When you grab a cup of coffee, you don’t think about it. The sensory neurons in your hand feel the pressure of the cup and alert your brain to stop contracting your muscles. If the cup starts to slip, sensory neurons detect it and alert your brain to contract your muscles again. For people whose sensory neurons have been damaged or cut altogether, this connection uniting touch, the brain and muscles is lost. And with it, the ability to properly grab that cup of joe.
People who have suffered nerve damage from injury, amputation or stroke have benefited greatly from improvements to prosthetic limbs and mechanical hands. Research also has shown that damaged nerves can regenerate with electrical stimulation. But the bigger picture of how to improve the lives of people with nerve damage has been missing. Until now.
A groundbreaking interdisciplinary research project is studying how nerves regenerate after injury and the best way to make it happen. With a $1.3 million grant from the National Institutes of Health, Erik Engeberg, Ph.D., associate professor in the Department of Ocean and Mechanical Engineering, has assembled a team to uncover the connections between the sense of touch and the capacity to manipulate a prosthetic device.
“As nerves regenerate, the amputee’s sense of touch evolves. As the sensation of touch improves with continued use and regeneration, the subject will gain improved control of [a robotic] hand. We’re looking at this synergistic interaction between motor control and evolving sensation of touch as nerve regeneration occurs, all simultaneously,” Engeberg said.
To study nerve regeneration, Engeberg and his colleagues have designed a “closed-loop” system that houses damaged nerve cells in fluid-filled chambers — this setup allows the team to study nerve regeneration in real time. The loop begins with a human subject, usually an amputee, who has been fitted with a sensor that measures electrical signals from muscles (this technique is called electromyography, or EMG).
When an amputee performs an action, such as grasping, electrical signals are sent to a robotic hand, impelling it to grasp. The robotic hand is equipped with sensors that mimic human touch. The touch sensations it “feels” are converted into electrical signals, which are then sent to the fluid-filled chambers to stimulate the damaged nerve cells. “The in vitro nerves are going to grow in response to the electrical stimulation, which is done in a way that’s biologically similar to the nerve impulses that travel in the peripheral nervous system,” explained Engeberg.
It is here, in the chambers, where the crux of the study lies. Each chamber contains an electrode and approximately 5,000 dorsal root ganglion cells (the type that send sensory information to the spinal cord). To simulate nerve damage, the investigators have cut away the cells’ axons, which are the long, slender threads that convey electrical impulses to other cells. The electrical signals from the robotic hand stimulate the neurons via the electrode. As the neurons regenerate in response to the stimulation, their axons grow down a specially designed microgroove that allows the researchers to better monitor and measure the process of regeneration.
“We have different frequencies feeding into the neurons, and we analyze the regeneration of those neurons to see whether those axons are going to grow back,” said Jianning Wei, Ph.D., associate professor of biomedical science in the Charles E. Schmidt College of Medicine. “My part is to see what kind of stimulation makes the peripheral neurons regenerate functionally and faster.”
To close the loop, the amputee manipulating the robotic hand will wear an armband that houses a microchip. “The chip accepts signals from the touch sensors connected to the prosthetic hand, allowing neuron regrowth after injury,” said Sarah Du, Ph.D., assistant professor in the Department of Ocean and Mechanical Engineering. “And the neuron regrowth signal, together with the EMG signals, will be used to improve the operation of the robotic hand.”
In that sense, explained Engeberg, the team is creating new mappings between the robotic fingertip forces and the microchip in the armband based on the way the nerves regenerate. “It’s pretty exciting,” he said.
The team includes a clinical perspective with collaborator Douglas Hutchinson, M.D., an orthopedic surgeon at the University of Utah, who has experience implanting neuroprosthetic electrodes in amputees. His expertise will be needed soon when the team starts working with amputees.
While an amputee operates the robotic hand, Emmanuelle Tognoli, Ph.D., associate research professor at the Center for Complex Systems and Brain Sciences, will use electroencephalography (EEG) to monitor the amputee’s somatosensory cortex, the area of the brain that processes information about pressure, vibrations and spatial patterning. This noninvasive technique will allow the team to safely and objectively quantify the amputee’s perception of touch.
The team is certainly not the first to study how electrical stimulation improves prosthetic use. Multiple researchers have collected these kind of data, frequently by implanting a chip in an amputee rather than using an external armband — a procedure that is not only costly and invasive, but also constrained, as data are limited to a single subject. What’s new about Engeberg’s approach is that it allows the team to work with multiple amputees and different robotic hands, stimulating thousands of nerves according to different types of movements, thus generating a lot of data in a short period of time.
“Receptors in hands that can sense are very complicated,” Tognoli said. “By studying the nerves in vitro, we can test richer ways to restore communication of tactile information. It’s a very fruitful way to test the interaction between plasticity at the neuron level, and perception, behavior and action of the whole person.”
The National Science Foundation initially funded the project in 2013. FAU’s Institute for Sensing and Embedded Network Systems Engineering added a seed grant. In October 2017, the NIH awarded the researchers a $1.3 million grant.
While the study’s application to neuroprosthetics is clear, the research is also relevant wherever damaged nerves can regenerate and form new connections: the high school gymnast who returns to competitions after recuperating from a spinal fracture, later landing a college scholarship. The paralyzed father taking his child to a sporting event will once again feel his child’s hand in his while ascending the bleachers.
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