Transcranial focused ultrasound: A new way to stimulate the brain

March 25th, 2025

Written by: Joseph Stucynski

You’ve likely heard of ‘getting an ultrasound’ at a hospital to scan an injury or check on the growth of a baby during pregnancy, but have you ever heard of ultrasound being used to stimulate your brain? That’s right! On today’s episode of ‘Wacky Neuroscience Techniques That You Probably Didn’t Know Exist’, we’re here to talk about Focused Ultrasound (FUS) neuromodulation! FUS is a relatively new technique that uses ultrasonic sound waves to temporarily turn on or off specific brain regions. Before you ask, you can go ahead and put away your tinfoil hats – nobody is coming to microwave your brain.  Rather, by using many low intensity sound waves that only overlap at one point in the brain to produce effects, FUS can safely modulate brain regions as small as 1 cubic millimeter deep in the brain.¹ FUS shows great promise as a tool for asking how neurons communicate together to produce various behaviors in animals as well as humans non-invasively, meaning without having to implant devices into the brain. Moreover FUS, researchers might be able to help patients with treatment resistant psychiatric disorders that require more specific therapeutic approaches.

What is FUS and how does it work?

As early as 1929, ultrasonic sound waves, which are above the 20,000 hertz hearing range of humans, were known to produce effects in biological tissues. For instance, high intensity sound waves (unlike those used in ultrasound scans today) could effectively stimulate heart muscles and nerves in frogs.² While several experiments in the following decades even showed that ultrasonic waves could impact brain tissue, it wasn’t until 2010 that neuroscientists demonstrated that aiming these waves at the brain’s motor cortex could produce muscle twitches in mice.³

While the physics of ultrasonic stimulation of brain tissue is very complicated, you can start by imagining multiple sound beams aimed at a particular point in the brain. When the sound beams intersect in the brain, they cause the neurons at that point of overlap, called the focal point, to become active.¹

At this point you might be asking, ‘how does a sound wave even activate neurons?’ While the exact mechanisms are still under investigation, it comes down to physical changes like mechanical vibrations and changes in temperature. Neurons become active when enough electrical signals pass through their membranes. This electricity is controlled by the flow of ions like sodium, potassium, chloride, and calcium across openings in the membranes called ion channels. As it turns out, lots of these ion channels can open and close in response to mechanical vibrations and temperature changes, just like those produced by FUS. This means that FUS can produce brain activity wherever neuroscientists aim the overlapping sound beams. And what’s new and great about FUS is that this ultrasonic focal point can be deep in the brain where other stimulation techniques would not be able to target.

Initially there were concerns that beaming high-intensity ultrasonic sound waves into the brain could be unsafe. Scientists worried about things like overheating brain tissue or causing physical damage. However, studies in animals have showed that at low intensity, FUS waves can not only effectively modulate brain activity, but in some cases can even cool tissue temperature down by modifying blood flow in the brain.⁴ Thus far, low intensity FUS has been deemed safe and has had no harmful effects in human subjects.¹

FUS was also recently employed in mice to better understand which ultrasonic stimulation parameters or settings can be used to activate specific types of neurons, and turn on some while turning off others.⁴ Such stimulation parameters of FUS include the frequency of sound pulses, as well as their intensity. Since different neurons throughout the brain have different ion channels, the researchers find that varying how the sound is delivered has a big effect on whether it turns them on or off. And in fact, they find that some brain regions don’t respond to the stimulation at all. Additionally, their study is one of, if not the first, to show that FUS can produce complex behavioral responses in mice – a fact which might eventually lead to more precise stimulation treatments in humans.

How is FUS being used?

Since FUS is non-invasive, and can target very small regions that are deep in the brain, it provides an alternative to surgically implanting devices for brain stimulation in both monkeys and humans, which is risky and can lead to unwanted side effects. In humans, FUS is being tested in numerous clinical trials at the moment to see whether it can help treat disorders of consciousness like coma after brain injury, muscle tremors like in Parkinson’s disease,⁵ depression,⁸ and treatment resistant epilepsy.¹

The first example of FUS being clinically tested in humans occurred in 2016 on a patient who went into a coma after a serious brain injury. The researchers stimulated portions of the thalamus, which is thought to act as a gate of consciousness in the brain. They reported that 3 days after stimulation, the patient’s level of coma improved.^1,6

Another application of FUS saw researchers precisely targeting a region of the thalamus while administering a hot, painful stimulus.⁷ This stimulation of the thalamus was able to increase the participants’ pain threshold, meaning they could tolerate more pain. This may lead to future studies of FUS being used for pain reduction in a variety of contexts.

Ultrasonic stimulation of the right fronto-temporal cortex, an area of the brain associated with mood, in college students with mild-to-moderate depression was also able to improve their mood slightly and reduce the amount that they worried.⁸ While it did not decrease their overall depression symptoms in this case, a similar study found that using FUS to stimulate brain areas associated with depression could alter the global activity in brain networks back to a more normal state not associated with depression.⁹

Since ultrasonic stimulation has only taken off in the last 5 years or so,^1,4 many new applications are still being tested. While there’s lots to investigate, study, and develop, ultrasonic stimulation will most assuredly become another important tool in the neuroscientist’s toolkit, and hopefully lead to many new disease treatments in the future.

References

1. Darmani G., Bergmann T., Butts Pauly K., Caskey C., de Lecea L., Fomenko A., Fouragnan E., Legon W., Murphy K., Nandi T., Phipps M., Pinton G., Ramezanpour H., Sallet J., Yaakub S., Yoo S., Chen R. Non-invasive transcranial ultrasound stimulation for neuromodulation. Clinical Neurophysiology, 2021.
2. Harvey, E. The effect of high frequency sound waves on heart muscle and other irritable tissues. American Journal of Neurophysiology, 1929.
3. Tufail Y., Matyushov A., Baldwin N., Tauchmann M., Georges J., Yoshihiro A., Tillery S., Tyler W. Transcranial pulsed ultrasound stimulates intact brain circuits. Neuron, 2010.
4. Murphy K., Farrell J., Bendig J., Mitra A., Luff C., Steltzer I., Yamaguchi H., Angelakos C., Choi M., Bian W., Dilanni T., Pujol E., Matosevich N., Airan R., Gaudilliere B., Konofagou E., Butts Pauly K., Soltesz I., de Lecea L. Optimized ultrasound neuromodulation for non-invasive control of behavior and physiology. Neuron, 2024.
5. Kubanek J. Neuromodulation with transcranial focused ultrasound. Neurosurgical Focus, 2018.
6. Monti M., Schnakers C., Korb A., Bystritsky A., Vespa P. Non-invasive ultrasonic thalamic stimulation in disorders of consciousness after severe brain injury: A first-in-man report. Brain Stimulation, 2016.
7. Badran B., Caulfield K., Stomberg-Firestein S., Summers P., Dowdle L., Savoca M., Li X., Austelle C., Short B., Borckardt J., Spivak N., Bystritsky A., George M. Sonication of the anterior thalamus with MRI-guided transcranial focused ultrasound (tFUS) alters pain thresholds in healthy adults: A double-blind, sham-controlled study. Brain Stimulation, 2020.
8. Reznik S., Sanguinetti J., Tyler W., Daft C., Allen J. A double-blind pilot study of transcranial ultrasound (TUS) as a five-day intervention: TUS mitigates worry among depressed participants. Neurology, Psychiatry, and Brain Research, 2020.
9. Sanguinetti J., Hameroff S., Smith E., Sato T., Daft C., Tyler J., Allen J. Transcranial focused ultrasound to the right prefrontal cortex improves mood and alters functional connectivity in humans. Frontiers in Human Neuroscience, 2020.

Cover image by Pawel Czerwinski via Unsplash.com