Journal Club

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Journal Club: Low-intensity focused ultrasound shows promise as tool to probe deep brain function

The deep brain is hard to reach without invasive surgery. Recent work suggests low intensity focused ultrasound could serve as a promising, minimally invasive tool to stimulate deep brain regions and change their activity for long periods.                                Image credit: Deaff/ Shutterstock.

The deep brain is hard to reach without invasive surgery. Recent work suggests low-intensity focused ultrasound could serve as a promising, minimally invasive tool to stimulate deep brain regions and change their activity for long periods.
Image credit: Deaff/ Shutterstock.

To study the brain’s networks of neurons, neuroscientists typically alter the activity in one area, and observe the cascade of effects on others—something like unscrewing one bulb in a string of Christmas lights and observing as others go dim.

But changing deep brain activity, which often entails surgery and implanting electrodes, can be invasive. A study, recently published in Neuron, found that ultrasound may be a good, minimally invasive candidate to reversibly change activity for long periods, deep in the primate brain.

Using low-intensity focused ultrasound, neuroscientist Davide Folloni, of the University of Oxford, stimulated the amygdala and anterior cingulate cortex in the macaque brain. The stimulation changed each region’s activity for up to two hours, impairing its ability to communicate with other brain areas to which it’s tightly coupled. The research group concurrently published a second paper in eLife, using the same methodology to modulate regions of the frontal cortex, near the brain’s surface, which also showed prolonged effects of ultrasound stimulation.

“Focused ultrasound has been used to modulate brain activity for a while,” says neuroscientist Jamie Tyler at Arizona State University. But the new research “showed long-lasting changes in network activity,” he notes. “That’s unique.”

For the Neuron study, Folloni applied low-intensity focused ultrasound stimulation to the shaved heads of anesthetized macaque monkeys. A beam of sound waves moved from the ultrasound machine deep into their brains, to the amygdala or anterior cingulate cortex. After sonicating for 40 seconds, the researchers moved each monkey into an fMRI scanner to record the brain’s activity at rest.

Every brain region has a characteristic activity pattern, Folloni explains, and functionally connected regions engage in activity at the same time, which the fMRI detects. After stimulating an area with ultrasound, the amygdala for example, the fMRI scans showed that the area had less capacity to communicate with functionally-related brain areas. In other words, these areas didn’t light up with activity at the same time. Researchers should be able to figure out the role of a stimulated region by observing what changes, says behavioral neuroscientist and study coauthor Jerome Sallet, also of Oxford.

The study is among the first to reach new depths of the brain with a noninvasive, spatially-specific tool. Similar previous ultrasound work has probed deep areas, such as the thalamus, Tyler points out, but never with such a sensitive fMRI analysis that detected altered brain activity for so long. A prolonged response makes focused ultrasound a much more promising tool to study the brain, and, potentially, to treat it.

Mental health conditions such as anxiety and depression are linked to deep brain regions. Now that low-intensity focused ultrasound has demonstrated lasting effects, the researchers foresee clinical applications in humans. Folloni suggests, for example, that the technique could eventually be used to transiently target either deep and subcortical brain areas, or more superficial regions in a more focused fashion.

Tyler envisions perhaps using this ultrasound approach as a precursor to deep brain stimulation (DBS), in which electrodes are implanted to treat disease. Doctors might stimulate candidate areas of the brain with ultrasound, he says, to assess if patients will respond well to DBS treatment, and to find the best placement for electrodes before surgery.

The authors urge caution, however, because soundwaves also apply pressure to brain tissue. In the eLife paper, the group did conduct histological analyses after sonication of macaque brain, and found no signs of lesions or edema.

The work also contributes to fundamental neuroscience, Folloni says, because changing the activity of deep regions can help “establish the functional role of these regions,” to better understand the entire brain.

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