Rewiring the brain to improve rehabilitation outcomes

Scott Frey, PhD, was just a young child when he first began to think about how science and rehabilitation melded together.

“My mother had multiple sclerosis and I grew up going to therapy and neurology appointments with her,” he says. “That sparked an interest in science and biology and, ultimately (as Frey moved through college and graduate schools), to my current focus in cognitive neuroscience and neuro-rehabilitation. I wanted to see if there was some way, without a clinical background, that I could have an impact on the quality of care.”

His impact has become far-reaching. Frey conducts research that both informs and guides clinicians toward the development of better rehabilitative care practices for patients diagnosed with diseases or injuries to the brain, spinal cord or peripheral nerves. He has searched for these evidence-based rehabilitation strategies for more than two decades, with remarkable success. This summer, he joined the Program in Occupational Therapy, establishing the Rehabilitation Neuroscience Laboratory and bringing with him his team of researchers and post-graduate students focused on pushing rehabilitative science breakthroughs into clinical practice.

Carolyn M. Baum, PhD, OTR, FAOTA, the Elias Michael Executive Director of the Program in Occupational Therapy, enticed Frey to Washington University. “Dr. Frey’s lab has been asking the questions that are important in understanding rehabilitation approaches for years,” she says. “Our profession’s first major paper, ‘The Philosophy of Occupation Therapy,’ was written by a neurobiologist (Adolf Meyer, MD) who told us it is the use we make of our bodies that influences our every organ. That statement has always prompted the questions of ‘why’ and ‘how’ that we ask in the profession. If we as OTs understand the relationship between brain behavior, performance and participation, we will give more understanding to the rehabilitation sciences and to those trying to understand how the brain works.”

Early hints at the plasticity of the brain to rewire itself and the potential impact of neuro-rehabilitative techniques came in the 1980s, when researchers began to find evidence that a mature brain could restore some loss of function in patients recovering from stroke or epilepsy. Frey, who was awarded one of the first cognitive rehabilitation grants from the James S. McDonnell Foundation while at Dartmouth College, initially worked with patients who had intractable epilepsy. He studied how the brain rearranged signaling and function following split-brain surgical procedures in which the brain’s two hemispheres are separated so that seizure activity doesn’t “jump” from one side of the brain to the other. He then turned his attention to individuals who had experienced strokes or amputations.

“One of our recent aha moments came when we discovered during brain imaging studies that areas of the brain devoted to a hand that was lost through amputation start to respond to the other remaining hand,” Frey says. “In other words, we found that areas of the brain that were previously used for motor and sensory functions of the amputated hand had actually re-targeted their functions to help compensate for the brain loss on the non-dominant side. That is tremendously important because we see evidence for similar plasticity and brain reorganization in patients with stroke who have damage on one side of the brain.”

Amazingly, not only can the brain rewire itself, it seems it can continue to do so long after an injury has occurred. In previous research, Frey and his colleagues evaluated a 54-year-old man who had lost his hand 35 years prior and then underwent a hand transplant. Functional MRI studies found that with targeted rehabilitation, the man’s brain reorganized its own sensory signaling pathways to adapt to the transplanted hand.

“One of the key ideas in neuro-rehabilitation is that the brain can adapt to stimulation and reorganize itself to restore function,” he explains. “Our research found that this rewiring of the brain can occur even years after a traumatic injury, which points to the critical impact that neuro-rehabilitation can have on both early and long-term outcomes.”

His research has peaked the interest of the U.S. Department of Defense (DoD) due to the rising number of war-related injuries and amputations. In addition to a large grant from the National Institutes of Health (NIH), Frey was awarded two grants from the DoD and the U.S. Army to further examine the role of cortical plasticity in patients with hand amputations.“It’s like looking at the inner workings of a clock.” Frey says of his translational research projects. “We need to understand the gears, springs, and how it winds. It’s the same with the brain. We can take advantage of how the brain reprocesses information and changes signaling to improve how we develop rehabilitative approaches.”

Frey now is taking his earlier findings and applying them to patients with peripheral nerve injuries. He is planning collaborations with Susan Mackinnon, MD, chief of Division of Plastic and Reconstructive Surgery, and her team, who specialize in nerve transplantation. Recently, Mackinnon performed the world’s first donor nerve transplant.

“Many of their patients have severed nerves of the forearm or hand, which cuts off the nerve signaling to the brain,” says Frey. “When the severed nerves are repaired or when there are donor nerves, can we take the techniques that target plasticity in the brain (such as neurostimulation) and facilitate recovery in these peripheral nerve injury patients, too? I think we can.”

The confluence of neuroscience and rehabilitation on the campus is what drew Frey to the Program in Occupational Therapy and to Washington University. In addition to his leadership of the Rehabilitation Neuroscience Laboratory, Frey also chairs the Program’s new Rehabilitation and Participation Sciences (RAPS) PhD degree program. His goal is to offer interdisciplinary training opportunities and develop a new generation of scientists capable of driving innovation in the field of rehabilitation through evidence-based research.

Nathan Baune is one of the PhD students who followed Frey from the University of Missouri-Columbia to Washington University to work in the Rehabilitation Neuroscience Laboratory. As part of his role, Baune is trying to pinpoint the brain mechanisms involved in controlling hand functions during fine motor skills. “The advantage of being at Washington University is that we can work closely with physicians, rehabilitation specialists and occupational therapists,” he says. “We also are working with imaging specialists at Mallinckrodt Institute of Radiology who are pioneers in neuroimaging techniques. It’s that integration of resources and expertise that will enable us not only to advance our research agenda, but also to more rapidly translate our findings into clinical practice.”

Adds Frey, “In watching how my mother was cared for before she passed away, I realized that the important thing was not doing something based solely upon intuition, but on actual evidence, on finding out the ‘why’ and then the ‘how’ behind effective rehabilitation strategies,” he says. “If we can continue to identify better neuro-rehabilitative practices, we can influence and improve the quality of life for many, many patients in the years to come.”

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