A macaque monkey sat in front of a computer.
A yellow square—the target—appeared in the periphery on the left side of the
screen. After a few seconds delay, a second target appeared on the right. The
question was: Which target would the monkey look at first? So far so routine as
neuroscience experiments go, but the next step was unusual. By non-invasively
directing bursts of inaudible acoustic energy at a specific visual area of the
brain, a team of scientists steered the animal’s responses. If they focused on
the left side of the brain, the monkey looked to the right more often. If they
focused on the right side, the monkey looked to the left more often.
The results of the experiment, which were presented last week at
the annual Society for Neuroscience meeting, marked the first time that focused
ultrasound was safely and effectively used in a nonhuman primate to alter brain
activity rather than destroy tissue. A second study, in sheep, had similar
results. “The finding paves the way to noninvasive stimulation of specific
brain regions in humans,” says Jan Kubanek, a neural engineer at Stanford
University School of Medicine and lead author of the macaque study. The
technology might ultimately be used to diagnose or treat neurological diseases
and disorders like Parkinson’s disease, epilepsy, addiction and depression.
Other scientists are optimistic.
“The idea that, with a very carefully designed
dose, you could actually deliver [focused ultrasound] and stimulate the brain
in the place you want and modulate a circuit rather than damage it, is a really
important proof of principle,” said Helen Mayberg, MD, of Emory University
School of Medicine, who was not involved with the study.
Ultrasound has long been used for imaging. When sound
waves above the level that humans can hear (more than 20,000 hertz) are aimed
at the body, some of the energy bounces back creating a picture of internal
bodily structures. Focused ultrasound, or FUS, raises the energy level to
accomplish other ends. Like using a magnifying glass to focus beams of light on
a single point and burn a leaf, FUS concentrates as many as 1,000 sound waves
on a specific target with precision and accuracy.
First approved by the Federal Drug
Administration in 2004 as a treatment for uterine fibroids, focused ultrasound
has gained an increasing variety of potential uses, generating excitement among
many doctors. “There are 18 ways, or mechanisms of action, by which focused
ultrasound affects tissue. That fact creates the opportunity to treat a whole
variety of medical disorders,” says Neal Kassell, MD, former co-chair of
neurosurgery at the University of Virginia and founder and chairman of the
Focused Ultrasound Foundation, which seeks to speed the development and
adoption of the technology.
A decade ago, FUS was being investigated as
a treatment for three diseases or disorders. Today that number stands at more
than 90. Thus far, however, it has only been used in humans to target and
destroy tissue with heat. In addition to uterine fibroids, it is approved for four
other therapeutic uses in the United States. Prostate cancer was added to the
list in 2015, although some urologists have been lukewarm about its use,
emphasizing in the Journal
of the American Medical Association in 2016
that the long-term efficacy is not yet proven. In the brain, the FDA approved
its use as an ablation treatment (removing tissue) for essential tremor in
2016. (In Europe, it’s more widely used.)
Howard Eisenberg, professor and chief of neurosurgery at
the University of Maryland School of Medicine, participated in the clinical
studies of FUS as an ablative treatment for essential tremor and Parkinson’s
disease, targeting different brain areas for each disorder. He has found that
patients like the technology because it’s less invasive than deep brain
stimulation, which requires surgery to implant an electrode. “It’s not surgery
really,” says Eisenberg. In addition, because FUS is so precise, says
Eisenberg, “you can sculpt the lesion, you might make three ablations all close
to each other.”
Comparatively speaking, neuromodulation, which entails
altering electrical and chemical signaling in brain circuits, requires lower
doses of energy that are delivered as intermittent pulses, and is relatively
far down the list of possible uses for FUS in the brain. “It’s a frontier
approach,” says Eisenberg, who is more excited about using FUS to open the
blood brain barrier for drug delivery But if the technique can be perfected as
a method of brain stimulation it will open a new range of possibilities. It can
be aimed more precisely—on the order of millimeters rather than
centimeters—than transcranial magnetic stimulation (TMS). And it can go deeper
into the brain.
“I think the first opportunity is on the diagnostic side,” said
Kubanek. “Disease circuitry might be variable across patients. If we can
specifically stimulate regions deep in the brain and measure the reduction of
tremor, that would [tell us that region is] involved in that behavior.” The
next step would be to apply focused ultrasound as a method of brain stimulation
for a variety of mental health and neurodegenerative disorders like
Alzheimer’s.
Like Kubanek, Seung-Schik Yoo, professor of radiology at
Harvard Medical School and director of the neuromodulation lab at Brigham and
Women’s Hospital, demonstrated successful brain stimulation using FUS at the
Society for Neuroscience meeting. In sheep, Yoo and his colleagues showed that
FUS could both excite and inhibit brain activity without apparent harm. But
Yoo’s primary aim was to develop a wearable transcranial FUS system. His team
created a small apparatus weighing only a quarter of a pound that could be worn
by the sheep, whose cranial structure is similar to humans.
The system
consisted of a focused ultrasound transducer to generate the signal, an optical
tracker and an applicator to hold the transducer over the head via an implanted
pedestal. (In humans, they plan to do away with the need for implantation.) The
group also developed a computer algorithm capable of predicting the intensity and
location of the acoustic focus, which Yoo likened to an area the size of a
large piece of orzo pasta.
“The tools
themselves are really changing the face of what’s possible,” Mayberg says.
“Wouldn’t it be great if we could tune [brain circuitry] with ultrasound and
don’t have to open the brain?” she says. That would avoid surgery and the need
for periodically changing batteries. “You could wear a device like the sheep,”
she adds. “We can start to dream about some innovations that are based on
exquisite neuroscience.”
https://www.scientificamerican.com/article/ultrasound-could-offer-noninvasive-treatment-for-parkinson-rsquo-s-and-depression/
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