Researchers have developed a method to repurpose existing ultrasound technologies to manipulate neural activity—a process known as neuromodulation—potentially marking a new approach to treating Alzheimer’s disease.
While ultrasound has long been used to monitor fetal development or destroy tumors with high-intensity bursts, using it to directly influence neural activity has only been explored in laboratory settings over the past decade. Some prior studies have identified potential medical applications, such as treating Alzheimer’s and epilepsy; however, this is the first time a device has successfully targeted three to five distinct brain regions simultaneously.
Holographic Ultrasound Neuromodulation
The research team, comprising scientists from ETH Zurich, the University of Zurich, and New York University, has developed a new device that significantly enhances precision when coordinating the stimulation of multiple brain regions simultaneously.
“Given that the brain operates in networks, it’s easier to activate or inhibit a brain network if you stimulate it at multiple points simultaneously,” said co-author Daniel Razansky, a professor at ETH Zurich and the University of Zurich.
In their study, the authors report that “holographic transcranial ultrasound stimulation allows direct control of the stimulated volume and actively modulates local and mid-range network projections,” which they say helps to lower “the activation threshold by an order of magnitude.”
A major advantage of the new device is that it is non-invasive, requiring only placement on top of the subject’s head without any surgical alterations to the skull. While the device has not yet been tested on human volunteers, early neuromodulation tests on mice have shown promising results. In these experiments, the mice’s heads were positioned beneath a hood containing hundreds of miniature ultrasound transducers.
Increasing the Safety of Brain Stimulation
By combining the transducers with precision stimulation electronics, the researchers generated short ultrasound pulses that interfered with one another inside the mice’s brains. Producing many overlapping waves allowed the device to form specific focal points—similar to how a hologram is created by the interaction of light waves. This networked approach, targeting multiple sites simultaneously, increases the device’s overall effect on the brain while operating at a lower intensity than single-focus systems.
“The less intense the ultrasound, the safer this process is for the brain,” Razansky said.
Previous single-focus methods carried significant risks, as researchers often struggled to find the optimal intensity. If the intensity was too low, the ultrasound had no effect; too high, and it risked stimulating the entire brain or even causing tissue damage. High-intensity ultrasound can also overheat brain tissue or harm the vascular system. By contrast, the team’s low-intensity pulses raise temperature only slightly and for extremely short durations, minimizing any thermal effects.
Working Toward Applications
In future research, the team plans to study how ultrasound waves interact with channel proteins—structures on neuron surfaces that regulate the flow of ions in and out of cells. Early evidence suggests ultrasound may influence these proteins, but further study is needed to understand the mechanism in detail. Mastering this relationship could enable more precise activation or inhibition of neurons in various brain therapies.
Another major advantage of the team’s system is that it enables researchers to visualize brain networks in real time as they are being stimulated, offering a powerful new tool for observing the effects of neuromodulation across distributed regions.
Although the new research focuses on demonstrating the device’s neuromodulation capabilities rather than tailoring it for a specific clinical treatment, the team’s findings lay crucial groundwork for future medical applications.
The paper, “Holographic Transcranial Ultrasound Neuromodulation Enhances Stimulation Efficacy by Cooperatively Recruiting Distributed Brain Circuits,” appeared in Nature Biomedical Engineering on July 7, 2025.
Ryan Whalen covers science and technology for The Debrief. He holds an MA in History and a Master of Library and Information Science with a certificate in Data Science. He can be contacted at ryan@thedebrief.org, and follow him on Twitter @mdntwvlf.