Parameter optimisation for mitigating somatosensory confounds during transcranial ultrasonic stimulation

Background: Transcranial ultrasonic stimulation (TUS) redefines what is possible with non-invasive neuromodulation by offering unparalleled spatial precision and flexible targeting capabilities. However, peripheral confounds pose a significant challenge to reliably implementing this technology. Whil...

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Main Authors: Benjamin R. Kop, Linda de Jong, Butts Pauly Kim, Hanneke E.M. den Ouden, Lennart Verhagen
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:Brain Stimulation
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Online Access:http://www.sciencedirect.com/science/article/pii/S1935861X25002608
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author Benjamin R. Kop
Linda de Jong
Butts Pauly Kim
Hanneke E.M. den Ouden
Lennart Verhagen
author_facet Benjamin R. Kop
Linda de Jong
Butts Pauly Kim
Hanneke E.M. den Ouden
Lennart Verhagen
author_sort Benjamin R. Kop
collection DOAJ
description Background: Transcranial ultrasonic stimulation (TUS) redefines what is possible with non-invasive neuromodulation by offering unparalleled spatial precision and flexible targeting capabilities. However, peripheral confounds pose a significant challenge to reliably implementing this technology. While auditory confounds during TUS have been studied extensively, the somatosensory confound has been overlooked thus far. It will become increasingly vital to quantify and manage this confound as the field shifts towards higher doses, more compact stimulation devices, and more frequent stimulation through the temples where co-stimulation is more pronounced. Methods: Here, we provide a systematic characterisation of somatosensory co-stimulation during TUS. We also identify the conditions under which this confound can be mitigated most effectively by mapping the confound-parameter space. Specifically, we investigate dose-response effects, pulse shaping characteristics, and transducer-specific parameters. Results: We demonstrate that somatosensory confounds can be mitigated by avoiding near-field intensity peaks in the scalp, spreading energy across a greater area of the scalp, ramping the pulse envelope, and delivering equivalent doses via longer, lower-intensity pulses rather than shorter, higher-intensity pulses. Additionally, higher pulse repetition frequencies and fundamental frequencies reduce somatosensory effects. Through our systematic mapping of the parameter space, we also find preliminary evidence that particle displacement (strain) may be a primary biophysical driving force behind peripheral somatosensory co-stimulation. Conclusion: This study provides actionable strategies to minimise somatosensory confounds, which will support the thorough experimental control required to unlock the full potential of TUS for scientific research and clinical interventions.
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spelling doaj-art-b59a89735d534e9490753384d69cc63f2025-07-05T04:47:01ZengElsevierBrain Stimulation1935-861X2025-07-0118412241236Parameter optimisation for mitigating somatosensory confounds during transcranial ultrasonic stimulationBenjamin R. Kop0Linda de Jong1Butts Pauly Kim2Hanneke E.M. den Ouden3Lennart Verhagen4Donders Institute for Brain, Cognition, and Behaviour, Radboud University, Thomas van Aquinostraat 4, 6525 GD, Nijmegen, the Netherlands; Corresponding author.Donders Institute for Brain, Cognition, and Behaviour, Radboud University, Thomas van Aquinostraat 4, 6525 GD, Nijmegen, the NetherlandsDepartment of Radiology, Stanford University, 300 Pasteur Drive, Stanford, CA, USADonders Institute for Brain, Cognition, and Behaviour, Radboud University, Thomas van Aquinostraat 4, 6525 GD, Nijmegen, the NetherlandsDonders Institute for Brain, Cognition, and Behaviour, Radboud University, Thomas van Aquinostraat 4, 6525 GD, Nijmegen, the NetherlandsBackground: Transcranial ultrasonic stimulation (TUS) redefines what is possible with non-invasive neuromodulation by offering unparalleled spatial precision and flexible targeting capabilities. However, peripheral confounds pose a significant challenge to reliably implementing this technology. While auditory confounds during TUS have been studied extensively, the somatosensory confound has been overlooked thus far. It will become increasingly vital to quantify and manage this confound as the field shifts towards higher doses, more compact stimulation devices, and more frequent stimulation through the temples where co-stimulation is more pronounced. Methods: Here, we provide a systematic characterisation of somatosensory co-stimulation during TUS. We also identify the conditions under which this confound can be mitigated most effectively by mapping the confound-parameter space. Specifically, we investigate dose-response effects, pulse shaping characteristics, and transducer-specific parameters. Results: We demonstrate that somatosensory confounds can be mitigated by avoiding near-field intensity peaks in the scalp, spreading energy across a greater area of the scalp, ramping the pulse envelope, and delivering equivalent doses via longer, lower-intensity pulses rather than shorter, higher-intensity pulses. Additionally, higher pulse repetition frequencies and fundamental frequencies reduce somatosensory effects. Through our systematic mapping of the parameter space, we also find preliminary evidence that particle displacement (strain) may be a primary biophysical driving force behind peripheral somatosensory co-stimulation. Conclusion: This study provides actionable strategies to minimise somatosensory confounds, which will support the thorough experimental control required to unlock the full potential of TUS for scientific research and clinical interventions.http://www.sciencedirect.com/science/article/pii/S1935861X25002608Transcranial ultrasonic stimulation (TUS)NeuromodulationPeripheral confoundsSomatosensory confoundsExperimental design & controlPeripheral nervous system
spellingShingle Benjamin R. Kop
Linda de Jong
Butts Pauly Kim
Hanneke E.M. den Ouden
Lennart Verhagen
Parameter optimisation for mitigating somatosensory confounds during transcranial ultrasonic stimulation
Brain Stimulation
Transcranial ultrasonic stimulation (TUS)
Neuromodulation
Peripheral confounds
Somatosensory confounds
Experimental design & control
Peripheral nervous system
title Parameter optimisation for mitigating somatosensory confounds during transcranial ultrasonic stimulation
title_full Parameter optimisation for mitigating somatosensory confounds during transcranial ultrasonic stimulation
title_fullStr Parameter optimisation for mitigating somatosensory confounds during transcranial ultrasonic stimulation
title_full_unstemmed Parameter optimisation for mitigating somatosensory confounds during transcranial ultrasonic stimulation
title_short Parameter optimisation for mitigating somatosensory confounds during transcranial ultrasonic stimulation
title_sort parameter optimisation for mitigating somatosensory confounds during transcranial ultrasonic stimulation
topic Transcranial ultrasonic stimulation (TUS)
Neuromodulation
Peripheral confounds
Somatosensory confounds
Experimental design & control
Peripheral nervous system
url http://www.sciencedirect.com/science/article/pii/S1935861X25002608
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