In a groundbreaking study, a collaborative team of physicians, neuroscientists, and engineers at Duke University has unveiled two innovative strategies utilizing deep brain stimulation (DBS) to enhance the treatment of Parkinson’s disease. The research, published in the journal Brain, introduces simultaneous targeting of two crucial brain structures, coupled with a novel self-adjusting device. This dual approach proved effective in efficiently addressing and improving the disruptive symptoms associated with the movement disorder.
Deep brain stimulation has been a prescribed therapy for the symptoms of advanced Parkinson’s disease for the past two decades, especially when medication alone becomes insufficient. The technique involves employing a device akin to a pacemaker to deliver electrical impulses to specific areas within the brain. This targeted stimulation has demonstrated the ability to alleviate tremors, stiffness, and involuntary, writhing movements that may develop after years of medication.
While DBS has proven effective in addressing these symptoms, it has its limitations, prompting ongoing exploration by physicians and researchers for ways to enhance its efficacy. Senior author Dennis Turner, a professor of neurosurgery, neurobiology, and biomedical engineering at the Duke University School of Medicine, explained that electrodes for DBS are typically placed in either the subthalamic nucleus or the globus pallidus, two brain structures closely associated with movement. Each location offers benefits depending on the patient’s symptoms, but the team believed that placing electrodes at both locations could complement each other, potentially reducing medication doses and side effects.
Beyond expanding the area of stimulation, the researchers sought to investigate whether adaptive DBS could optimize their system. In traditional DBS, physicians set key electrical parameters, such as amplitude, pulse frequency, and pulse duration, to treat symptoms while minimizing side effects. However, these parameters often remain unchanged for extended periods, leading to suboptimal outcomes.
Warren Grill, the Edmund T. Pratt, Jr. School Distinguished Professor of Biomedical Engineering at Duke, emphasized the need for adaptability in stimulation levels, stating that a patient’s requirements change based on factors like medication or activity levels. He likened an adaptive system to a smart thermostat that adjusts based on external conditions.
To implement this tailored approach, the team collaborated with Medtronic, a medical device company, using experimental technology to create adaptive DBS techniques. The device was programmed to sense and record key biomarkers and brain activity, allowing for automatic adjustment of stimulation parameters throughout the day to provide optimal symptom relief.
The team conducted a clinical trial at Duke University Medical Center involving six patients between 55 and 65 years old, each presenting varying symptoms of Parkinson’s disease. The researchers initially spent two years evaluating the efficacy of stimulating both the subthalamic nucleus and the globus pallidus with standard continuous DBS. The results, measured through patient feedback, tracking movement without involuntary actions, and medication reduction without symptom recurrence, guided the subsequent experiments to establish parameters for an adaptive DBS system.
During this phase, the team focused on beta oscillations, a specific frequency of brain activity in the subthalamic nucleus associated with the slow, halting movement observed in Parkinson’s cases. Testing different levels of stimulation helped determine optimal beta oscillation levels for symptom improvement under various circumstances.
After two years of study with the adaptive system, the team found that targeting both the subthalamic nucleus and the globus pallidus simultaneously improved motor symptoms more effectively than targeting either region alone. Additionally, the adaptive DBS applied less stimulation but was equally effective as dual-target continuous DBS in both clinical and home settings.
According to Kyle Mitchell, Assistant Professor of Neurology at Duke University School of Medicine, the patients are experiencing exceptional clinical responses to dual-target stimulation. The adaptive DBS tool has shown promise in providing a tailored and elegant therapy, matching clinical responses while minimizing stimulation. Encouraged by these positive outcomes, the team plans to further optimize adaptive deep brain stimulation and pursue additional testing in the next stage of clinical trials.
Warren Grill expressed gratitude to the participants, their families, and caregivers for their significant contribution to the experimental work, emphasizing the promising potential of this research in advancing the field of deep brain stimulation for Parkinson’s disease.
Journal Reference
Stephen L Schmidt et al, At home adaptive dual target deep brain stimulation in Parkinson disease with proportional control, Brain (2023). DOI: 10.1093/brain/awad429.
