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In the new research, during surgery to
implant a permanent DBS device (green with yellow tip) deep in the brains of
Parkinson's disease patients, six recording electrodes (red) were temporarily
placed on the surface of the brain. Credit: C. de Hemptinne
UC San Francisco scientists have discovered a
possible mechanism for how deep-brain stimulation (DBS), a widely used
treatment for movement disorders, exerts its therapeutic effects.
Few medical treatments show results as rapid
and dramatic as those seen with DBS, in which surgically implanted devices
deliver electrical pulses to inner brain structures
involved in movement. In most Parkinson's disease (PD) patients who receive
the treatment, symptoms of slow movement, tremor, and rigidity sharply
diminish soon after the stimulation device is activated, and quickly return
if the device is turned off.
But surprisingly, there has been very little
understanding of precisely why and how DBS works so well—a lack of knowledge
that has held back efforts to further improve the therapy. Despite the great
success of DBS, some significant problems remain. Customizing the stimulation
delivered by DBS devices for each patient to maximally reduce symptoms is
challenging and time-consuming. And a minority of patients never obtains the
full benefit their physicians expect. With a better understanding of how DBS
acts on brain circuits,
researchers hope to address these shortcomings and make DBS an even more
effective treatment.
The new research, published online April 13,
2015 in Nature Neuroscience, reveals that DBS keeps PD symptoms in
check by reducing excessive synchronization of brain activity in the motor cortex, a region
on the outer surface of the brain that governs movements of the body.
"This therapy is becoming widespread for
many brain disorders aside from movement disorders, including psychiatric
conditions such as depression, but no one knows how it works," said
UCSF's Philip Starr, MD, PhD, the Dolores Cakebread Chair in Neurological
Surgery and senior author of the new study. "This is a significant step
in answering this question on the level of brain networks, not just
addressing where you're actually applying the stimulation in the brain."
Previous research led by Coralie de
Hemptinne, PhD, a postdoctoral fellow in Starr's laboratory, laid the
groundwork for the new study. In 2013, de Hemptinne, Starr, and colleagues
reported in the Proceedings of the National Academy of Sciences that a
measure of synchronized rhythmic activity in the brain, which normally varies
with movement or other behaviors, is excessively high in in the cortex in PD.
In that paper, the team hypothesized that
this lockstep synchronization of brain circuits in PD thwarts the flexibility
the brain requires to plan and execute movements, and that DBS might work by
decoupling activity patterns in the motor cortex.
In the new work, "since we had found
this excessive synchrony in PD patients, we decided to see if there's a
relationship between that synchrony and symptoms, and whether synchrony is
lessened when symptoms are improved by DBS," said de Hemptinne, first
author of the Nature Neuroscience paper. "We measured synchrony
in the motor area of the brain before, during, and after DBS, and while the
patient was resting or engaged in a movement task in which they had to reach
and touch a computer screen."
During surgery on 23 patients with Parkinson's
disease in whom permanent DBS electrodes were being surgically implanted, the
UCSF team slid a temporary strip of 6 recording electrodes under the skull
and placed it over the motor cortex. As in the prior research, recordings of
neural activity showed excessive synchronization of activity rhythms in the
patients.
As the name of the therapy implies, the end
of the stimulating lead of DBS devices is placed in a structure deep in the
brain known as the subthalamic nucleus (STN), which is part of a
"loop" of neural circuitry that includes the motor cortex on the
brain's surface. When the DBS device was activated and began stimulating the
STN, the effect of the stimulation reached the motor cortex, where
over-synchronization rapidly diminished. If the device was turned off,
excessive synchrony re-emerged, more gradually in some patients than others.
DBS surgery generally takes about six hours,
and during the middle of the procedure patients are awakened for testing of
the device and to ensure that the stimulating lead is properly placed in the
STN. During this period the researchers asked 12 of the patients to perform a
reaching task in which they had to touch a blue dot appearing on a computer
screen. Importantly, said Starr, recordings revealed that DBS eliminated
excessive synchrony of motor cortex activity and facilitated movement without
altering normal changes in brain activity that accompany movements.
"Our 2013 paper showed how Parkinson's
disease affects the motor cortex, and this paper shows how DBS affects the
motor cortex," said Starr. "With these two pieces of information in
hand, we can begin to think of news ways for stimulators to be automatically
controlled by brain activity, which is the next innovation in the treatment
of movement
disorders."
Because in these experiments the recording
strip had to be removed before the end of surgery, recording data was
collected over a relatively short time. To broaden opportunities for research,
Starr and his team have collaborated with medical device company Medtronic on
a new generation of permanently implantable DBS devices that can record
activity in the motor cortex while delivering stimulation to the STN.
Five UCSF patients have received
with these new devices, and all data they collect can be uploaded for
research during follow-up visits, de Hemptinne said, which will bring an even
deeper understanding of how DBS reshapes brain activity.
"Now we can try to find even better
correlations between DBS and symptoms, and we can even look at the effects of
medications," said de Hemptinne. "This new ability to collect data
over a longer time course will be very powerful in driving new
research."
More information:
Nature Neuroscience, DOI:
10.1038/nn.3997
Journal reference: Nature Neuroscience Proceedings of the National Academy of Sciences
Provided by University of California, San Francisco
http://health.einnews.com/article/259844256/zhlH1IpWvlWEuAAu
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