Bucknell Study Optimizes Deep Brain Stimulation for Parkinson’s Disease

A new study led by Bucknell University Professor Karlo Malaga, biomedical engineering, has identified key insights into optimizing deep brain stimulation (DBS) for Parkinson's disease patients. Published in the March 21 edition of the Journal of Neurosurgery, the research pinpoints specific areas in the subthalamic nucleus (STN) where DBS can alleviate symptoms like gait disturbances (deviations from normal walking).

DBS is a surgical treatment option for Parkinson's patients who no longer benefit from traditional medications such as levodopa, which over time can cause side effects like dyskinesia — involuntary movements. The procedure involves implanting electrodes in the brain to deliver electrical pulses that modulate abnormal neural activity in targeted regions. While effective, DBS outcomes vary depending on where stimulation occurs.

"DBS is typically for patients who have exhausted all other treatment options," Malaga says. "It isn't a first-line treatment, but for some, it offers significant relief from debilitating motor symptoms."

Malaga's research team, which included Jackie Zak '24 and collaborators from the University of Michigan, analyzed data from 40 Parkinson's patients with DBS implants in the STN. Using MRI and CT imaging, the researchers created 3D electric field models for each patient, enabling them to visualize how DBS affected specific regions of the STN. This approach revealed that stimulation targeting the anterior STN significantly improved gait-related symptoms, such as freezing of gait (FoG).

"Our study found that more anterior stimulation within the STN correlated with better outcomes for gait disturbances," says Malaga. "This was based on our tissue activation analysis with gait scores from the Movement Disorder Society’s Unified Parkinson's Disease Rating Scale."

Notably, patients with more anterior STN activation showed greater improvement in FoG and overall gait scores compared to those with more posterior activation. However, anterior targeting also carries risks, as previous research has linked it to potential side effects, such as worse neuropsychological outcomes in patients with a history of depression.

The new findings build on earlier studies indicating that DBS outcomes depend on precise stimulation location. The research suggests that side effects often arise from unintended stimulation of nearby structures, highlighting the need for accurate targeting.

"The relationship between stimulation location and clinical outcomes is complex," Malaga says. "Our study emphasizes the importance of patient-specific models to optimize DBS for each individual's symptoms while minimizing side effects."

Using data-driven computational modeling, the researchers demonstrated that stimulation spread — influenced by factors like stimulation amplitude and tissue conductivity — can be individually modeled through the volume of tissue activation models. Unlike traditional electrode-based analyses, which focus solely on electrode position, the volume of tissue activation models accounts for stimulation spread in all directions from the electrode and its impact on adjacent brain regions.

The study's findings have significant implications for clinicians seeking to refine DBS therapies. By identifying symptom-specific "sweet spots" within and around the STN, clinicians can personalize DBS settings to address individual needs. For instance, anterior stimulation may benefit patients with gait disturbances, but caution is needed to avoid exacerbating other symptoms or cognitive impairments.

The study underscores the importance of tailoring DBS therapy to each patient's unique symptom profile. Parkinson's disease manifests as a wide range of motor and non-motor symptoms, making individualized treatment essential for improving quality of life.

"Parkinson's isn't just one disease," Malaga says. "It's a collection of symptoms that vary from patient to patient. Our goal is to make DBS as precise and effective as possible, leveraging today's technology to its fullest potential while we continue searching for a cure."

As DBS continues to evolve, studies like Malaga's pave the way for more targeted and effective therapies, offering hope to Parkinson’s patients worldwide. While DBS is not a cure, it represents a vital tool in managing the disease and improving patient outcomes.