For 50-70 percent of patients in the advanced stages of Parkinson’s disease (PD), Deep Brain Stimulation (DBS) can seem like a miracle. DBS is a surgical treatment in which electrodes that emit electronic impulses are implanted deep into the brain. The moment the device is switched “on”, PD’s characteristic movement disorders - including tremor, muscle rigidity, and slowed movement - vastly diminish. What’s more, patients who have undergone DBS slash intake of therapeutic medications by an average of 50 percent, decreasing unpleasant side effects such as uncontrolled bodily movement.
Despite the successes of DBS, it is far from the perfect solution. Following treatment, patients experience new difficulties, such as a reduced ability to learn new tasks, called procedural learning. Alan “Chuck” Dorval, Ph.D., Brain Institute USTAR investigator and assistant professor of bioengineering, University of Utah, attributes such adverse effects to the fact that scientists understand very little about how, or why, DBS works.
“Originally, DBS was the outcome of a serendipitous discovery,” he explained. “In order to treat this disease more efficiently, we need to understand the ways brains in disease and healthy states process information differently. That’s my job.”
USTAR recruited Dorval to its biomedical device innovation team in June 2009, largely based on his work with DBS conducted while a postdoctoral researcher at the University of North Carolina.
Dorval has been instrumental in expanding the institute’s expertise in the area of neural interfaces - the design of devices that improve central nervous system functions in impaired individuals. “One of the major goals of the Brain Institute is to partner with colleagues at the U, a world leader in the area of neural interfaces, to build next-generation technologies,” said John White, Ph.D., executive director of the Brain Institute. “Hiring Chuck Dorval was a big step toward this goal. He gives us increased strength in rational device design, computational methods, and animal models of human motor disorders.”
Dorval is uncovering the mysteries of how the parkinsonian brain works by examining brain activity in rats with PD-like symptoms. He has found that neurons in the parkinsonian basal ganglia - a region that signals to motor circuitry in the brain - fire neural signals more rapidly and less rhythmically than healthy ones. When the diseased rats are treated with DBS, the neurons fire even faster, and extremely rhythmically. These findings suggest that just as a crew relies on a coxswain’s rhythmic chants to row smoothly, the brain’s motor circuitry depends upon regular signaling from the basal ganglia to drive efficient body movement.
His research also explains why DBS treatment makes it difficult to learn new tasks. A coxswain who focuses his efforts on counting loudly and persistently will have trouble performing other duties simultaneously. Similarly, when DBS-treated basal ganglia continually issue rapid, strong commands to motor circuitry, they are less able to perform other functions, like facilitating procedural learning. “Any other information that the basal ganglia are trying to process can’t get through. It is being drowned out,” said Dorval.
Dorval is now using what he has learned about how PD and DBS affect information processing to design improved and novel types of DBS. He is determining whether by changing where DBS is positioned in the brain, and by altering DBS electrical patterns, he can reduce PD motor symptoms without creating adverse side effects. “It’s conceivable to come up with a type of stimulation that treats the motor symptoms but also allows the basal ganglia to process other information,” he explained.
He is also taking a second approach toward remedying the problems with DBS: paradoxically, by investigating how the healthy brain processes information. He is tracing how signals travel from the basal ganglia to re-wire neural connections in the healthy brain, thereby creating new memories that are essential for tasks like procedural learning. He will then determine whether he can modulate DBS to induce specific basal ganglia firing patterns that can reinforce those connections and enhance the ability to learn. “If we could modify DBS to enhance information transmission, persons with PD might retain or even regain motor learning skills,” he explained. “This would allow them to learn motor strategies to compensate for, or even unlearn, motor symptoms.”
As an undergraduate majoring in engineering and computer science, Dorval never could have predicted that he would have a career researching human disease therapies. However, it was not long before he switched to, and stuck with, bioengineering, drawn to its potential to help others. “I think it’s worth focusing on those unresolved problems that are likely to impact humanity in the near future,” he said.
This sentiment remains a central tenant of his work today. “The Brain Institute provides me daily interactions with superb neuroscientists necessary for basic neuroscience discoveries. USTAR provides me the infrastructure required to deliver the fruits of those discoveries to improve the lives of persons with neurological disorders,” remarked Dorval. “I am extremely fortunate to have found an academic home so focused on both aspects of neuroscience translation: discovery and delivery.”
The Utah Science Technology and Research initiative (USTAR) is a long-term, state-funded investment to strengthen Utah's "knowledge economy” and generate high-paying jobs. Funded in March 2006 by the State Legislature, USTAR is based on three program areas. The first area involves funding for strategic investments at the University of Utah and Utah State University to recruit world-class researchers. The second area is to build state-of-the-art interdisciplinary facilities at these institutions for the innovation teams. The third program area involves teams that work with companies and entrepreneurs across the State to promote science, innovation, and commercialization activities. For more information, go to www.innovationutah.com or follow http://twitter.com/Innovationutah.