What is transcranial focused ultrasound stimulation?
Transcranial ultrasound stimulation (commonly abbreviated to TUS, tFUS, or FUN) 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.
In addition, another study applying tFUS 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 tFUS have also been observed during electroencephalography (EEG) when focused ultrasound neuromodulation is estimated to have an acoustic focus on the position of the ventro-posterior lateral (VPL) nucleus of the thalamus. A speciﬁc component of EEG — the P14 — is sensitive to the VPL when the median nerve is stimulated. When tFUS was applied to the thalamus, the amplitude of the P14 was reduced: consistent with the theory that tFUS can stimulate sites deep beneath the cortical surface, with effects that can be measured non-invasively from the scalp.
Is transcranial-focused ultrasound stimulation safe?
As with all non-invasive brain stimulation methods, transcranial-focused 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
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 Focused Ultrasound
In this Brainbox Initiative webinar, Kyle Morrison of Sonic Concepts, Inc. explores the physics behind TUS.
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- The Brain Electrophysiological Recording and STimulation (BEST) toolbox. Umair Hassan, Stephen Pillen, Christoph Zrenner, Til Ole Bergmann. Brain Stimulation. November 2021
- 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
- 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
- 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
- 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
- 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.
- 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
- 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).
- 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
- 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
- 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.
- 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
- Transcranial focused ultrasound neuromodulation of the human primary motor cortex. Legon, W., Bansal, P., Tyshynsky, R., Ai, L., & Mueller, J. K.. Scientific Reports. 2018
- 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
- 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
- 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
- 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
- Coil design considerations for deep transcranial magnetic stimulation.. Deng Z., Lisanby S H., Peterchev A V.. Clinical Neurophysiology, 125.. (June 2014), pp. 1202-1212.
- 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
- Low-intensity focused ultrasound modulates monkey visuomotor behavior. Deffieux, T., Younan, Y., Wattiez, N., Tanter, M., Pouget, P., & Aubry, J. F.. Current Biology. 2013
- 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.
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