Ultrasound Could Offer Noninvasive Treatment for Parkinson’s and Depression

The possibility of focusing the beams without ruining tissue could someday diagnose or even restore faulty brain circuits.

A macaque monkey sat in front of a computer. The target –a yellow square – appeared in the periphery on the left side of the screen. After a few moments, another target appeared on the right. The question was: What will the monkey see first?

As far as neuroscience experiments go, the second step was odd. From non-invasively directing bursts of inaudible acoustic energy at a specific visual region of the brain, a group of scientists steered the animal’s responses. If the monkeys focused on the left side of their brain, they would look to the right more frequently and vice versa.

The results of the experiment, that were introduced recently at the yearly Society for Neuroscience meeting, indicated the first time that focused ultrasound was safely and efficiently used at a nonhuman primate to change brain activity rather than destroy tissue. A second study, conducted on sheep, had similar results.

“The finding paves the way to noninvasive stimulation of specific brain areas in humans,” says Jan Kubanek, a neural scientist at Stanford University School of Medicine and lead author of the macaque study.

The technology may ultimately be used to diagnose or cure neurological diseases and ailments like Parkinson’s disease, epilepsy, addiction and depression. Other scientists are also very optimistic.

“The concept that, with a very carefully constructed dose, you may actually deliver [focused ultrasound] and stimulate the brain in the area you want and govern a circuit instead of harm it, is a vital proof of principle,” said Helen Mayberg, MD, of Emory University School of Medicine, who wasn’t involved with the analysis.

Ultrasound has been used for imaging for a very long time now. When sound waves over the level humans can hear (more than 20,000 hertz) are targeted at the entire body, a number of the energy bounces back developing a photo of internal bodily structures.

Focused ultrasound

Focused ultrasound, or FUS, increases the energy level to do different things. Like using a magnifying glass to focus beams of light onto one point and burn off a leaf, FUS concentrates as many as 1,000 solid waves on a specific target with precision.

Initially approved by the Federal Drug Administration in 2004 as a treatment for uterine fibroids, focused ultrasound has gained a huge number of potential uses, creating excitement among doctors. “There are 18 ways, or mechanisms of action, by which this ultrasound affects tissue. That fact creates the chance to take care of a whole variety of health 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 attempts to speed the adoption and development of this technology.

Ten years ago, FUS was researched as a treatment for three diseases/disorders. Now that number stands at over 90. Thus far, however, it’s only been used in people to target and destroy tissue with heat. In addition to uterine fibroids, it’s approved for four other therapeutic applications in the USA. Prostate cancer has been added to the listing in 2015, though some urologists have been uncertain about its use, highlighting in the Journal of the American Medical Association at 2016 that the long-term efficacy is not yet confirmed.

Howard Eisenberg, professor and chief of neurosurgery at the University of Maryland, School of Medicine has found that patients like the technology because it’s less invasive than deep brain stimulation, which requires operation to implant an electrode. “It’s not surgery really,” says Eisenberg.

Comparatively speaking, neuromodulation, that involves altering chemical and electrical signaling in mind circuits, requires lower levels of energy which are delivered as intermittent pulses, and is comparatively far down the list of potential uses for FUS in the mind. “It is a frontier approach,” says Eisenberg, who is more excited about utilizing FUS to open up the blood brain barrier for drug delivery. However if the technique can be perfected as a method of brain stimulation it will open a brand new range of possibilities.

It can be directed more precisely – on the order of millimeters instead of centimeters – compared to transcranial magnetic stimulation (TMS). And it may go deeper in the brain.

“I feel the first opportunity is on the diagnostic side. Disease circuitry might be variable across patients. If we can specifically stimulate areas deep in the brain and measure the reduction of tremor, that will [inform us that region is] involved in that behavior”, said Kubanek. The next step is to apply concentrated ultrasound as a method of brain stimulation for a variety of psychological 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, has shown successful brain stimulation with FUS in the Society for Neuroscience meeting. Yoo and his colleagues showed that FUS could both excite and inhibit brain activity without any evident harm. However, Yoo’s primary aim was to develop a wearable transcranial FUS system. His team created a small device weighing just a quarter of a pound which could be worn by the sheep, whose cranial structure is similar to humans. (In humans, they plan to eliminate the requirement for implantation.) The team also developed a computer algorithm effective at forecasting the intensity and location of the acoustic concentrate, which Yoo likened to an area the size of a large piece of orzo pasta.

“The resources themselves are actually changing the face of what’s possible,” Mayberg says. “It would be great if we can tune [brain circuitry] with ultrasound without having to cut open the brain”, she states. This will prevent surgery and the need for occasionally changing batteries. “We can begin to dream about some inventions that derive from beautiful neuroscience.”


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