Summary: Researchers have created a novel ultrasound device that can non-invasively stimulate several precisely defined points in the brain at the same time. This represents a major advance in transcranial neuromodulation: by using hologram-like wave interference and lower-intensity pulses, the method reduces risks such as overheating and uncontrolled excitation while improving control over which brain networks are targeted.
The technique also enables simultaneous visualization of the induced neural activity, allowing researchers to see in real time which circuits are being engaged. Although the current results come from early animal experiments, the approach could pave the way for new therapies for neurological and psychiatric disorders.
Key Facts
- Multi-point precision: Stimulates three to five targeted brain regions simultaneously using holographic interference of ultrasound waves.
- Lower intensity, greater safety: Cooperative multi-site stimulation reduces required acoustic power, lowering the risk of thermal or vascular damage.
- Potential applications: The technology could eventually support treatments and research into Alzheimer’s disease, epilepsy, tremor, Parkinson’s disease, depression, and stroke recovery.
Source: ETH
From simple prenatal scans to precise brain modulation
Ultrasound is a familiar tool in medicine: obstetric imaging is perhaps the most common example, while physiotherapists use ultrasound for tissue heating and surgeons employ high-intensity focused ultrasound to ablate tumours. In recent years, researchers have also explored how low-intensity ultrasound can influence neuronal activity in a targeted, non-invasive way — a field known as ultrasonic neuromodulation.
A team from ETH Zurich, the University of Zurich and New York University has developed an improved approach to ultrasonic brain stimulation. Their device uses several hundred individually controlled ultrasound transducers arranged in a hood placed on the head. By precisely timing and shaping brief ultrasound pulses, the transducers produce interfering waves that converge into multiple focal points within the brain — similar in principle to how holograms form three-dimensional images through light-wave interference.
Through the skull
Because the device operates transcranially, it does not require any surgical opening of the skull or implanted hardware. The researchers demonstrated the method in mice by positioning the animal’s head inside the transducer array and directing short, carefully calibrated pulses through the skull. The interference pattern creates multiple, spatially distinct foci that can be steered dynamically.
Delivering stimulation across several locations at once allows effective modulation of distributed brain networks while lowering the intensity delivered to any single point. Lower acoustic intensity reduces the chance of overheating or causing vascular and tissue damage — a key safety advantage compared with some earlier single-spot approaches, which could produce either no effect at low power or risky widespread excitation at high power.
Mechanical influence on proteins
Low-intensity focused ultrasound pulses produce short-lived effects that can include small, localized temperature changes. In addition, the mechanical waves are thought to act on ion channel proteins and other mechanosensitive elements in the neuronal membrane, altering ion flow and excitability. The exact balance of thermal, mechanical and molecular mechanisms that drive activation or inhibition of neurons remains a subject for further study.
A crucial feature of the new setup is the ability to visualize neural responses while stimulating. By combining stimulation with imaging, researchers can monitor which networks are recruited and refine stimulation parameters in real time, improving precision and interpretability of neuromodulation experiments.
The study, published in Nature Biomedical Engineering, focused on developing and validating the technology rather than providing clinical evidence. The results demonstrate improved steering, focality and efficacy of transcranial ultrasound stimulation in animal models, and they lay groundwork for future translational research.
Animal experiments are essential to this research
The project and the collaboration with New York University received primary funding from the United States National Institutes of Health. However, political changes affecting international funding relationships mean the original funding pathway is no longer available; the researchers plan to continue work with alternative support. Their next steps include testing the technology in a range of animal models of brain disease to evaluate safety, control and therapeutic potential.
“Animal studies are indispensable at this stage,” says Daniel Razansky of ETH Zurich and the University of Zurich, who led the work together with colleagues at New York University. “We cannot responsibly move to human trials until we fully understand how to control the intervention and ensure its safety and effectiveness.”
Razansky’s group specialises in ultrasound and optical imaging system engineering, experimental methods and data analysis; collaborating neuroscientists contributed expertise in brain function and circuit-level interpretation. Device development and experiments were carried out in Zurich.
Key Questions Answered
A: For the first time, researchers can non-invasively and precisely stimulate three to five separate brain regions at the same time using holographic ultrasound interference.
A: Because the brain operates as interconnected networks, stimulating multiple nodes simultaneously makes it easier to modulate circuit-level activity safely and effectively.
A: Potential applications include research and treatment for Alzheimer’s disease, epilepsy, tremor, Parkinson’s disease, depression and stroke rehabilitation.
About this ultrasound and neurotech research news
Author: Marianne Lucien
Source: ETH
Contact: Marianne Lucien – ETH
Image: The image is credited to Neuroscience News
Original Research: Open access. “Holographic transcranial ultrasound neuromodulation enhances stimulation efficacy by cooperatively recruiting distributed brain circuits” by Daniel Razansky et al., Nature Biomedical Engineering. DOI: 10.1038/s41551-025-01449-x
Abstract
Holographic transcranial ultrasound neuromodulation enhances stimulation efficacy by cooperatively recruiting distributed brain circuits
Precision-targeted ultrasonic neuromodulation holds significant promise for studying brain function and for treating neurological disorders. However, its utility has been limited by challenges in achieving precise spatio-temporal control and in directly monitoring the effects of ultrasound on distributed brain circuits.
We demonstrate that transcranial ultrasound can produce direct, highly focal responses that are dynamically steerable at spatio-temporal scales relevant to neural processing. Using holographic stimulation, the stimulated volume can be shaped and multiple local and mid-range network projections can be modulated cooperatively, lowering the activation threshold by roughly an order of magnitude compared with single-focus stimulation.
To explain this novel excitability regime, we developed a dual modelling framework combining empirical and mechanistic models that capture key aspects of holographic transcranial ultrasound stimulation. The models align qualitatively with experimental observations and indicate that cooperative network interactions play a major role in the enhanced efficacy.
These findings clarify complex mechanisms by which ultrasound interacts with neural tissue and underscore the potential of holographic transcranial ultrasound for noninvasively interfacing distributed brain networks.