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Parkinson's, Alzheimer's, Dementia
Engineers Say They Now Know How Brain Pacemakers
Help Parkinson’s Patients
Deep brain stimulation erases diseased messages for
thousands
May 31, 2007 – About 30,000 Americans suffering
from Parkinson’s disease and other movement disorders have “pacemakers”
inserted in their heads. The brain pacemakers are working to ease the
symptoms but even clinical trials leading to their acceptance did not
clearly reveal how they achieved these results. New research has found they
seem to be drowning out the electrical signals of the diseased brains.
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The Food and Drug Administration approved the use
of this deep brain stimulation for Parkinson's disease in 1997. The
electrical implants are also an approved therapy for other movement
disorders and are at various stages of testing for the treatment of
epilepsy, depression, obsessive-compulsive disorder and pain, according
to Warren Grill, the study's lead investigator and an associate
professor of biomedical engineering at Duke University's Pratt School of
Engineering.
But, despite the clinical success of the devices,
the mechanisms by which deep brain stimulation alleviates disease
symptoms aren't well understood.
Biomedical engineers at Duke have found that
stimulation administered by rapid-fire electrical pulses deep in the
brain produces what they call an "informational lesion." By relaying a
repetitious and therefore meaningless message, constant pulses overwhelm
the erratic bursts of brain activity characteristic of disease.
"Periodic bursts in the brains of people with
tremor -- which might follow a pattern such as 'pop-pop-pop, silence,
pop-pop-pop, silence' -- propagate pathological information within brain
circuits," said Grill.
"If you replace that instead with a constant
'pop-pop-pop-pop-pop-pop,' you've erased that pathological information."
Grill said the high-frequency deep brain
stimulation acts like a surgical lesion, another acceptable treatment
for severe tremor disorders and epilepsies. But the electronic device
has the advantage of being adjustable or reversible.
The researchers' report appears in a special June
2007 issue of the journal IEEE Transactions on Neural Systems and
Rehabilitation Engineering, edited in part by Grill. The study was
conducted by a team that included Alexis Kuncel, a doctoral student in
biomedical engineering at Duke, and Scott Cooper, a neurologist at the
Cleveland Clinic, with support from the National Institutes of Health.
The complexity of the brain -- in which nerves
project in all directions and connect with one another to form multiple,
looping networks -- makes studying how deep brain stimulation works a
challenge, Grill said.
Grill's team created a mathematical model of a
normally functioning brain cell. The researchers then gave the model
neuron the pathological pattern of activity seen in people with tremors,
assembled a group of these model cells and watched what would happen
when the cells were electrically stimulated at various rates and
intensities.
In addition to showing how the therapy works, their
model of neurons in action also revealed that stimulation delivered at
too slow a pace fails to keep bad information at bay. Indeed, slower
pulses can actually add to problematic bursts, they showed.
The model's findings closely parallel the clinical
responses of patients, who typically experience the greatest relief from
symptoms when their devices are tuned by physicians to deliver rapid
pulses, Grill said. Patients' symptoms can actually worsen when the
devices are dialed to a slower setting.
The intensity of stimulation also plays an
important role, the study suggests, by determining the number of brain
cells affected by a particular series of pulses.
A better understanding of the processes underlying
deep brain stimulation could enable physicians to better fine-tune
electrical implants, Grill said. That could be particularly useful for
zeroing in on effective settings for implants used to treat diseases,
such as epilepsy, in which seizures occur only sporadically, as well as
conditions, such as depression, in which symptoms can vary widely from
day to day.
"In the case of tremor, physicians can alter the
setting until they see the symptoms stop," Grill said. "You don't have
to know how it's really working.
"In a condition like epilepsy, however, it's
extremely unlikely that a person would have a seizure in the doctor's
office," he said. "Therefore, it might take months of trial and error to
find the optimal setting." Grill's new model promises to streamline the
process.
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