A recent study led by researchers at NYU Langone Health, the University of Zurich, and ETH Zurich has demonstrated that brain circuits in living animals can be activated using ultrasound waves shaped into specific patterns known as holograms. The findings were published online in Nature Biomedical Engineering on July 7.
The research team developed a system that uses multiple sources of ultrasound waves along with a fiberscope and camera to visualize which areas of the mouse brain are activated by these sound waves. This method allows for targeted stimulation of neurons without the need for invasive procedures. Unlike current FDA-approved treatments for Parkinson’s disease tremors—which use high-intensity ultrasound to destroy neurons—this new approach employs lower-intensity ultrasound to temporarily activate neurons. The technique could lead to new ways of treating neurological and mental health disorders externally.
The study highlights the challenge of observing transcranial ultrasound stimulation (TUS) effects in a living brain, as opposed to studying isolated neurons in laboratory dishes. For TUS therapy to be both safe and effective, it is necessary to direct the ultrasound precisely at intended brain regions while ensuring the intensity is sufficient to penetrate the skull but not so strong as to harm brain tissue.
In their experiments, researchers used a helmet-shaped array containing 512 ultrasound emitters placed above the mouse’s head. By coordinating these emitters, they created holograms—three-dimensional patterns made from sound waves—that could focus on specific regions of the brain. As targeted neurons became active, they emitted fluorescence signals that were captured by a camera, allowing measurement of how different regions responded.
“Our work shows that activating entire sets of neural networks with transcranial ultrasound stimulation in a living mouse brain is possible,” said Shy Shoham, PhD, co-senior author and codirector of the Tech4Health Institute at NYU Langone Health. Daniel Razansky, PhD, at the University of Zurich and ETH Zurich served as co-senior author.
“We also found that, by focusing on circuits of neurons that are distributed across brain regions rather than in any individual region, TUS leverages inter-connections within the circuits to make targeted neurons 10 times more sensitive to ultrasound,” Dr. Shoham said. “This discovery potentially makes the technique more efficient, lowers the ultrasound power required, and could pave the way to safer transcranial ultrasound stimulation treatments in the future.”
According to Dr. Shoham: “Our findings provide new insights into how transcranial ultrasound stimulation activates circuits within a living organism. We hope the techniques and computational models we’ve developed will help other basic researchers probe the mechanisms of different brain circuits. Ultimately, our goal is to translate this work into transcranial ultrasound stimulation protocols to treat different human conditions, such as mental health disorders.”
The team plans further studies aimed at activating more complex neural circuits and testing whether deeper brain regions can be stimulated using this method.
Funding for this research was provided by grants from the National Institutes of Health (RF1NS126102 and R01NS109885) and additional support from the Swiss National Science Foundation.
Postdoctoral fellow Théo Lemaire was an NYU Langone co-investigator on this project. Other contributors included Hector Estrada (first author), Yiming Chen, Neda Davoudi, Ali Özbek, and Qendresa Parduzi from University of Zurich and ETH Zurich.
