image: Integrating regenerative medicine and brain-computer-interface concepts into a hypothetical 3D Neural Network in the sensory-motor loop for neurorestoration applications, with vascular integration to ensure self-sustainability.
Credit: Image/UC Irvine-USC
The National Science Foundation (NSF) will fund new research from the Keck School of Medicine of USC and the University of California, Irvine (UC Irvine) that seeks to revolutionize intelligent biocomputing and the treatment of neurological diseases. The four-year, $2 million grant is part of the Emerging Frontiers in Research and Innovation (EFRI) program, an initiative that funds cutting-edge science pushing the boundaries of human knowledge.
The premise of the USC-UC Irvine project is to combine two technologies that hold promise for treating brain injuries: regenerative medicine, which uses stem cells to repair damaged regions, and brain-computer interfaces (BCIs), which allow the brain to interact with and control external devices, such as robotic limbs. The team’s ultimate goal is to restore key brain functions—including movement, sight and speech—to patients who have brain damage from a stroke, spinal cord injury or other neurological problems.
“We’re exploring whether these lines of research, which have really been developing in silos before now, can be converged,” said Charles Liu, MD, PhD, a professor of clinical neurological surgery, urology and surgery at the Keck School of Medicine and director of the USC Neurorestoration Center. “This current award is the first that really merges two separate and previously independent concepts: regenerative medicine and brain-computer interfaces.”
Liu and his colleagues at UC Irvine have spent years developing BCIs for neurorestoration, and in 2017 received an $8 million grant from NSF to expand that work. Since then, they have received recognition from both NSF and the Engineering in Medicine and Biology Society of the Institute of Electrical and Electronics Engineers. Separately, Liu has also begun exploring how to use stem cells in human patients for neurorestoration.
“Our hope is that the whole might be greater than the sum of its parts—that combining these two concepts might be able to accomplish even more,” Liu said. “The EFRI program supports the creation of the science required before any application to treating human disease is possible. We think that when this science is developed, it’s going to be truly groundbreaking.”
Two technologies converge
On their own, both BCIs and stem cells hold promise for helping patients with brain and spinal cord damage, but each approach has its limitations. BCIs, which typically sense and stimulate brain activity through electrodes implanted in or on the brain, are limited by the capacity of the electrodes themselves. Stem cells injected into damaged brain regions have the potential to grow and learn, but scientists have not yet been able to create networks of neural stem cells that are both functional and self-sustaining.
The idea behind the new research is to use BCIs to support growth and learning in stem-cell networks by providing stimulation that mimics healthy brain activity. Liu, a neurosurgeon, will work directly with patients. His colleagues from UC Irvine, An Do, MD, lead principal investigator and an associate professor of neurology, Zoran Nenadic, DSc, a professor of biomedical engineering and Hung Cao, PhD, an associate professor of electrical engineering, will handle the project’s other components, including microelectronics engineering and neural signal processing. Leigh Turner, PhD, a professor of health, society and behavior at UC Irvine, will lead an exploration of the ethical, legal and social issues related to the project.
First, the team will develop a method of growing 3-D networks of neural stem cells in culture, which have been gathered from healthy patients and reprogrammed to an embryonic-like state. Cultured stem cells can form 2-D neural networks and small “organoids” that are limited in size due to an inadequate supply of nutrients. Liu and his colleagues plan to create artificial blood vessels that can help stem cell neural networks grow larger and thrive.
Next, the researchers aim to create a bidirectional connection between these cultured brain cells and the living human brain while patients perform a behavioral task. These studies will take place in epilepsy patients who have had electrodes implanted by the USC Epilepsy Care Consortium to manage their condition. The ultimate goal is to find out whether cultured cells can learn and grow in response to brain signals—for instance, while a person performs a motor task with their hands—then send signals back to the brain in return.
“If we create these 3-dimensional brain organoids but they still don’t respond to neural signals, then we’re back to where we started. We need to take these cultured neural networks and ‘hook them up’ to a human brain, much like we do with our BCI studies in the same human patients,” Liu said.
Eventually, epilepsy patients may benefit from this approach, because one standard treatment for epilepsy involves removing parts of the brain where seizures originate. Technology that can restore brain function could help mitigate neurological problems caused by such surgeries.
Intelligent biocomputing
Though this exploratory technology is still theoretical and many steps away from standard medical practice, Liu said if it is successful, it could ultimately help treat a broad range of conditions, including stroke, epilepsy, traumatic brain injury and congenital conditions that cause blindness and other problems.
If the researchers can produce 3-D neural networks that grow and learn, they plan to explore how powerful these intelligent biocomputers can become. Can they merely perform simple tasks, or are they capable of complex functions, such as logic and computing?
In the current project, Liu and his colleagues will also study and weigh the ethical implications of combining regenerative medicine with BCIs.
“We’re talking about creating, for the first time ever, a convergence of two technologies, both of which have very significant ethical facets,” Liu said. “Assuming this works out the way we propose, we want to make sure that the possibilities it creates are aligned with our ethics as a society.”
About this research
This work is supported by the National Science Foundation grant 2422412.
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