Transcranial Focused Ultrasound Stimulation (tFUS)?

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Targeted neuromodulation with sound waves: a new development in neuroscience

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The brain consists of various networks that are constantly exchanging information. These networks play an important role in processes such as pain processing, emotions, attention, and behavior.

In certain neurological and psychiatric conditions, changes can occur in the activity and mutual interaction of these brain networks.

Neuromodulation attempts to influence this activity in a targeted manner. In addition to existing techniques such as transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (tES), a new technology is currently being investigated: transcranial focused ultrasound stimulation (tFUS).

This technique offers the ability to reach specific brain regions with high spatial precision, including structures located deeper in the brain.

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What is tFUS?

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Transcranial Focused Ultrasound, abbreviated as tFUS, is a technique in which ultrasonic sound waves are directed through the skull to a predetermined brain region.

Ultrasound consists of sound waves with a frequency that lies outside the normal human hearing range.

During stimulation, a transducer—a device that produces ultrasonic waves—is placed against the head. The sound waves are focused on a specific location in the brain.

In this way, acoustic energy can be transferred to a targeted brain region without the need for a surgical procedure.

The goal of tFUS neuromodulation is to temporarily influence the activity of nerve cells and communication within brain networks.

A major advantage of this technology is that both superficial and deeper brain structures can be reached.

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How does tFUS work in the brain?

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Nerve cells communicate via electrical and chemical signals. Their activity is determined by factors including the properties of the cell membrane, ion channels, and connections with other nerve cells.

With tFUS, focused ultrasonic pressure waves transmit mechanical forces to brain tissue.

Scientists are investigating how these forces influence the functioning of nerve cells. A key hypothesis is that ultrasonic stimulation can affect mechanically sensitive ion channels, which may alter the excitability of nerve cells.

Depending on the chosen stimulation parameters and the brain region involved, various effects can occur.

Research indicates that under certain conditions, tFUS can cause changes in:

• nerve cell excitability;
• communication between brain regions;
• the activity of functional brain networks;
• brain rhythms and electrical oscillations;
• processes involved in neuroplasticity.

Neuroplasticity is the brain's ability to adapt its functioning and internal connections.

The precise mechanism of action for tFUS has not yet been fully elucidated. Furthermore, it has not been established that a specific stimulation protocol produces the same effect in every individual.

A 2026 study, published in Nature Communications, for example, showed that tFUS in combination with electrical stimulation could produce a locally measurable effect on brain activity. However, the researchers did not find a comparable, site-specific response in their EEG measurements when using tFUS alone.

This underscores that the effect of tFUS can depend on the parameters used and the conditions under which the stimulation is applied.

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What is the difference between tFUS and TMS or tDCS?

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TMS, tDCS, and tFUS are all non-invasive neuromodulation techniques, but they operate on different principles.

WithTMS uses a magnetic field to induce electrical currents in brain tissue.

WithtDCS uses a weak electrical current delivered via electrodes on the scalp to influence the excitability of nerve cells.

WithtFUS uses focused ultrasonic pressure waves.

A key difference is the combination of reach and spatial precision.

TMS and tDCS can influence the activity of brain networks, but their direct stimulation is primarily focused on relatively superficial brain regions.

In contrast, tFUS can also directly reach deeper brain structures with a relatively small focal area.

This makes tFUS interesting for research into brain regions involved in complex neurological and psychiatric conditions.

This does not automatically mean that tFUS is more effective than existing techniques. Direct comparative clinical studies are necessary for that.

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What is the difference between low-intensity and high-intensity focused ultrasound?

Not all applications of focused ultrasound stimulation are the same.

There is a fundamental distinction between techniques that attempt to influence brain activity and techniques that deliberately disable brain tissue.

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Low-Intensity Focused Ultrasound (LIFU)

LIFU uses ultrasonic waves with a relatively low intensity.

The goal is to influence the activity of nerve cells without intentionally damaging the brain tissue.

This form of neuromodulation is being investigated for various neurological and psychiatric applications.

The effects are, in principle, non-ablative: no permanent injury is intended. However, this does not mean that all effects necessarily disappear immediately or that the safety of every protocol is already fully understood.

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High-Intensity Focused Ultrasound (HIFU)

HIFU uses a much higher energy concentration.

In certain neurosurgical applications, this energy is used to heat a very specific part of the brain tissue in a controlled manner and permanently disable it.

This technique is used for, among other things, selected movement disorders.

Non-ablative neuromodulation with LIFU should therefore not be confused with the tissue-destroying applications of HIFU.

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What potential applications are being investigated?

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Scientific interest in tFUS is growing, primarily because the technique provides access to brain structures that are difficult to reach directly with other non-invasive stimulation techniques.

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Chronic pain

Pain is not processed in just one area of the brain. Various brain networks contribute to the physical perception of pain, its emotional significance, and the attention given to it.

Researchers are studying whether tFUS can target these networks.

A 2026 study in the journal Research investigated the medial prefrontal cortex in mice with long-term postoperative pain following sleep deprivation during adolescence.

The researchers found that targeted ultrasound stimulation reduced pain sensitivity and caused changes in nerve cell activity, synaptic processes, and brain rhythms.

This research offers new insights into potential mechanisms of action, but it is an animal study. The results cannot be directly translated into a proven treatment for humans with chronic pain.

Initial studies on the stimulation of pain-processing brain structures, including the thalamus, have also been conducted in humans. These studies show that targeted ultrasound stimulation can influence certain pain metrics.

Whether these effects lead to lasting clinical improvement in various chronic pain syndromes requires further investigation.

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Depression and emotion regulation

Brain networks involved in mood and emotion regulation include the prefrontal cortex, amygdala, and cingulate cortex.

Some of these structures are located relatively deep in the brain.

tFUS offers the ability to target these areas for research.

A 2026 systematic review in the Journal of Affective Disorders analyzed eleven human studies on the influence of tFUS on emotion regulation and related symptoms.

Changes in mood, anxiety, and emotional processing were reported in several studies.

The results are promising, but the studies vary significantly in design, stimulation parameters, brain regions investigated, and participants.

The researchers therefore emphasize that larger, well-controlled clinical trials are necessary before reliable conclusions about therapeutic efficacy can be drawn.

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Anxiety disorders and other psychiatric conditions

Research is also being conducted into whether targeted stimulation of brain networks can have a clinically relevant effect on anxiety disorders and other psychiatric conditions.

A 2026 systematic review in Brain and Spine examined the available clinical studies on low-intensity and high-intensity focused ultrasound for psychiatric conditions.

The authors found evidence of potential symptom improvement in selected study groups.

At the same time, they emphasized that the available evidence remains limited due to small study groups, varying protocols, and methodological limitations.

The results support further research, but do not yet provide a basis for considering low-intensity tFUS a generally proven treatment for psychiatric disorders.

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Tinnitus

Tinnitus involves more than just sound processing. Brain networks involved in attention, emotional significance, and awareness can also contribute to the burden of tinnitus.

Because tFUS can target specific brain structures, the technology is an interesting avenue for research into neuromodulation for tinnitus.

However, there is currently insufficient clinical evidence to conclude that low-intensity tFUS is an effective treatment for tinnitus.

Future research must determine which brain regions are relevant, which stimulation parameters are appropriate, and whether any changes in brain activity correlate with a meaningful and lasting reduction in tinnitus symptoms.

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How accurate is tFUS?

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An important technical feature of tFUS is its ability to focus ultrasonic energy into a relatively small area of the brain.

In experimental settings, the focus can reach a scale of millimeters.

However, the actual accuracy depends on several factors, including the equipment used, the frequency of the sound waves, the position of the transducer, and the properties of the skull.

The skull can attenuate, deflect, and distort ultrasonic waves.

Therefore, research is being conducted into how imaging, neuronavigation, and acoustic simulations can help reach the target brain area as accurately as possible.

A 2026 study in Ultrasound in Medicine & Biology , for example, investigated how transducer positioning can be optimized using computer models.

This type of research is important for further improving the technical accuracy and reproducibility of tFUS.

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Is tFUS safe?

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Initial studies in humans suggest that low-intensity tFUS is generally well-tolerated under carefully controlled research conditions.

Published studies have reported side effects such as temporary headaches, dizziness, scalp sensitivity, and discomfort during the procedure.

However, significant questions remain regarding the safety of repeated treatments, optimal intensity, duration of stimulation, and potential long-term effects.

Furthermore, it is important to distinguish between the safety of a specific study protocol and that of other applications using different stimulation parameters.

Safety must therefore be assessed on a case-by-case basis, depending on the equipment used, the stimulation protocol, the individual, and the targeted brain region.

After all, non-invasive does not automatically mean risk-free.

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What does tFUS mean for the future of neuromodulation?

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The development of tFUS opens up new possibilities for research into how brain networks function.

The combination of high spatial precision and the ability to reach deeper brain structures makes this technology particularly scientifically compelling.

Future research will need to demonstrate which applications offer genuine clinical value, how patients can best be selected, and which stimulation protocols are safe and reproducible.

At BRAI3N, we follow these developments based on our conviction that scientific research and clinical care should reinforce one another.

New technologies deserve a place in patient care once their safety, efficacy, and clinical relevance have been sufficiently established.

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tFUS represents an important new research direction in neuromodulation. The possibilities are promising, but scientific rigor remains essential to translate those possibilities into clinical practice responsibly.

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Scientific publications

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1. General mechanism and potential of tFUS

Davidson B, Schmidt FA, Bichsel O, Hajiabadi MM, Lozano AM. (2026). Transcranial Focused Ultrasound: A Transformative Tool for Intracranial Ablation, Drug Delivery, and Neuromodulation. IEEE Reviews in Biomedical Engineering.

https://doi.org/10.1109/RBME.2025.3624970

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2. tFUS for modulating pain networks

Badran BW, Peng X. (2024). Transcranial focused ultrasound (tFUS): a promising noninvasive deep brain stimulation approach for pain. Neuropsychopharmacology, 49, 351–352.

https://doi.org/10.1038/s41386-023-01699-w

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3. tFUS and long-term postoperative pain — animal research

Yang J, Bo H, Lv P, et al. (2026). Targeting the Medial Prefrontal Cortex with Transcranial Focused Ultrasound Alleviates Adolescent Sleep-Deprivation-Induced Persistent Postsurgical Pain in Adulthood. Research, 9, Article 1437.

https://doi.org/10.34133/research.1437

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4. tFUS and emotion regulation — systematic review and quantitative synthesis

Kang Y, Han KM, Ham BJ, Auer DP, Kaiser M, Jung JY. (2026). Transcranial focused ultrasound for emotion regulation: A systematic review and quantitative summary of human studies. Journal of Affective Disorders, 405, 121621.

https://doi.org/10.1016/j.jad.2026.121621

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5. Focused ultrasound stimulation for psychiatric disorders — systematic review

Cervantes-Hernández A, et al. (2026). High-intensity focused ultrasound (HIFU) and low-intensity focused ultrasound (LIFU) as neurosurgical approaches in psychiatry: A systematic review of current clinical evidence. Brain and Spine, 6, 107438.

https://doi.org/10.1016/j.bas.2026.107438

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6. Research into the influence of tFUS on human brain activity

Kosnoff J, et al. (2026). Transcranial focused ultrasound induces source localizable cortical activation in resting state humans when applied concurrently with transcranial electric stimulation. Nature Communications, 17, 2023.

https://doi.org/10.1038/s41467-026-69853-8

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7. Technical optimization of the stimulation site

Gao P, Sun Y, Zhang G, Wang L. (2026). Adaptive Positioning and Targeting Optimization in Transcranial Focused Ultrasound (tFUS): A Numerical Study. Ultrasound in Medicine & Biology, 52, 2866–2875.

https://doi.org/10.1016/j.ultrasmedbio.2026.08.024

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8. Initial clinical exploration for central neuropathic pain

Nunes GA, et al. (2026). Safety and Feasibility of Low-Intensity Transcranial Focused Ultrasound Targeting the Anterior Thalamus: A Pilot Study for Chronic Central Neuropathic Pain. Journal of ECT.

https://doi.org/10.1097/YCT.0000000000001298

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This information describes the current state of scientific research and does not constitute evidence that tFUS is an established or available treatment for all mentioned conditions.

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