Electrical stimulation is helping Miami Project patients move again
By Josh Baxt
or most people, walking or lifting a coffee cup are simple acts they barely consider. But for those suffering from spinal cord or brain injuries, these simple tasks can be virtually impossible.
The Miami Project to Cure Paralysis, a Center of Excellence at the Miller School, is working to change that, and neuromodulation is one of its most innovative tools. The technique uses small electrical currents to stimulate nerves. By combining these stimuli with rehabilitation, Miami Project researchers at the Christine E. Lynn Rehabilitation Center believe they can help patients improve their abilities to walk and/or use their arms and hands.
“Neuromodulation seeks to activate the spinal cord or brain after injury to promote circuit restoration,” said W. Dalton Dietrich, Ph.D., scientific director of The Miami Project. “Quite often, even after severe injury, there are residual circuits that can be activated. We may not be able to restore full function, but we can hopefully help patients regain some function and improve their quality of life.”
The Miami Project recently received approval to conduct the first North American clinical trial for deep brain stimulation, which places electrodes inside the brain, to improve gait following a spinal cord injury. The team is also pursuing epidural stimulation, which puts electrodes on the spinal cord, and transcutaneous spinal cord stimulation (tSCS), which stimulates neural tissue through the skin.
The technology is promising, but there are still unanswered questions: What parts of the brain or spinal cord should be stimulated to improve specific functions? How much current should be applied and when? How should those signals be modulated so the central nervous system knows what they mean? Miami Project and neurological surgery researchers are combining expertise in neural engineering, neurosurgery, neurology, rehabilitation and other disciplines to answer these and other questions.
Breaking the Neuromuscular Code
An extension of the brainstem, the spinal cord orchestrates the circuits that carry messages throughout the body, sending rhythmic signals that control walking, breathing and other functions.
“When walking along, you activate your spinal cord pattern generator,” said Brian Noga, Ph.D., professor of neurological surgery. “At the same time, sensory signals are coming from your feet, legs and arms to update your brain on what’s happening in the real world. It’s an incredibly dynamic process.”
Essentially, Dr. Noga and colleagues are acting as codebreakers, trying to understand these brain signals and replicate them with electrodes that stimulate nerve cells. Breaking the code will help clinicians send signals the body understands.
“We want to find the electrical stimulation thresholds that initiate walking and continue it,” Dr. Noga said. “We have found that it’s not just a single pathway that produces walking. There is a command pathway and another, parallel, pathway. If we stimulate this other pathway, we can affect locomotion.”
W. Dalton Dietrich, Ph.D.
“Quite often, even after severe injury, there are residual circuits that can be activated.”
Miami Project
Brian Noga, Ph.D.
“We have found that it’s not just a single pathway that produces walking.”
Learning to Walk Again
A brain-computer interface (BCI) can detect a person’s intention to move by capturing signals recorded from the brain’s surface. After spinal cord injury (SCI), these motor commands are disrupted, preventing them from reaching the muscles. “Even after incomplete SCIs, where some nerve pathways remain intact, the ability to walk is often significantly impaired,” said Matija Milosevic, Ph.D., director of neuromotor rehabilitation at The Miami Project (shown above testing equipment with Ph.D. candidate Rizaldi Ahmad Fadli).
Dr. Milosevic, an assistant professor of neurological surgery and biomedical engineering, is working to develop therapeutic brain-controlled neuromodulation approaches for restoring voluntary function after incomplete SCI. His team has developed a non-invasive neuroprosthetic technology aimed at enhancing neuromuscular control in individuals with incomplete SCI. This approach involves pairing brain circuit activation with neuromodulation to improve walking. The approach has demonstrated the potential to restore walking abilities in patients many years after injury, even after discontinuing the stimulation.
“By providing the central nervous system with a ‘reward’ through enabling more efficient movements each time the BCI system detects an attempt to move, the body responds by forming new connections between the brain and the muscles that control walking,” Dr. Milosevic said.
His research team at The Miami Project and colleagues in biomedical engineering are now integrating artificial intelligence into their neuroprosthetic technology to enable more targeted activation of the central nervous system. This advancement aims to improve gait symmetry and further accelerate the therapeutic efficacy of brain-controlled neuromodulation, potentially enhancing recovery efficiency and reducing health care costs.
Matija Milosevic, Ph.D.
“The body responds by forming new connections between the brain and the muscles that control walking.”
Reengaging Arms and Hands
James Guest, M.D., Ph.D., professor of neurological surgery, and Leslie Morse D.O., chair and professor of physical medicine and rehabilitation, led the Miami Project’s and University of Minnesota’s collaborations in Up-LIFT. This multi-center study evaluated tSCS to improve upper extremity function in people with chronic spinal cord injuries.
While some neuromodulation efforts use implanted devices, tSCS is completely noninvasive, using electrodes on the skin to send current into the spinal cord. Up-LIFT combined neuromodulation with intensive arm and hand rehabilitation to stimulate neural circuits as they were being used.
“Typically, after spinal cord injury, these circuits don’t activate properly and remain below the electrical threshold,” Dr. Guest said. “We’re giving them that added push to become effective. Also, transcutaneous stimulation is easy to do, which means there’s a good chance it will enter practice.”
Results recently published in Nature Medicine showed tSCS, combined with rehabilitation, was both safe and effective, improving upper extremity function in many patients. In addition, Dr. Guest would like to use tSCS for other disorders. By testing different electrical frequencies, he hopes to find the right signal combinations to treat different conditions.
Stimulating the Vagus Nerve
Patrick Ganzer, Ph.D., an assistant professor at The Miami Project and the Department of Biomedical Engineering, is taking a slightly different approach. His group is implanting a small electrical device on the vagus nerve, the main contributor to the parasympathetic nervous system that controls the heart, digestion and other autonomic functions. When the vagus nerve is stimulated during rehabilitation, it can enhance the rewiring of damaged circuits.
“Our lab is focused on peripheral nerve stimulation to enhance the effects of rehabilitation and improve upper limb function,” Dr. Ganzer said.
Studies involving rehabilitation have patients interact with small devices they can manipulate with their hands or pull to measure forelimb strength. These objects contain embedded sensors that record their status to reveal the most efficient and timely stimulation required for precise vagus nerve stimulation during rehabilitation.
“Previous and ongoing studies use reactive vagus nerve stimulation triggered by good movements during rehabilitation, and signals can be recorded, such as force and angle, from the objects being manipulated,” Dr. Ganzer said. “It is possible to measure many signals, process them and use a smart algorithm to trigger optimal stimulation.”
Researchers stimulate the vagus nerve for around half a second, which releases neurotransmitters that promote neural circuit changes (neuroplasticity). But the stimulation must be paired with a good event, such as a patient handling an object in a specific way. Through this process, neuromodulation gives nerves special reinforcement to encourage nervous system change and increase the capacity for improved movement.
“Stimulating the vagus nerve releases molecules that provide reinforcement for facilitating learning and brain change,” Dr. Ganzer said. “We are trying to reinforce good brain activity during good movements and grow more brain connections back to paralyzed muscles.”
The Ganzer Kanumuri Neurotechnology Lab is now working with a quadriplegia model to better understand how vagus nerve stimulation can improve function. In addition, because the vagus nerve controls autonomic functions, this research could be applied to other conditions. Dr. Ganzer and Mark Nash, Ph.D., associate scientific director for research with The Miami Project and a professor of neurological surgery, are evaluating a noninvasive way to activate the vagus nerve to assess autonomic biomarkers and blood sugar regulation in chronic spinal cord injury patients.
“We may not think about it, but beyond muscles, there are many other events under brain control within a broad array of organs, and when these don’t work properly, there can then be an array of health issues,” Dr. Ganzer said. “We believe we can generate more brain connections with this therapy to enhance broader organ control as well.”
The Miami Project and colleagues worldwide have made great progress stimulating nerves to restore function, but there’s still work to be done. Dr. Dietrich envisions neuromodulation as one of many clinical strategies, including neuroprotection, cell-based therapies, axon regeneration and task-based rehabilitation, to help patients recover from brain and spinal cord injuries and neurodegenerative disorders. 
James Guest, M.D., Ph.D.
“Transcutaneous stimulation is easy to do, which means there’s a good chance it will enter practice.”
Miami Project
Patrick Ganzer, Ph.D.
“We believe we can generate more brain connections with this therapy to enhance broader organ control as well.”
