UCSF Team Demonstrates Adaptive DBS for Parkinson’s

by James Cavuoto, editor

May 2018 issue

In recent years, neural engineers and clinicians have begun to investigate closed-loop neuromodulation systems that modify stimulation parameters based upon feedback from neurological signals or neuromuscular response. Saluda Medical has made progress with its closed-loop spinal cord stimulation system for chronic pain. In 2005, a Canadian firm called Medtrode sought to develop a closed-loop DBS platform [NBR Jul06 p6] but commercial progress stalled in subsequent years.

Earlier this month, a team of researchers at UC San Francisco published a study that describes a fully implanted DBS system that uses feedback from the brain itself to fine-tune its signaling. The study was supported by the NIH’s BRAIN Initiative and the National Institute of Neurological Disorders and Stroke.

“The novel approach taken in this small-scale feasibility study may be an important first step in developing a more refined or personalized way for doctors to reduce the problems patients with PD face every day,” said Nick Langhals, program director at NINDS and team lead for the BRAIN Initiative.

Traditional DBS delivers constant stimulation to the basal ganglia to help treat the symptoms of Parkinson’s. However, this approach can lead to unwanted side effects, requiring reprogramming by a trained clinician. The new method is adaptive, so that the stimulation delivered is responsive in real time to signals received from the patient’s brain.

“This is the first time a fully implanted device has been used for closed-loop, adaptive DBS in human PD patients,” said Philip Starr, professor of neurological surgery, University of California, San Francisco, and senior author of the study, which was published in the Journal of Neural Engineering.

In a short-term feasibility trial, two patients with Parkinson’s received a fully implanted, adaptive DBS device. The device differs from traditional ones in that it can both monitor and modulate brain activity. In this work, sensing was done from an electrode implanted over the primary motor cortex, a part of the brain critical for normal movement. Signals from this electrode were then fed into a computer program embedded in the device, which determines whether to stimulate the brain. For this study the researchers taught the program to recognize a pattern of brain activity associated with dyskinesia that are a side effect of DBS in Parkinson’s disease, as a guide to tailor stimulation. Stimulation was reduced when it identified dyskinesia-related brain activity and increased when brain sensing indicated no dyskinesia to minimize deep brain stimulation-related side effects.

Results of initial, short-term studies aimed at demonstrating feasibility and effectiveness of using adaptive DBS to overcome the impediment to movement of PD suggested that this adaptive approach was equally effective at controlling symptoms as traditional DBS. Doctors saw and patients noticed no differences in the improvement in movement under adaptive stimulation versus constant, open loop stimulation set manually by the researchers. Because adaptive DBS did not continuously stimulate the brain, the system saved about 40 percent of the device’s battery energy used during traditional stimulation. The short time periods over which movement was assessed did not permit comparison of the two DBS paradigms relative to incidence of dyskinesia, but it is hoped that the variable stimulation will also translate into a reduction in adverse effects when tested over longer time periods.

“Other adaptive DBS designs record brain activity from an area adjacent to where the stimulation occurs, in the basal ganglia, which is susceptible to interference from stimulation current” said Starr. “Instead, our device receives feedback from the motor cortex, far from the stimulation source, providing a more reliable signal.”

Many patients with PD who would benefit from DBS are difficult to treat because too much stimulation can cause dyskinesia. Thus, finding the correct level of stimulation is like trying to hit a constantly moving target. An adaptive system like the one being tested here could offer an effective alternative and may also limit adverse effects of traditional DBS, but considerable testing remains to be done.

“Here we have demonstrated the feasibility of adaptive DBS,” said Starr. “We are now planning larger, longer-term trials to determine how effective this system is in managing the symptoms of patients with PD.”


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