TUS
Transcranial Ultrasound Stimulation

What is transcranial ultrasound stimulation?

Transcranial ultrasound stimulation (TUS), also known as Transcranial Focused Ultrasound Stimulation (tFUS), Focused Ultrasound Stimulation (FUS), Focused Ultrasound Neuromodulation (FUN) and Low-Intensity Focused Ultrasound Stimulation (LIFUS), is a new and exciting means of non-invasively modulating neural circuits in the intact human brain. Transcranial-focused ultrasound neuromodulation offers greater spatial resolution and depth of stimulation than is possible with transcranial magnetic stimulation (TMS) or transcranial electrical stimulation (tES).

Why is TUS more accurate than other methods of non-invasive brain stimulation?

Both tES and TMS are inherently limited in the accuracy and depth of the stimulation that they can apply. When applying transcranial electrical stimulation, for instance, the current is 'shunted' by the skull, meaning that only a very small amount of the total current applied by the stimulator actually reaches the desired site in the cortex.

And while TMS does offer the ability to reveal the chronometry of neural processes with a reasonable degree of spatial resolution, it also suffers from a depth vs accuracy tradeoff whereby stimulating at greater depths in the brain necessitates a reduction in spatial resolution.

Transcranial-focused ultrasound neuromodulation, however, offers a new means of modulating neural circuits by using acoustic mechanisms.

TUS generates an acoustic wave via piezoelectricity - a technique in which electricity flows through a crystal, causing vibrations - with the energy generated by these vibrations being subsequently released through the ultrasound transducer.

The shape of the TUS transducer enables this acoustic energy to be acutely focused on one point space, allowing the acoustic wave to be focused at unprecedented depths below the cortical surface with no loss of spatial resolution.

Applications and Effects of TUS

Transcranial-focused ultrasound's ability to accurately target sites beneath the cortical surface has enabled new sites of interest within the brain to become eligible candidates for non-invasive brain stimulation research.

In one real-world example, TUS has enabled the causal functional relevance of the anterior cingulate cortex (ACC), the thalamus and the amygdala, to be investigated. Such investigations have revealed that the ACC is involved in representing the interval value of choices that have not been made immediately, but could be made in the future and whether these representations were used to select a different choice in the future.

TUS Depth of Stimulation

In addition, another study applying TUS for 40 seconds found an effect that reduced the ACC’s connectivity pattern with interconnected regions, lasting for approximately one hour after the application of stimulation. Critically, the spatial distribution of the effects measured by functional magnetic resonance imaging (fMRI) corresponded to the points in space where the acoustic wave was estimated to be greatest on computed tomography (CT) scans.

The effects of TUS have also been observed during electroencephalography (EEG) when focused ultrasound neuromodulation is estimated to have an acoustic focus on the position of the ventral-posterior lateral (VPL) nucleus of the thalamus. A speciļ¬c component of EEG — the P14 — is sensitive to the VPL when the median nerve is stimulated. When Transcranial Ultrasound Stimulation was applied to the thalamus, the amplitude of the P14 was reduced: consistent with the theory that TUS can stimulate sites deep beneath the cortical surface, with effects that can be measured non-invasively from the scalp.

Is transcranial ultrasound stimulation safe?

As with all non-invasive brain stimulation methods, transcranial ultrasound stimulation (TUS) does have a small potential risk of adverse reactions in subjects. A thorough exploration of all of the potential side effects of TUS can be found on our TUS Safety page.

Glossary of Terms

Measure Acronym Description Relevance
Spatial-peak pulse-average intensity Isppa At the spatial peak of intensity, the average intensity during the pulse on-time. Mechanical bioeffects
Spatial-peak temporal-average intensity Ispta At the spatial peak of intensity, the average intensity during a temporal window (e.g., across a burst; across the whole experiment). Thermal bioeffects
Thermal dose in cumulative equivalent minutes CEM43 This measure accounts for both temperature rise and length of stimulation. Thermal bioeffects
Thermal index TI Represents the acoustic power in relation to the power needed to heat the medium by 1°C. Thermal bioeffects
Thermal index for cranial bone TIC An adjusted measure of TI for when the transducer is proximal to the skull. Thermal bioeffects
Mechanical index MI Reflects the probability of acoustic cavitation. Mechanical bioeffects
Pressure (peak instantaneous) p Peak instantaneous pressure. Mechanical bioeffects

 

What is Transcranial Focused Ultrasound Stimulation?

Dr Lennart Verhagen (Donders Institute) provides a clear introduction to TUS techniques in this free webinar. 

An Introduction to the Physics of Transcranial Ultrasound Stimulation

In this Brainbox Initiative webinar, Kyle Morrison of Sonic Concepts, Inc. explores the physics behind TUS.

  1. Non-invasive transcranial ultrasound stimulation for neuromodulation. G. Darmani, T.O. Bergmann, K. Butts Pauly, C.F.Caskey, L. de Lecea, A. Fomenko, E. Fouragnan, W. Legon, K.R. Murphy, T. Nandi, M.A. Phipps, G. Pinto, H. Ramezanpour, J. Sallet, S.N. Yaakub, S. S. Yoop, R.Chen. Clinical Neurophysiology. March 2022
  2. The Brain Electrophysiological Recording and STimulation (BEST) toolbox. Umair Hassan, Stephen Pillen, Christoph Zrenner, Til Ole Bergmann. Brain Stimulation. November 2021
  3. Activation and disruption of a neural mechanism for novel choice in monkeys. Bongioanni, A., Folloni, D., Verhagen, L., Sallet, J., Klein-Flügge, M. C., & Rushworth, M. F. Nature. 2021
  4. Transcranial focused ultrasound generates skull-conducted shear waves: Computational model and implications for neuromodulation. Salahshoor, H., Shapiro, M. G., & Ortiz, M.. Applied Physics Letters. April 2020
  5. MRI monitoring of temperature and displacement for transcranial focus ultrasound applications. Ozenne, V., Constans, C., Bour, P., Santin, M. D., Valabrègue, R., Ahnine, H., ... & Quesson, B.. NeuroImage. January 2020
  6. Systematic examination of low-intensity ultrasound parameters on human motor cortex excitability and behavior. Fomenko, A., Chen, K. H. S., Nankoo, J. F., Saravanamuttu, J., Wang, Y., El-Baba, M., ... & Chen, R.. eLife. 2020
  7. The macaque anterior cingulate cortex translates counterfactual choice value into actual behavioural change.. Fouragnan E F., Chau B H K., Folloni D., Kolling N., Verhagen L., Klein-Flügge M., Tankelevitch L., Papageorgiou G K., Aubry J., Sallet J., Rushworth M.. Nature Neuroscience, 22.. (April 2019), pp. 797-808.
  8. Manipulation of subcortical and deep cortical activity in the primate brain using transcranial focused ultrasound stimulation. Folloni, D., Verhagen, L., Mars, R. B., Fouragnan, E., Constans, C., Aubry, J. F., ... & Sallet, J. Neuron. March 2019
  9. Offline impact of transcranial focused ultrasound on cortical activation in primates.. Verhagen L., Gallea C., Folloni D., Constans C., Jensen D E A., Ahnine H., Roumazeilles L., Santin M., Ahmed B., Lehericy S., Klein-Flügge M C., Krug K., Mars B R., Rushworth M F S, Pouget P, Aubry J., Sallet J.. eLife.. (February 2019).
  10. A basal forebrain-cingulate circuit in macaques decides it is time to act. Khalighinejad, N., Bongioanni, A., Verhagen, L., Folloni, D., Attali, D., Aubry, J. F., ... & Rushworth, M. F. Neuron. 2019
  11. Offline impact of transcranial focused
    ultrasound on cortical activation in
    primates.     Verhagen L., Gallea C., Folloni D., Constans C., Jensen D E A., Ahnine H., Roumazeilles L., Santin M., Ahmed B., Lehericy S., Klein-Flügge M C., Krug K., Mars B R., Rushworth M F S, Pouget P, Aubry J., Sallet J.. eLife. 2019
  12. Neuromodulation with single-element transcranial focused ultrasound in human thalmus.. Legon W., Ai L., Bansal P., Mueller J K.. Human Brain Mapping, 39.. (May 2018), pp. 1995 - 2006.
  13. Noninvasive neuromodulation and thalamic mapping with low-intensity focused ultrasound. Dallapiazza, R. F., Timbie, K. F., Holmberg, S., Gatesman, J., Lopes, M. B., Price, R. J., ... & Elias, W. J. Journal of Neurosurgery. March 2018
  14. Transcranial focused ultrasound neuromodulation of the human primary motor cortex. Legon, W., Bansal, P., Tyshynsky, R., Ai, L., & Mueller, J. K.. Scientific Reports. 2018
  15. Transcranial ultrasonic stimulation modulates single-neuron discharge in macaques performing an antisaccade task. Wattiez, N., Constans, C., Deffieux, T., Daye, P. M., Tanter, M., Aubry, J. F., & Pouget, P.. Brain Stimulation. December 2017
  16. Non-invasive transmission of sensorimotor information in humans using an EEG/focused ultrasound brain-to-brain interface.. Lee, W., Kim, S., Kim, B., Lee, C., Chung, Y. A., Kim, L., & Yoo, S. S.. PloS One. June 2017
  17. Lee, W., Kim, H., Jung, Y., Song, I. U., Chung, Y. A., & Yoo, S. S.. Image-guided transcranial focused ultrasound stimulates human primary somatosensory cortex. Scientific Reports. 2015
  18. Transcranial focused ultrasound modulates intrinsic and evoked EEG dynamics. Mueller, J., Legon, W., Opitz, A., Sato, T. F., & Tyler, W. J.. Brain Stimulation. September 2014
  19. Coil design considerations for deep transcranial magnetic stimulation.. Deng Z., Lisanby S H., Peterchev A V.. Clinical Neurophysiology, 125.. (June 2014), pp. 1202-1212.
  20. Transcranial focused ultrasound modulates the activity of primary somatosensory cortex in humans. Legon, W., Sato, T. F., Opitz, A., Mueller, J., Barbour, A., Williams, A., & Tyler, W. J.. Nature Neuroscience. 2014
  21. Low-intensity focused ultrasound modulates monkey visuomotor behavior. Deffieux, T., Younan, Y., Wattiez, N., Tanter, M., Pouget, P., & Aubry, J. F.. Current Biology. 2013
  22. Somatosensory evoked potentials from the thalamic sensory relay nucleus (VPS) in humans: correlations with short latency somatosensory evoked potentials recorded at the scalp.. Katayama Y., Tsubokawa T.. Electroencephalography and Clinical Neurophysiology/Evoked Potentials Section, 68.. (May 1987), pp. 187-201.

Associated Products

The following products from our catalogue are associated with this technique. To find out more about these supported devices, follow the links below or get in touch via email or phone.

TUS

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