By Beth Miller, Engineering Momentum
The human brain is one of the most powerful structures known to man.
Not only is it important to health and disease, but also to learning, creativity and imagination, psychology, business and the arts. The brain makes life happen, and that’s why the world’s leading researchers are focusing more intently on unlocking its mysteries.
This research is so important that President Barack Obama earmarked $100 million in the Fiscal Year 2014 budget for the BRAIN (Brain Research Through Advancing Innovative Neurotechnologies) Initiative to help scientists and engineers find new ways to treat, cure and prevent brain disorders and injuries. In addition, the National Academy of Engineers has designated the reverse engineering of the brain as one of its Grand Challenges awaiting engineering solutions, and the European Brain Council declared 2014 the Year of the Brain.
Learning how the brain works has the potential to improve life, from restoring function to someone disabled by stroke or spinal cord injury to making Internet searches faster and more accurate. And this research is not limited to the School of Medicine. Many of these researchers are conducting pioneering work in medicine and health at Washington University in St. Louis’ School of Engineering & Applied Science in mechanical and electrical engineering, biomedical engineering, computer science and computational biology.
The brain-computer interface
When Dan Moran, PhD, was growing up, he watched “The Six Million Dollar Man” and “The Bionic Woman,” television shows that featured fictional characters injured in accidents, then given “bionic” surgical implants that gave them superhuman abilities they used to fight injustice. As a high school baseball player, Moran watched his friend slide into home plate headfirst and break his neck. This incident motivated Moran, now associate professor of biomedical engineering, to study electrical and biomedical engineering to find better ways to restore function for patients with spinal cord injuries such as his friend.
Moran works with Eric Leuthardt, MD, associate professor of neurological surgery and neurobiology at the School of Medicine and of biomedical engineering and mechanical engineering & materials science at the School of Engineering & Applied Science and director of the Center for Innovation in Neuroscience and Technology, who joined the project as a neurosurgery resident, and now works with humans who have electrodes placed on the brain’s surface; and Kilian Weinberger, PhD, assistant professor of computer science & engineering. The team uses an interdisciplinary approach to restoring function to these patients by using a brain-computer interface, a communication method between the brain and an external device. The team has a $2 million grant from the National Science Foundation to create brain-machine interface technology that allows direct control of external devices as if they were a natural extension of the body.
“Engineering takes us from a research model to understanding an application that would otherwise not be possible."
— Eric Leuthardt, MD
Moran has spent several years working with an animal model of a brain-computer interface, in which subjects learn to control images on a screen simply by thinking about moving them. The method has the potential to allow patients with spinal cord injury and without use of a limb to move the limb with their thoughts.
By implanting a 2-centimeter chip as thin as plastic wrap in the brain, Moran and his team can record brain activity to make sophisticated computer models.
“Normally, one side of the brain controls one hand, and the other side controls the other hand,” Moran says. “When someone has a stroke, he or she is affected on one side. With our special co-adaptive algorithm and decoding, we’re not limited to that, so we can have both hemispheres control both sides.”
Weinberger takes the data from the brain recordings and designs the algorithms that allow the movement to take place.
“When a person moves his hand to the right, the data in the brain recordings shows that,” Weinberger says. “If you give that information to the algorithm, eventually it starts picking up the patterns in the data and making predictions. Then the patient can just think about moving the hand, and the robotic hand will move.”
While this may sound like science fiction, it’s the perfect confluence of engineering and medicine.
“In the next five years, I see clinically approved brain-computer interfaces and consumer brain-computer interfaces that will be more widely used and applied,” Leuthardt says.
The mechanics behind it
WUSTL engineers study the brain’s various mechanical properties, such as shape, strength, flexibility, how it handles force and in what direction physical waves travel. Philip Bayly, PhD, chair of the Department of Mechanical Engineering & Materials Science and the Lilyan and E. Lisle Hughes Professor of Mechanical Engineering, collaborates with others in Engineering and Medicine to take a closer look at the brain from a mechanical perspective.
Earlier this year, Bayly received a five-year, $2.25 million grant to better understand traumatic brain injuries in efforts to improve methods for prevention and treatment. The grant will allow Bayly and his research team to develop 3-D computer models of brain biomechanics that will give researchers and clinicians a better understanding about what happens to the brain during traumatic brain injury.
“It’s really hard to simulate the brain because it’s very complicated. The necessary ingredients for good simulations are the material properties, the structure (how the materials are put together) and data for validation. That’s what we’re providing,” Bayly says.
“The world is going to learn about the basic physics of brain injury, and also develop approaches to prevention and therapy, through computer simulation.”
— Philip Bayly, PhD
The National Science Foundation also funds Bayly’s work, including a project with Joel Garbow, PhD, research associate professor of radiology at the School of Medicine, using non-invasive magnetic resonance elastrography (MRE) to view and measure different properties of waves when they travel in different directions in the fibrous materials of the brain. What they determine could ultimately lead to new diagnostic tools for nerve and brain disorders and new insight into how artificial tissue degrades over time.
Larry Taber, PhD, the Dennis and Barbara Kessler Professor of Biomedical Engineering, collaborates with Bayly to study the shape of the brain using a combination of computational modeling and experiments. But instead of looking at the mature brain through imaging, Taber starts at the very beginning by looking at how the brain develops its shape.
Taber, an aerospace engineer by training, studies how the neural tube, the embryo’s precursor to the central nervous system, which includes the brain and spinal cord, takes its shape using chicken embryos as a model. The way the chicken brain forms in its first few days is very similar to humans in the first trimester of development, Taber says.
“The embryo undergoes dramatic changes in geometry through the stretching and bending of tissues,” Taber says. “The brain, the heart and other organs are created by tissues growing and being deformed by mechanical forces.”
Supported by a five-year $1.6 million grant from the National Institutes of Health, Taber studies how organs develop in the embryo, how they acquire their characteristic shapes, what happens when things go wrong and how the tissues adapt to distress.
“We look at how embryonic tissue responds to changes in the mechanical environment,” he says. “There are certain responses that most embryonic tissues have. We found a similar response in the heart and brain to changes in loads, and we think there may be some fundamental principle there.”
Listening well
People who wear hearing aids often complain about background noise interfering with their ability to hear, particularly in loud environments such as restaurants. As a result, people may stop wearing hearing aids or stop going out altogether.
Dennis Barbour, MD, PhD, associate professor of biomedical engineering, has an idea that may help people learn to overcome the background noise — playing specially designed video games.
Barbour and Nancy Tye Murray, PhD, professor of otolaryngology and of audiology and communication sciences at the School of Medicine, recently received a grant from the University Research Strategic Alliance to create video games designed to help with listening training. The therapy is part of a field called cognitive neurotherapeutics, in which the therapy targets the brain’s neuroplasticity, or the ability for the nerve cells in the brain to compensate for injury and disease. Under the right circumstances, these nerve cells can adjust their activities in response to new situations or to changes in their environment.
“Our strategy is to develop games that are fun enough that people want to explore them,” Barbour says.
Blending neural engineering, cognitive neurotherapeutics and software design, the project reaches into cognitive, computational, rehabilitation and auditory fields.
“We don’t know how much the deficit in listening takes place in the brain compared to the ear,” Barbour says. “We do know that about 30 million people in the United States have hearing loss, while close to 70 million have a listening disability. It’s possible that listening is a skill that could be taught better with the right intervention.”
Barbour says they think the video games will be more effective than traditional listening training, in which users hear the same words over and over.
“We train you to get better at listening by requiring you to listen to the dialogue to advance in the game and by giving strategies on how to listen well.”
— Dennis Barbour, MD, PhD
The team has three games in development. One involves running in exotic locales around the world. The runner runs faster if he or she performs better in listening to the target words. Another game makes the player a detective to solve a crime and involves interviews with suspects and witnesses. The third game involves having to talk to people at a cocktail party and pick up target words.
The video games will allow users to make choices as they go through the game. Based on the outcome, Barbour and Tye-Murray will track how well they do, which may uncover new principles of auditory training that researchers haven’t yet discovered.
The biological systems approach
Alzheimer’s disease is a tragic, progressive disease in which memory loss, confusion, disorientation, mood and behavior changes progressively get worse over time. It is the sixth leading cause of death in the United States. Parkinson’s disease involves shaking or tremor, stiffness in the limbs, slow movements and balance and posture issues and is the 14th leading cause of death in the United States. And Huntington’s disease is a genetically inherited neurodegenerative disorder that has many of the neuropathological features of Alzheimer’s and Parkinson’s disease.
Engineers at Washington University are looking at the connections between these three devastating neurodegenerative diseases using interdisciplinary approaches that involve collaborations between researchers within Engineering and clinical scientists at the School of Medicine. The Center for Biological Systems Engineering (CBSE) is an important catalyst for these collaborations. Research within the center focuses on modeling, predicting and designing functions of biological systems that result from integration of signals and responses of biomolecular and cellular networks.
Rohit Pappu, PhD, professor of biomedical engineering and director of the CBSE, delves into the biophysics and engineering of intrinsically disordered proteins, or proteins that lack a well-defined structure. These proteins often aggregate, or clump, leading to the death and disease of neurons, as in Alzheimer’s disease.
His research has yielded important insights regarding the molecular basis of Huntington’s disease. Pappu and his team are working to understand the connection between genetic mutations in the protein huntingtin and cellular consequences of huntingtin aggregation. This work, funded by the National Institutes of Health, has highlighted the importance of sequence and cellular contexts as modulators of huntingtin aggregation. These insights result from a combination of state-of-the-art computational modeling and experiment methods that are used by Pappu and his team. Recently, Pappu and his team have started to leverage their expertise to understand how networks of interactions with other abundant proteins in cellular contexts help modulate the properties of proteins involved in forming plaques seen in Alzheimer’s disease. This is an area of growing synergy between Pappu and Jan Bieschke, PhD, assistant professor of biomedical engineering and a member of the CBSE.
In neurodegenerative diseases, a protein changes shape from a functional folded form into a different fold in the polypeptide chain, taking on an amyloid structure in which multiple copies of the same protein assemble into strong and stable fibers. But the process of making the fibers is very toxic to the cells, Bieschke says.
“In a brain with Alzheimer’s disease, there are big clumps of plaque made up of these fibril protein structures,” Bieschke says. “The challenge from the mechanistic perspective is understanding how that fibril formation process works, why it is toxic for the cells and what can be done about it, since there is no cure or treatment to slow the disease process.”
“Our overall mission is to bring quantitative tools to studying this process in vivo, in cells and, in the end, in the organism.”
— Jan Bieschke, PhD
Bieschke is looking for proof-of-principle experiments for new therapeutic strategies. So far, he’s found two that derail the amyloid formation process, including one involving an antioxidant substance in green tea.
Given the strong collaborative effort at Washington University, progress in these areas is likely to happen, Bieschke says.
“You have this strong Alzheimer’s disease clinical focus and you have the biophysics, biomedical engineering and the CBSE that try to vertically integrate computational basic modeling, analysis and experimental studies. This is a very productive and collaborative environment,” Bieschke says.
The CINT, an interdisciplinary group based in the Department of Neurosurgery at the School of Medicine, has brought together leaders from the fields of medicine, engineering, law and business in an effort to remove classic barriers between these fields to allow a more open exchange of ideas and insights.
Led by Eric Leuthardt, MD, director of the CINT, nearly half of the center’s faculty are from the School of Engineering & Applied Science.
Faculty in the CINT work to generate new ideas, study and validate them and translate them into technology that will help patients with neurologic disease, stroke, traumatic brain injury or spinal cord injury. Their research includes neuroprosthetics, motor and speech physiology, stroke rehabilitation and epilepsy, as well as clinical work with brain mapping and inoperable brain tumors.
Ultimately, the technologies that are born from the CINT will help solve medical problems with no current solution.