Image courtesy of Ken Probst/Starr lab

Deep brain stimulation has been used to treat Parkinson’s
disease symptoms for 25 years, but limitations have led researchers to look for
ways to improve the technique. The first fully implanted DBS system that uses
feedback from the brain itself to fine-tune its signalling is now being tested
by the National Institutes of Health’s Brain Research through Advancing
Innovative Technologies (BRAIN) Initiative and the National Institute of
Neurological Disorders and Stroke (NINDS).

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

Deep brain stimulation is a method of managing Parkinson’s
disease symptoms by surgically implanting an electrode, a thin wire, into the
brain. Traditional deep brain stimulation 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 described in this study 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 deep brain stimulation in human Parkinson’s
disease patients,” said Philip Starr, MD, PhD, 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 deep brain stimulation 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 are 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 recognise a pattern
of brain activity associated with dyskinesia, or uncontrolled movements that
are a side effect of deep brain stimulation 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 minimise deep brain stimulation-related side effects.

Results of initial, short-term studies aimed at demonstrating
feasibility and effectiveness of using adaptive deep brain stimulation to
overcome the impediment to movement of Parkinson’s suggested that this adaptive
approach was equally effective at controlling symptoms as traditional deep
brain stimulation. 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 deep brain
stimulation did not continuously stimulate the brain, the system saved about 40%
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 deep brain stimulation 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 deep brain stimulation 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 Dr
Starr. “Instead, our device receives feedback from the motor cortex, far from
the stimulation source, providing a more reliable signal.”

Many patients with Parkinson’s disease who would benefit
from deep brain stimulation 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 deep brain stimulation, but considerable testing remains
to be done.

“Here we have demonstrated the feasibility of adaptive deep
brain stimulation,” said Dr Starr. “We are now planning larger, longer-term
trials to determine how effective this system is in managing the symptoms of
patients with Parkinson’s disease.”