience and clinical diagnosis compared to her underlying biological pathology.

“Before she passed away, all the clinical assessments in our years of studying her indicated that she was cognitively stable, which is why this case is so fascinating,” Liou said. “Despite her brain’s pathology indicating Alzheimer’s, we think that her cognitive stability could have been attributed to her high education level or underlying genetic factors.”

Liou and Head hope that this case study will help improve existing diagnostic tools and expand the inclusion criteria for therapeutic drug trials targeting Alzheimer’s disease and dementia. Clinical trials typically have narrow criteria for acceptance, but if more individuals with this type of “hidden” pathology for Alzheimer’s are included, the treatments could become more effective.

The data also presents a rare opportunity to uncover genetic or lifestyle factors that may contribute to cognitive preservation—insights that could ultimately benefit not only individuals with Down syndrome but the broader population.

“If we can identify the genetic underpinnings or lifestyle factors that allowed her brain to function well despite the pathology, we may uncover strategies that could benefit others,” Head said. “This study shows how just one person’s participation in research can lead to profound discoveries.”

Praveen Kumar, Department of Health Policy and Management
Bo Zeng, Department of Industrial Engineering 

The administration of blood transfusions by paramedics to patients with life threatening injuries while enroute to the hospital – prehospital transfusion – has been introduced in emergency medical service systems (EMS) in several U.S. cities. Evidence indicates that prehospital transfusion helps to improve survival, especially when transport is delayed by heavy traffic or entrapment after a car accident, for example. Through a multidisciplinary collaboration, Kumar and Zeng will use a large EMS dataset to determine how to expand access to this lifesaving treatment and identify a cost-effective approach that can be sustained to save more lives.

Andrea Rosso, Department of Epidemiology
Mark Redfern, Department of Bioengineering 

Assessing the walking patterns of older adults in their everyday environment has been used increasingly to identify potential fall risks related to dementia or Parkinson's disease. Known as free-living gait evaluation, this approach has been limited by available technology. Rosso and Redfern will develop and test wearable products that will combine mobile technologies and global positioning systems to measure both gait and location simultaneously. Their hope is to improve the ability to predict individuals who could be most at risk for falls.

Lisa Parker, Department of Human Genetics 
Takashi Kozai, Department of Bioengineering 

Research on neural prostheses, devices that can substitute for impaired motor, sensory or cognitive functions, such as Cochlear implants, require participant-provided data, but also present challenges related to privacy and consent. By integrating patient input on data collection with advanced analytic methodologies, Parker and Kozai aim to transform neural prosthetic research. Their approach seeks to empower participants to contribute to data collection design, analytic tools and training resources, ultimately bridging the gap between technical development and participant engagement.

Rebecca Deek, Department of Biostatistics and Health Data Science 
Bistra Iordanova, Department of Bioengineering 

Routine and cost-efficient ways to screen people at high risk of developing neurological diseases, such as dementia, are challenging because much remains unknown about how and when brain changes occur that heighten individual risk. In current clinical studies, the link between specific gene expressions and how brain cells may be affected over time is uncertain. Deek and Lordanova propose to combine brain imaging with omics datasets - a collection of data that describes the molecular makeup of an organism – through techniques that break data down into simpler components. This will help the researchers note highly correlated features across modalities and data, and, in turn, determine the predictive capability of their approach.

Ying Ding, Department of Biostatistics and Health Data Science
Wei Gao, Department of Electrical and Computer Engineering

Respiratory diseases such as asthma and chronic obstructive pulmonary disease are widespread. Despite advancements in medical treatments and interventions, severe outcomes remain frequent, leading to emergency department visits or hospitalizations. Ding and Gao will use a smartphone-based system – Smartphone Ultrasonic Respiratory Evaluation – to measure chest wall mobility, which is strongly correlated with lung function, breathing patterns and the severity of symptoms. This system can potentially improve early diagnosis and provide a cost-effective, portable respiratory evaluation tool for detecting, diagnosing and managing chronic respiratory diseases.

Aaron Batista, professor of bioengineering at Pitt’s Swanson School of Engineering, with long-time collaborator Byron Yu, professor of electrical and computer engineering and biomedical engineering at CMU, expanded their BCI research to provide empirical evidence that neural population activity is constrained to follow specific sequences. Their results, “Dynamical constraints on neural population activity,” were published in the February issue of Nature Neuroscience.

Batista and Yu, leading researchers in BCI, explained that a fundamental principle in neural dynamic models assumes that neural activity sequences in the brain are as rigidly defined as a roller coaster. Like a roller coaster ride, neural activity can only move forward along its path, apparently without the ability to readily go backward or jump the rails. Although this theory has laid the groundwork for the development of complex artificial intelligence models in use today, it had never been directly tested— until now. 

“Our findings are a direct causal test of ideas that have shaped the field of neural dynamics,” Batista said. “We used BCI technology to challenge our subjects to deviate from these neural sequences and found that it was nearly impossible for them to do so.”  

Batista’s team leveraged BCI technology to provide Rhesus monkeys with real-time feedback of their own neural activity. The subjects were then prompted to use their minds to move a cursor on the screen in front of them in different directions, in ways that both followed the natural sequence of activity and in ways such as backwards or sideways that diverged from these standard sequences. Even after extended practice, the team found that the subjects lacked the flexibility to move the cursor in different ways, which demonstrated that neural activity in the brain is in fact constrained to predefined computational paths. 

According to Yu, interdisciplinary research between engineering and neuroscience has helped to advance our understanding of the brain. BCI in particular has enabled researchers to examine in real time how its complex neural structure enables human and non-human primates to function. 

“We combined experimental and computational neuroscience together every step of the way in this project.” Yu said. “Starting off with a common scientific goal from day one and then working together on all levels of the project leads to science that could not have been done with either of our groups alone.”

Since these neural activity sequences are fundamental to countless functions in the brain, the team sees their discovery as a launching point for leveraging this knowledge in a broad scope of applications in the future. 

“If the brain operates in this particular way, we can then understand its mechanisms to leverage them.” Batista said. “This knowledge can help us shape future therapies, stroke rehabilitation, or build better brain-computer interfaces.”

Read more from Carnegie Mellon University.

This work was co-authored by Alan Degenhart and Emily Oby, former Pitt Bioengineering postdoctoral researchers, former Pitt bioengineering graduate students Erinn Grigsby and Patrick Marino, postdoctoral researcher Asma Motiwala, and PhD candidate Nicole McClain.

Helen Schwerdt, assistant professor of bioengineering at Pitt’s Swanson School of Engineering, received a five-year, $2.5 million R01 award from the National Institutes of Health (NIH) to study dopamine’s role in learning. Schwerdt’s team develops novel multimodal neural interfaces to understand how the brain and pathological mechanisms work and to improve treatment of debilitating neurological disorders.

 “We’re interested in developing technologies to measure molecules in the brain, and figuring out how to optimally combine these types of molecular measurements with the conventional electrical measurements that we typically use to look at brain activity.” Schwerdt said. “Communication between neurons occurs both electrically and chemically, but the chemical aspect is less understood because we haven't had the right tools to measure these signals together.”

Dopamine is a neurotransmitter found in the brain that plays a role in many body functions, including memory, movement, motivation, mood, attention and more. Schwerdt plans to investigate the lesser-known role of dopamine in learning, especially its connection to learning from punishment, which has received less attention compared to its role in reward systems.

“Reward is very important, and it’s an incentive for us to learn new things. But in real life, we commonly learn from negative incentives as well.” Schwerdt said. “The question is, how does the brain handle these two different types of incentives — is it the same circuits and the same neurons that handle both reward and punishment, or are they different?”

Schwerdt’s team has developed a method for sustained dopamine monitoring by implanting neural interfaces in Rhesus monkeys. Monitoring dopamine in the brain for years at a time will help the team measure dopamine’s impact over the course of learning, and dispersing the sensors in different areas of the brain will help the team assess how dopamine levels fluctuate differently in different brain areas. 

 “We fabricate the sensors in our lab, and when we implant them, we disperse the sensors all across the striatum, because the dopamine appears differently depending on where you record it in the brain.” Schwerdt said. “I believe that a lot of important past studies support the idea that the punishment-related dopamine signals are going to be in different areas of the brain than the reward-related signals.”

Once the neural interfaces are implanted, the team will test the monkeys with a set of trial and error learning tasks to examine how the dopamine behaves in real time. This will allow the team to learn if certain areas in the striatal brain region produce negative punishment related signals and assess how the signals evolve during the course of learning. 

This project could eventually lead to a baseline standard that reveals how dopamine is behaving across the primate striatum during important cognitive behaviors. Studies of humans with Parkinson’s disease have shown impairments in learning from rewards and punishments, and Schwerdt hopes that these findings can also be translated into better understanding the disease, where dopamine dysregulation is a major factor. 

 "In the future, I would like to test these behaviors in a model of Parkinson's disease so we can study how dopamine signals in the striatum change and how these changes contribute to behavioral symptoms.” Schwerdt said. “I'm particularly interested in exploring how these dopamine signals could be used as biomarkers to guide future treatments."

Gelsy Torres-Oviedo, associate professor of bioengineering at Pitt’s Swanson School of Engineering received a five-year, $5.3 million R01 award from the National Institutes of Health (NIH) National Institute on Aging (NIA) with interdisciplinary co-investigators Helmet Karim, assistant professor of psychiatry and bioengineering; Andrea Rosso, associate professor of epidemiology; Gong Tang, professor of biostatistics; and Andrea Weinstein, assistant professor of psychiatry. 

Their project, “Neural Mechanisms Underlying Cognitive Contributions to Walking as an Early Marker for Risk of Alzheimer’s Disease and Related Dementias,” will study the correlation between walking and mild cognitive impairment (MCI). The team hopes to unveil neural mechanisms underlying the relation between mobility and cognitive decline to enhance early ADRD risk prediction. 

“Assessing someone who is at risk of developing dementia is difficult, it's not very clear cut, and the existing tests are often not enough to identify whether someone is at risk of cognitive decline.” Torres-Oviedo said. “But mobility could be a potent predictor, and just having someone perform a walking task could eventually help clinicians better classify those who are at risk for dementia.” 

The study will begin by screening research participants for MCI, a condition defined by mild levels of cognitive decline such as memory loss and trouble with language and judgment, but does not typically interfere with daily life. Not all people with MCI develop ADRD, but according to Andrea Weinstein, it’s a useful research diagnosis because people with MCI have a greater risk of developing dementia. 

“When you wait until someone has been diagnosed with dementia to start treating them, they're already fairly far along in the disease, so a lot of research has moved toward intervening at the MCI stage instead.” Weinstein said. “We want to look at locomotor learning in people with MCI and assess whether we can kind of see their neural efficiency and ability to adapt to new walking patterns.” 

To study this, participants with and without MCI will perform a walking task on the Sensorimotor Learning Laboratory’s split-belt treadmill, which moves each leg at different speeds to challenge participants to adjust their gait. After a few recurring visits, Torres-Oviedo can then analyze the muscle activity and leg movements to track how both groups of individuals adapt to these changes over time. 

“When you're walking in a new environment like the treadmill, you’ll feel off balance at first, but the motor system eventually adjusts and learns how to walk under these circumstances,” Torres-Oviedo said. “Healthy older adults show a greater locomotor learning index—they learn a new motor memory and retrieve it the next time they’re in the lab. But for people with mild cognitive impairment, this ability is diminished.”

The group hypothesizes that the diminished locomotor ability in individuals with MCI could be related to dysfunction in the basal ganglia, a cluster of structures at the center of the brain that impacts mobility and cognition.

“This link in the brain between cognition and motor performance is incredibly important,” Weinstein said. “The basal ganglia has interconnected loops throughout the brain that are involved not just in motor systems, but also in cognitive control. We’ve been working together for a long time to emphasize thinking about cognition and motor performance together, because they're all resulting from the central nervous system.”

Looking ahead, solidifying and understanding this link between mobility and MCI could eventually help clinicians more efficiently identify individuals at risk for ADRD and even help aging individuals without dementia maintain their independence, according to epidemiologist and collaborator Andrea Rosso. 

“Ultimately, I really want to help people maintain independence— like making sure they can get out the door and grocery shop or be with their family.” Rosso said. “Understanding what mechanisms are behind reduced mobility and why it may be more common among people who are at risk of dementia can help us create interventions that will help them. Whether that's directly targeting brain health, or even using physical therapy, we want to help reduce fall risk and maintain their mobility.”

“To put it into perspective, that’s two Heinz Fields’ worth of people who die every year from opioid overdoses,” said Trent Emerick, associate professor in the departments of anesthesiology, perioperative medicine and bioengineering. Along with appointments in the School of Medicine and Swanson School of Engineering, he directs Pitt’s Pain Medicine Fellowship Program.

Emerick has a host of tools at his disposal when it comes to treating pain, but some of the most effective — and most intrusive — methods come with a host of side effects and potential complications.

“I wanted to develop something a little longer lasting than a nerve block, but not something as risky as the permanent implants that have a lot of risks and side effects,” Emerick said. With the help of two Swanson School of Engineering researchers, he came up with a solution: “a bioabsorbable, or biodegradable, nerve stimulator.”

The invention has earned the researchers multiple internal grants, which yielded enough preliminary research to secure National Institutes of Health funding. The team earned a Helping End Addiction Long term (HEAL) grant as well as a Small Business Technology Transfer (STTR) award, which required the team to start a company so they could bring their final product to market.

“We call it Vanish Therapeutics Inc. because [the stimulator] dissolves in the body.”

Finding what works for persistent pain

When pain persists for three months, it’s classified as chronic. At that point, “The spinal cord and brain can become overactivated and the pain itself starts to take on a life of its own outside of the original site of tissue injury,” Emerick said. As the pain worsens, many of patients are ultimately seen by physicians in primary care, surgery or pain management specialties. But these pain syndromes can be difficult to treat, and while doctors prescribe opioids to help, the drugs are often not effective and present significant side effects, including tolerance, dependence, misuse and opioid use disorder.

Extreme options like implanted devices tend to work extremely well, Emerick said, but even if they eliminate the pain, they’re problematic.

“If the pain gets better, now the device is stuck in the body. If it gets infected, it has to be removed,” he said. It’s a risky, not to mention expensive procedure. In some cases, implanted devices can even lead to more pain. “The overall complication rate with all of these risks combined is 30%-40%.”

But the nerve stimulator not only dissolves in the body as pain improves over a predetermined period of time, but if for any reason a person is unhappy with it, the battery can be adjusted to emit a specific waveform that will quickly break down the stimulator: “degradation on command,” according to Emerick.

From researchers to entrepreneurs

To mitigate the risk while still providing the kind of pain relief that implants offer, Emerick reached out to the Swanson School’s Center for Medical Innovation. “I asked if they had anyone who could help me develop something that would dissolve. I didn't know if that was a fairy tale or something that could really happen.”

He heard from Xinyan (Tracy) Cui, William Kepler Whiteford Professor of Bioengineering, who has a background in chemical engineering, materials sciences and biophysics. “My research is in this interdisciplinary field where we are using engineering and materials science to help develop implantable devices,” she said. She’d done work with biodegradable metals and polymers in the past. “So I thought, OK, I can help.”

Her graduate student at the time, Kevin Woeppel, had been working on developing materials for drug delivery and preventing electrodes from triggering adverse immune reactions. Emerick had found the perfect research partners.

They also turned out to be great entrepreneurial partners. Cui has filed many invention disclosures and has had a patent licensed, though Vanish Therapeutics is her first startup.

Like Emerick, this was Woeppel’s first foray into the entrepreneurial space, though even as a student, he had expressed interest. “I really enjoy being on the research side of things,” he said. “I just wanted to see what taking it one step further would be like.”

Cui said she hears this from students often, “It's not uncommon for a student at that age or stage of their career to try to explore more things,” she said. “They want to know what is best for them.” It turned out, reaching out to the Office of innovation and Entrepreneurship (OIE) was the best move for them all.

Filing an invention disclosure with OIE in 2020 led to the team’s participation in the NSF I-Corps program, which paired them with a mentor who helped them develop a business plan. They also received funding through the Clinical and Translational Science Institute and, as a student, Woeppel, now a biosafety engineer at Philips Respironics, won the Michael G. Wells Student Healthcare Competition.

Startups beget startups, and Emerick is not only mentoring others but is also thinking about the next project.

“There were multiple times where I hit what seemed like a dead end,” he said. “But maybe part of the process is, if you have a decent idea, it will keep coming back if you keep working on it.”

Every professional who functions at a high level of performance knows the value of keeping things loose during harrowing tasks. Choking under pressure, or being unable to perform to one’s highest standard when it matters most, is an undesirable alternative. While athletes are often associated with this phenomenon, people choke under pressure in many settings, for example, test-taking, giving presentations, puzzle-solving, and beyond. New research from Carnegie Mellon University and the University of Pittsburgh reveals a first-of-its-kind neural explanation for choking under pressure: a deficit in motor preparation induced by an overly large potential “jackpot” payoff.

To study how motor performance is impacted by choking under pressure, researchers recorded the spiking activity of hundreds of motor control neurons in Rhesus monkeys, who were trained to perform a challenging task to earn rewards of varying sizes. When an unusually large jackpot reward was at stake, the animals underperformed, leading the group to examine how cued rewards modulated neural population activity during movement preparation.

“By looking at the activity of populations of neurons in the motor cortex, we found a signature of choking under pressure, that at the precision of 100s of milliseconds, was indicative of whether or not a subject would fail in an upcoming trial,” explained Adam Smoulder, a graduate student at Carnegie Mellon and first author of the Neuron paperOpens in new window. “Through a series of three hypotheses, we sought a more mechanistic explanation of choking under pressure. We found that rewards interact with target preparation signals to drive neural activity toward a region associated with improved reach execution, and then, at the highest rewards, spread away from this region. So, it seems that increasing motivation by offering larger rewards can improve the discriminability of the neural signals, but only up to a point. Beyond that point, we actually see a collapse in neural information, and that’s tightly correlated with when the animals choke under pressure.”

This nuts-and-bolts level of explanation differs from previous, more holistic work, due to its high-resolution nature, and ability to consider the activity of populations of neurons, versus either the aggregate activity which can be seen with fMRI, or prior work in which only the activity of individual neurons was available.

“It’s hard work to take something that everybody has an intuition about and relate it to neural activity,” noted Aaron Batista, professor of bioengineering at the University of Pittsburgh. “Our data indicates that subjects seemed to become overcautious, self-monitoring to their detriment when the jackpots were offered. If people trying to avoid choking under pressure were to benefit from our study, we suggest they could beat it by finding the right balance between self-awareness and self-control, and just generally keeping it loose when the stakes go up, even if there is a natural tendency to clamp down.”

In terms of helpful application, the group believes that knowing what’s going on in your brain can help people with coping and mitigating the risks of choking under pressure.

“Choking under pressure is a really interesting example of when the brain gets it wrong,” added Steve Chase, professor of biomedical engineering at Carnegie Mellon and the Neuroscience Institute. “Now that we understand a little bit about how the brain is failing under these high reward situations, we want to try and correct it. One way to do this would be to design techniques that leverage our combined brain-computer interface (BCI) experience to encourage the brain not to do those things and ultimately, rescue the behavior.”

The group’s work is ongoing and done in collaboration with the Center for Neural Basis of Cognition, a cross-university research and educational program between Carnegie Mellon and the University of Pittsburgh that leverages each institution’s strengths to investigate the cognitive and neural mechanisms that give rise to biological intelligence and behavior.

Published in a recent issue of the journal Blood, the study also identified a protein that may protect against kidney disease in mice and patients, suggesting it has potential as both a biomarker to identify at-risk patients and as a novel target for new therapeutics.  

“Patients with sickle cell disease have a life expectancy of just 50 to 55 years, almost two decades less than the general population,” said senior author Dr. Samit Ghosh, assistant professor in the Department of Medicine and member of the Vascular Medicine Institute at Pitt. “Chronic kidney disease is a major contributor to mortality in these patients, so there is a huge need to better understand the mechanisms driving disease and develop new therapies.” 

SCD patients produce a flawed version of hemoglobin, the protein in red blood cells that carries oxygen around the body, that is shaped like a crescent, or sickle, instead of a round disc. These stiff, sticky cells block blood flow by clumping together and are prone to breakage, or hemolysis, which results in heme leaking into the bloodstream. 

“When heme is inside red blood cells, it’s essential for carrying oxygen to different tissues around the body,” explained Ghosh. “But when heme is released out of the cell via hemolysis, it’s toxic to organs and tissues.” 

To learn more about how hemolysis contributes to kidney disease, Ghosh and his team used a mouse model of SCD that expresses human sickle hemoglobin. They infused the animals with heme repeatedly over time to mimic ongoing hemolysis that occurs in SCD patients.  

Dr. Kang Kim, professor in the Department of Bioengineering and Department of Medicine at Pitt and member of Pitt’s Vascular Medicine Institute and the UPMC Heart & Vascular Institute, and first author Dr. Qiyang Chen, postdoctoral associate in Dr. Kim’s Lab, then used a novel super-resolution ultrasound imaging to non-invasively measure the extent of vascular damage in the animals. 

They found that repeated exposure to heme led to damage of the renovascular endothelium, the layer of cells lining the kidney’s blood vessels, and renal failure. The findings suggest that ongoing hemolysis, experienced by SCD patients, drives chronic kidney disease. 

Delving deeper, the researchers found that a protein called EPCR was cleaved from the surface of endothelial cells in response to heme. As a result, these mice had more EPCR in their bloodstream.  

Blood levels of EPCR were also elevated in SCD patients with chronic kidney disease, mirroring the results in mice.  

“Our findings suggest that blood levels of EPCR could act as a potential biomarker of chronic kidney disease in patients with SCD,” said Ghosh. “If we can predict who is at greater risk for kidney disease, we could treat these patients earlier to help prevent disease progression.” 

It’s not clear how heme causes EPCR to detach from the cell surface, but Ghosh has several hypotheses that he plans to investigate in future research.  

“Different people seem to have different degrees of EPCR stability,” said Ghosh. “Some have EPCR that is harder to cleave from the endothelium, and we hypothesize they may be more protected from kidney disease than those with EPCR that is more easily detached. We are now planning to test this.” 

Using mice that overexpressed EPCR, the researchers found that the protein protected animals from heme damage. 

According to Ghosh, these findings suggest that drugs or gene therapies that induce higher levels of EPCR in the endothelium could potentially be a new approach for treating or preventing chronic kidney disease and damage to other organs in patients with SCD. 

A collaboration between University of Pittsburgh bioengineers and a medical technology company may bring us one step closer to measuring human brain activity more efficiently - and potentially benefit people with nervous system injuries as well as improve artificial intelligence. 

Takashi D.Y. (TK) Kozai, Associate Professor of Bioengineering and Ernest E. Roth Faculty Fellow, works to improve the long-term performance of implanted electrodes and integrate technology with the human brain to study nervous systems in vivo at the cellular level. For the past five years at Pitt’s Swanson School of Engineering, he’s worked with Actuated Medical to enhance the biocompatibility of implanted devices in the brain. Their findings, "Low-intensity pulsed ultrasound stimulation (LIPUS) modulates microglial activation following intracortical microelectrode implantation,” were recently published in Nature Communications.

“When you implant devices in the brain, the brain recognizes them as a foreign body and tries to wall it off with glial scars, which prevent brain signals from reaching the electrode itself,” Kozai said. “Reducing glial scars would improve the electrodes’ effectiveness and provide clearer scans of brain activity.”

During the project, Kozai’s team investigated the effects of using low-intensity pulsed ultrasound stimulation (LIPUS) on microglial activity to measure its impact on the performance of chronically implanted microelectrode arrays. After testing this technology on mice and rats, Kozai’s project was a success — by using the ultrasound technology to gently massage the tissue around the electrodes, glial scar tissue didn’t build up around the implant, which vastly improved the signals that the team was able to receive from the electrodes. 

“These findings give us a new lever to push and pull in terms of understanding the brain,” Kozai said. “We want to implant these devices to be able to record the brain activity, and by recording the brain activity, we can eventually learn how to treat motor function in people who have spinal cord injury or work to treat vision in patients who are blind.” 

Actuated Medical developed the SonoShield Defender, the ultrasound transducer used by Kozai's team, and performed their own longitudinal electrophysiology experiments in parallel with the Kozai lab’s imaging experiments. According to Actuated Medical President and CEO Maureen L. Mulvihill, the success of this project is a significant breakthrough that will enable other neuroscience researchers to use SonoShield Defender in preclinical models. 

“We developed this prototype, TK tested it in his work, and it performed well, so now we're going to commercialize it so that other researchers have the ability to use this technology,” Mulvihill said. “We’re now looking at multiple applications for non-invasive ultrasound to help reduce cell damage in the brain and elsewhere in the body.”

For Grace Hwang, program officer at the National Institutes of Health (NIH) Brain Research Through Advancing Innovative Neurotechnologies® Initiative (The BRAIN Initiative®), Kozai’s project supports their goal to enable researchers to improve how we treat, prevent, and cure brain disorders through a detailed understanding of the brain. 

“These results highlight the versatility of ultrasound as a non-invasive tool, with potential to enhance the efficacy of other, more invasive interventions,” Hwang said. “The present study aligns well with the mission of The BRAIN Initiative to revolutionize our understanding of the human brain.”

Looking ahead, Kozai also hopes that this technology will enable further research modulating different types of brain cells that can prove useful for cell therapy or for building more energy efficient artificial intelligence. 

“These findings open the door for looking at non-neuronal cell activity with our two-photon microscope using ultrasound. If we can modulate those, likely we can modulate many of the other types of non-neuronal cells in the brain,” Kozai said. “These cells all play an important role in neural network activity that has been underappreciated both from a cell therapy perspective as well as with bio-inspired artificial intelligence.”

Xinyan (Tracy) Cui, professor of bioengineering at the Swanson School of Engineering, and Amy Wagner, a neurorehabilitation physician and neuroscientist in the department of physical medicine and rehabilitation, received a 5-year, $2.65 million R01 grant from the National Institutes of Health (NIH) for their project “Investigation of Cognitive and Affective Deficits Post TBI Using Multimodal Flexible Neural Probes.” 

“With this grant, we want to understand the brain’s neurochemistry after TBI and look at two neurotransmitters: dopamine, which is known to relate to some post-TBI symptoms, and glutamate, an excitatory neurotransmitter that has been found to increase after a traumatic brain injury,” Cui said. “We want to make a tool that can measure both of these neurotransmitters while specifically looking at their concentration in the striatum region of the brain.”

Traumatic brain injury can be mild, moderate, or severe, and is frequently caused by car accidents, falls, sports, or explosions. TBI can cause cognitive or emotional deficits such as memory loss and depression - while dopamine stimulants have proven effective in treating these deficits, the reason why this treatment works is still unknown.

 Neurotransmitters such as dopamine and glutamate allow neurons to communicate with each other throughout the body. To understand how clinicians can better treat TBI and its symptoms, Cui's first aim in this project is to develop a multimodal microelectrode array (MEA) tool that measures developing neurotransmitters. 

“Currently, there is no tool available to measure neurotransmitters as they develop,” Cui said. “We want to develop such a tool, which will allow us to measure the electrical activities of the neurons and neurotransmitters in the same region simultaneously to help us understand neural transmission and how the neurotransmitters change as the injury evolves.” 

MEAs contain multiple microelectrodes that monitor neural signals in the brain, and serve as neural interfaces that connect neurons to electronic circuitry. Once their MEA is developed, the team will then correlate the findings with actual behavior outcome post-TBI and observe how the neurotransmitters relate to different behavior deficits.  

“We are using an engineering approach to develop previously unattainable tools that will help neuroscientists better understand neuroscience and also help doctors understand and come up with new treatments,” Cui said.

Overcoming Challenges in Studying TBI

Most existing tools that monitor neurotransmitters fail after a short time period, lasting from just a few hours to about a day, and currently, there’s no tool that can measure both neural activity and neurotransmitters in the striatum for an extended period of time. Cui’s project aims to combat this by developing a longer-lasting tool that will be able to withstand deterioration for three weeks inside the brain. 

“We have spent a great deal of time improving the sensitivity and stability of the sensor while trying to understand how the in-vivo environment affects the sensor, damages it or causes it to be sensitive,” Cui said. “We’re now taking some of those results from past research and applying them to our new tool to improve sensor longevity.”

Another challenge in studying TBI is the fact that the injury shrinks and swells over time, which Cui’s team is adapting to by developing a MEA that can adapt to the changing injury. 

“A specific challenge with TBI is that as the injury occurs, it's a mechanical impact, and then as the injury develops, there'll be a lot of swelling of the tissue, so a stiff device is not going to accommodate that kind of swelling and shrinkage,” Cui said. “Our device is very flexible so that it can basically maintain its electrical connection and integrity during the deformation of the tissue.”

The project will also begin at a pivotal moment in the world of neuroscience research—the BRAIN initiative, a key program supporting neuroscience research in the United States, faced a 40% cut in funding this fiscal year, with many researchers uncertain about the likelihood of future projects receiving funding. 

“I feel especially fortunate that we got this grant since the NIH is cutting funding dramatically,” Cui said. “I hope that people can realize this type of research is important and that we should have more funding coming into any kind of medical health related research.” 

Depending on the severity of the injury, those with TBI may face health problems that last just a few days or for the rest of their lives. Outcomes from this project will have broad implications from both design and scientific standpoints, and Cui hopes that her work will ultimately help create more personalized treatments for patients with an array of neurological conditions. 

“From the scientific outcome perspective, we will have a better understanding of the mechanisms behind cognitive and emotional deficit post-TBI, so we will be able to have a more customized drug treatment to treat our patients.” Cui said. “And along with TBI, the tool that we develop can be used for a variety of neuroscience research, including depression, schizophrenia, and drug addiction.”

Takashi D-Y Kozai was the kind of kid who loved robots and dreamed of becoming an engineer. But a scientist? Not so much. “Biology class was just taxonomy, memorization, and labeling stuff,” says the associate professor of bioengineering at the University of Pittsburgh Swanson School of Engineering.

That changed in high school, when Kozai learned about adenosine triphosphate (ATP) synthase, the turbine that assembles the basic biological unit of energy that powers everything from bicep flexes to nerve impulses to the beating of your heart. WOW, he thought. Okay. Biology is the smallest and most energy efficient piece of engineering that exists in this world.

Kozai completed not one but two life sciences BAs—one in molecular, cellular, and developmental biology and another in biochemistry—at University of Colorado, Boulder. There, he first dipped his toe into basic science research, in a neuroscience lab. One experiment in particular became another turning point. 

He was trying to grow neurons onto cell-culture electrodes—and it wasn’t going well, because of the way the materials were designed. Exasperated, he complained to his advisor: Why do they make these things so hard to use? His advisor’s response was, essentially: Because engineers don’t understand biology. 

That got Kozai’s gears spinning. He pivoted back to the engineering-curious kid in him, pursuing both an MA and PhD in biomedical engineering at the University of Michigan. 

Kozai came to Pitt as a bioengineering postdoc in 2011 and eventually would found his own lab, focusing his research on cellular mechanisms of the brain in the context of, among other things, brain-computer interface (BCI).

Test runs of BCI have made headlines in recent years, enabling people with paralysis to use robotic limbs controlled by their thoughts. Unfortunately, bringing BCI into reliable and sustainable everyday use has proven challenging; the body’s reaction to the electrodes implanted within the brain gradually degrades the devices’ performance over time. 

In Kozai’s most recent work, he’s showing that a non-neural cell called oligodendrocytes—which are under-researched in his subfield—could be instrumental to solving this puzzle. This spring, Kozai was awarded a $3 million R01 grant from the National Institute of Neurological Disorders and Stroke to continue making power moves in this area.

While Kozai enjoys keeping one foot in each of his favorite disciplines, the tradeoff is he doesn’t exactly fit the mold for either. Biologists don’t really claim him as one of them, he says, “and to a hardcore engineering group, I'm not really considered an engineer.” 

As an Asian American, he’s no stranger to feeling like… well, a stranger. “If I go to Japan, they’ll say that I'm a foreigner. And if I'm in America, they'll say I’m not really white,” he says. He was also the lone economically disadvantaged student in the private school his mom struggled to put him through growing up. “I was taking classes with a bunch of rich kids, but not living that lifestyle.” A couple times, the lights went out at home. 

But the kid who grew up outside of the in-group is now the scholar confounding categories, and he has come to enjoy living between the lines. Freedom from group-think and all the hype over headlining science (“optogenetics, the brain-gut access, whatever the flavor of the year might be”), opened his eyes to new possibilities, he says—like a little-understood cell type with secrets to tell.

Kozai takes inspiration from a quote he once read in the New York Times, from Yoshinori Ohsumi, 2016 Nobel Prize in Physiology or Medicine winner who discovered a cellular process known as autophagy: I am not very competitive, so I always look for a new subject to study, even if it is not so popular. If you start from some sort of basic, new observation, you will have plenty to work on.

“To me,” says Kozai, “it’s about: What are the problems that are being overlooked?”

In 2020, with funding from the National Science Foundation, Kozai founded eBioNIC.org, a virtual community promoting diversity in his field. He believes different perspectives—in academic discipline, ethnicity, and economic background—is a powerful igniter for discovery. That principle guides him in both his classroom and his lab.

“There are occasionally some students that come up to you, like, Why don't you just tell me what you're thinking? But I need to know the things that I'm not thinking, right? That's how we build a stronger collective of perspectives, problem-solving approaches, and solutions.”

Photography by Tom Altany/Pitt Photography

“There are two major challenges,” says Takashi (TK) Kozai, associate professor of bioengineering at the University of Pittsburgh Swanson School of Engineering, who leads the BIONIC Lab (Bio-Integrating Optoelectric Neural Interface Cybernetics). For one, over time, scar tissue forms around the electrodes, which complicates the signal’s path to the nearest neuron and dampens the voltage. And for another, there’s a lot of variability in performance. 

“Sometimes these devices work, and sometimes they don't,” he says. 

Overcoming these challenges will be a formidable feat from both the engineering and neurobiology perspectives. Luckily, Kozai lives right at the nexus of the two.

In May, Kozai was awarded $3 million R01 grant over five years from the National Institute of Neurological Disorders and Stroke. The focus of the project is to gain a better understanding of a specific cell type, called oligodendrocytes, which he believes could play a key role in settling this unique human-versus-machine dilemma. 

Oligodendrocytes form the insulative coating known as myelin, which makes neural connections in the brain much faster and more streamlined. Without this insulation, what’s left is a long line of naked axons straining to send impulses along jagged, roundabout paths. That inefficiency, Kozai realized, doesn’t just cause a slowdown, but also means these neurons have to work much harder than their myelinated counterparts, wasting precious energy. “So oligodendrocytes are essentially energy savers,” he says. 

If Kozai’s hunch is correct about oligodendrocytes—an historically understudied cell in his research specialty—this work could have broad implications for a number of debilitating conditions.

Historically, the thinking has been that the trouble with the BCI starts like this: As a result of electrode implantation, blood vessels are damaged, which sends plasma proteins flying off where they shouldn’t be. Their presence on the wrong side of the blood-brain barrier unleashes an assault of immune cells, called microglia. And in that fallout, neurons die. 

But the team began observing that the friendly fire wasn’t the only problem; it was that these neurons, having been choked off from their blood supply, had simply starved to death. So Kozai wondered if they could somehow fortify the neurons against that starvation. “That’s what pointed us toward the oligodendrocytes.”

With this new R01 grant, Kozai is targeting certain progenitor cells that each have potential to give rise to either an oligodendrocyte or enemy number one: scar tissue. In a preliminary study, the team treated these cells with a drug to encourage the former. When administered before implant surgery, they found, the drug helped more neurons survive after the procedure. 

The project will also probe oligodendrocyte health more generally, insights that could potentially expand our understanding of traumatic brain injury and stroke—which both involve a decrease in blood flow in the brain—as well as multiple sclerosis (MS)—an autoimmune onslaught on neurons that’s initially sparked by oligodendrocyte death.

Kozai’s group may be one of the first to have suggested that preserving oligodendrocytes could be a novel treatment against dementia in Alzheimer’s. In that disease, the focus has long been on the plaques that form in the brain. 

“But there’s growing evidence that it’s actually the blood vessels that suffer first—the plaques form on the blood vessels before they form on the neurons,” Kozai explains. Amid the ensuing blood loss, it’s possible the neurons are more vulnerable, unable to maintain a clean environment, “and that, in turn, leads to the plaque forming on the neurons.”