For two weeks straight, Nico U. Dosenbach, MD, PhD, sported a very pink — almost neon — fiberglass cast on his uninjured right arm for the sake of research. He wore the fingertip-to-upper-arm cast 24/7 during one of the hottest stretches of summer 2015 in St. Louis. Pink is his daughter’s favorite color and Maike, age 21⁄2, had never seen her father otherwise encumbered. He didn’t want to alarm her.
Dosenbach, who conducts research in the Neuroimaging Laboratory (NIL) at Mallinckrodt Institute of Radiology, endured the cast, the heat and the discomfort (it itched) to gain insight into the lives of his patients. Personal perspective aside, Dosenbach also wanted data — and lots of it — about how constraint-induced movement therapy (CIMT) impacts the brain.
Dosenbach, who also is a pediatric neurologist, spends about 20 percent of his time in the neurorehabilitation clinic at St. Louis Children’s Hospital and the remainder conducting research in the NIL.
Many of his young patients have hemiplegia — a type of cerebral palsy that causes paralysis on one side of the body — from strokes that occurred before, during, or shortly after their births. The brain injury can result in a wide range of physical, cognitive and behavioral effects, but is most often diagnosed as an infant becomes mobile and begins to favor one side of the body.
A common treatment for hemiplegia, CIMT (also known as forced-use therapy) immobilizes an individual’s dominant or “good” arm with a cast, forcing the impaired arm into action.
An “experimental” treatment
Although CIMT has been shown to improve upper extremity function children with hemiplegia, it’s considered experimental by insurers, who say there’s not enough evidence to support its use. Treatment also includes two or more hours of occupational therapy each weekday, with evening and weekend assignments. Typically, CIMT lasts two or three weeks, but is intense.
“It’s easier to get adults to do the therapy because you tell them: ‘This is important and you should use your other arm.’ It’s more difficult with little kids because they don’t want to do it. You have to make it essentially impossible for them to use their stronger, more dexterous hand or arm to obtain a therapeutic benefit,” says Dosenbach.
Re-firing the brain to rewire it
Dosenbach’s research interests include forced-use learning and use-driven functional network neuroplasticity, i.e., the brain’s ability to remap and/or create neural pathways. Repetition, as with all learning, helps the brain to develop new neural pathways. As one focuses on a particular task, the affected portion of the brain fires up and, over time, rewires itself. The more frequently pathways are used, the stronger they become. CIMT may help develop new network solutions for controlling the impaired limb.
Dosenbach wanted to gather enough data to measure changes in the brain associated with forced-use therapy. More specifically, he wanted a timeline that identified when neural and anatomic changes occurred within the brain. He discussed the idea with his colleague and Mallinckrodt research professor Abraham (Avi) Z. Snyder, MD, PhD, and graduate students Timothy O. Laumann and Adrian W. Gilmore.
“Going back and forth, we came up with this idea (of casting the dominant arm in a healthy adult),” says Dosenbach. “And then Avi said: ‘You should do this to your arm.’ And I replied: ‘You’re right, and I totally will!’”
One subject, more data
With Snyder, Dosenbach applied for and received a $10,000 facilities grant in scan time from Mallinckrodt Institute of Radiology for the pilot research project. The study’s clinical application was approved by Washington University School of Medicine’s institutional review board. Snyder is the principal investigator and Dosenbach is co-investigator.
“Normally we would study 20 to 30 people, but we were interested in seeing specific details in time and in anatomical space,” says Dosenbach. “If a study looks at an ‘average’ of people’s brains, you end up with a blurred vision of everything. I didn’t want that. Everyone’s brain is different anatomically.”
It took a year for Dosenbach to clear his schedule to accommodate the study. His goals were twofold. “On the basic science end, we wanted to capture a deep time course of network plasticity from this intervention in a single healthy person. On the clinical end, I wanted to gain some personal insight into what this therapy is like for the patient.”
62 brain scans later
In order to detect any alterations resulting from forced-used therapy, the research team that also included occupational therapist Catherine Hoyt-Drazen, OTD, postdoc Mario Ortega, PhD, and clinical research coordinator Annie Nguyen, MS, needed to first obtain baseline information on Dosenbach. He underwent a series of standardized motor performance tasks such as using a pegboard, moving blocks from one box to another, finger tapping, handwriting, and figure tracing, and his upper extremity movements were tracked using bilateral, wrist-worn accelerometers.
Dosenbach underwent daily fMRIs for two weeks before he was casted, two weeks while he wore the cast, and almost four weeks after the cast was removed. “I came in at 5:30 every morning,” he says, as scan time costs less in the pre-dawn hours, enabling the researchers to maximize their grant money.
He underwent a total of 62 brains scans, each lasting about an hour. As Dosenbach lay motionless on the MRI table, its computer was noisily acquiring hundreds of images of his brain. “It was like making a movie, with each day being a frame,” he says.
Dosenbach’s work schedule could not accommodate the amount of occupational therapy (OT) that his young patients receive as part of their treatment. He compensated the OT portion of forced-use therapy by doing all the work he routinely does every day with his less dominant and weaker arm — and what he does most is typing on his computer and writing notes by hand. But the young researcher, whose wife was then seven months pregnant and none too happy with his decision to immobilize his arm, also had responsibilities at home. “That was my therapy,” he says.
Although data from the pilot study has been collected, image processing and analyses is not yet complete. Dosenbach and Snyder intend to use that information to apply for a National Institutes of Health (NIH) grant that will allow them to gain an even greater understanding of use-driven functional network plasticity.
“I learned why the treatment might fail in kids,” says Dosenbach, who admits to “cheating” at least twice out of sheer frustration. “I also decided that the cast is overkill because it is too bulky, heavy and warm. The goal isn’t to make the patients itchy and not have their skin see sunlight; it’s to restrain them from using the dominant hand or arm. So we have to work on other, less obstructive ways to achieve the same results.
“For many tasks, forced-use therapy is not pure practice, like with a golf swing. You figure out new tricks, like how to open a jar. If you can’t open it one way, you might sit down and clamp the jar with your knees, then it’s easier. So it’s not all pure motor learning. It’s also finding new strategies for things you used to do with two hands, but now do with just one hand. And over time, you get better at it.”
Dosenbach’s main problem while he was casted was not going from his dominant right hand to his left hand, but rather going from two hands to one. The grip strength in his casted arm and hand decreased from124 pounds of force to 90 in just two weeks’ time.
“Across the board, my right arm/hand got worse immediately after it was casted, and began to improve after the cast was removed,” says Dosenbach. “My left hand got stronger with forced use, but not to the degree that my right hand got weaker.”
Although Dosenbach did experience what his patients undergo, it’s still not the same, he says. “The main difference is that my left hand is healthy. It’s way, way harder for my patients because they have decreased use of one arm/hand, and they’re much more frustrated. Forced-use therapy is much more taxing for them.
“The developing brain has great potential for plasticity,” says Dosenbach. “Once we understand it better and develop a better sense of how we can drive or optimize it, we can have better outcomes. That’s a realistic goal.”