New Parkinson’s Findings May Impact DBS Therapies

by James Cavuoto, editor

June 2021 issue

Neurologists and neurosurgeons treating individuals with Parkinson’s disease have used deep brain stimulation to help hundreds of thousands of patients who do not respond to pharmaceutical interventions, such as L-dopa. But neuromodulation therapy has also helped shed light on the underlying cause of the disease, which in turn informs new therapeutic approaches.

In 2018, Philip Starr, at UCSF developed an adaptive version of DBS that adapts its stimulation only when needed based on recorded brain activity. More recently, Starr and his colleagues described in Nature Biotechnology several additional improvements to the implanted technology. “This is the first device that allows for continuous and direct wireless recording of the entire brain signal over many hours,” said Starr. “That means we are able to perform whole brain recording over a long period of time while people are going about their daily lives.”

The implications of this type of recording are significant. The brain activity patterns normally used to identify problems such as Parkinson’s disease symptoms have traditionally been recorded in clinical settings over short periods of time. This new technology makes it possible to validate those signatures during ordinary daily activities. “If you ever hope to use in-hospital recordings to modify a disease state through adaptive stimulation, you must show that they are also valid in the real world,” said Starr.

Another advantage to recording over long periods of time is that biomarkers that could predict movement disorders can now be identified for individual patients. Ro’ee Gilron, a postdoctoral scholar in Starr’s lab and first author of the study, explained that this allows for a level of customized DBS treatment that was impossible to achieve previously.

“Because we are able to build a biomarker library for each patient, we can now program each DBS unit according to a patient’s individual needs,” said Gilron. “This includes personalized stimulation programs that adapt as the patient’s needs change throughout the day.”

A team led by Andres Lozano and colleagues at the University of Toronto and GE Global Research recently published an article in Nature Communications proposing that fMRI responses to DBS stimulation in PD patients could represent an objective biomarker of clinical response.

The team analyzed fMRI data prospectively acquired as part of an observational trial in 67 PD patients using optimal and nonoptimal stimulation settings. They found that clinically optimal stimulation produced a characteristic fMRI brain response pattern marked by preferential engagement of the motor circuit.

At the recent NIC conference, Parag Patil from the University of Michigan argued for moving away from brain-atlas based targeting in STN DBS for PD. Instead, he used high-resolution MRI imaging combined with electrophysiological recordings to personalize the optimal location. The techniques helped his team identify regions of peak beta oscillations.

Perhaps a more profound change in thinking about PD has been put forward by Jonathan Sackner-Bernstein, a former FDA official. Publishing in Journal of Parkinson’s Disease, he posited that the standard way to treat Parkinson’s might be the opposite of what would be the most effective. His study showed that instead of focusing on increasing brain dopamine in Parkinson’s patients, a more scientifically rational approach would be to reduce the amount of dopamine within the cells in the brain that control movement.


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