October 17, 2016

UAB receives prestigious BRAIN Initiative grant for deep brain stimulation in Parkinson’s disease

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DBS surgery 2The University of Alabama at Birmingham has received a BRAIN Initiative grant of $7.3 million over five years from the National Institutes of Health to study new technology that could improve outcomes from deep brain stimulation, an increasingly important treatment for Parkinson’s disease and other movement disorders.

The White House BRAIN Initiative — Brain Research through Advancing Innovative Neurotechnologies — is a collaborative, public-private research initiative launched by the Obama administration in 2013.

UAB is an international leader in neuromodulation, which involves using electrical, chemical or magnetic stimulation to modulate the function of the human nervous system. Deep brain stimulation is a neuromodulation therapy that uses electrical current to improve slowness, muscle stiffness, tremor and other disabling symptoms of movement disorders.

The BRAIN Initiative award will enable UAB investigators to assess next-generation DBS technology made by Boston Scientific. Its new system can direct current in specific directions in the brain, which will allow a more tailored approach to DBS adjustments in individuals. This directional DBS approach has significant potential to enhance improvement and to minimize potential side effects from stimulation. 

“One of the difficulties in current DBS technology is that the electrical stimulus goes out in all directions, like a radio wave from a broadcast tower,” said Harrison Walker, M.D., associate professor in the Department of Neurology and the primary investigator of the study. “Based on previous studies in our laboratory, we believe that we can use this new electrode design to tailor the shape of the DBS electrical field in individuals and get better results with fewer side effects.”

To guide activation and adjustment of this complex new technology, the investigators will use recently identified biomarkers that measure brain rhythms triggered by DBS during surgery.  One major goal of the study is to test whether these brain rhythms can serve as a roadmap in individuals to arrive at optimal stimulator settings with the directional DBS device as rapidly as possible. 

After DBS surgery, patients will participate in a crossover study to compare outcomes with and without directional stimulation. This study design takes advantage of the ability to instantly change stimulator settings in an individual. At the end of the crossover study, investigators will carefully measure motor, cognitive and behavioral outcomes. Importantly, participants will be able to express which treatment strategy they preferred, based on changes in symptoms and quality-of-life measures that are most important to them.

UAB has performed more than 1,000 DBS and other stereotactic functional neurosurgery procedures for movement disorders including Parkinson’s disease. To refine targeting during the DBS procedure, neurologists and neurosurgeons perform brain mapping and measure the response to stimulation during surgery. The goal is to maximize potential benefits and minimize potential side effects during device activation a few weeks later in the neurology clinic. 

“One of the difficulties in current DBS technology is that the electrical stimulus goes out in all directions, like a radio wave from a broadcast tower. Based on previous studies in our laboratory, we believe that we can use this new electrode design to tailor the shape of the DBS electrical field in individuals and get better results with fewer side effects.”

Walker’s previous research has identified biomarkers with significant potential to guide targeting and activation of the DBS device in patients with Parkinson’s disease. Biomarkers are measurable signs that can be used to diagnose or treat disease. In this case, the UAB team is studying whether specific patterns of cortical activation triggered by the DBS pulse can predict the best combination of DBS contacts used for clinical therapy. These cortical activation patterns are measured with electrodes on the scalp (electroencephalography) and on the surface of the brain (electrocorticography). This study will investigate the potential value of these biomarkers for refining positioning of the DBS electrode during surgery and for improving the time-consuming, trial-and-error process of stimulator adjustments in clinic.

“There has always been a trade-off in deep brain stimulation, balancing the positive effects against the risk of unwanted side effects,” said co-investigator Barton Guthrie, M.D., professor in the Department of Neurosurgery at UAB. “It’s a challenging undertaking to determine the best placement of the lead, and to establish the appropriate contacts for activation and other stimulation parameters. Our hope is that, with the greater flexibility afforded by the new technology, coupled with the discoveries Dr. Walker has made in tracking biomarkers for effectiveness, we’ll be able to produce even better results for patients.”   

“Advances in DBS technology such as emerging directional lead designs, are outpacing our clinical and scientific knowledge of how DBS actually works,” Walker said. “In addition to rigorously evaluating directional stimulation, this trial should allow us to identify physiological measures that could eventually be used to adjust DBS settings in real time based on the needs of the patient in daily life. Additionally, this work could serve as a foundation to guide neuromodulation strategies for other movement disorders and for emerging indications such as epilepsy, obsessive compulsive disorder, major depression and other disorders.”

“There is no better work being done in neuromodulation than that at UAB, and this NIH BRAIN Initiative grant confirms the respect UAB enjoys in this field,” said UAB President Ray L. Watts, M.D., a practicing neurologist and expert in Parkinson’s disease. “This important research is made possible due to the strong collaboration between the Departments of Neurology and Neurosurgery, coupled with the multidisciplinary contributions from engineering, physical therapy, radiology, otolaryngology and biostatistics. This research will continue to showcase UAB’s important contributions in movement disorders, and could provide significant improvement in the quality of life for thousands of people with Parkinson’s disease.”

The scientific steering group for the BRAIN Initiative grant includes Walker and Guthrie, along with Arie Nakhmani, Ph.D., assistant professor of electrical and computer engineering; Gary Cutter, Ph.D., professor of biostatistics; Christopher Hurt, Ph.D., assistant professor of physical therapy; Daniel Phillips, Ed.D., instructor of otolaryngology; Roy Martin, Ph.D., associate professor of neurology; and Mark Bolding, Ph.D., assistant professor of radiology.