Transcranial ultrasound stimulation in humans is associated with an auditory confound that can be effectively masked
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Published version
Author(s)
Braun, Verena
Blackmore, Joseph
Cleveland, Robin O
Butler, Christopher R
Type
Journal Article
Abstract
Background
Transcranial ultrasound stimulation (TUS) is emerging as a potentially powerful, non-invasive technique for focal brain stimulation. Recent animal work suggests, however, that TUS effects may be confounded by indirect stimulation of early auditory pathways.
Objective
We aimed to investigate in human participants whether TUS elicits audible sounds and if these can be masked by an audio signal.
Methods
In 18 healthy participants, T1-weighted magnetic resonance brain imaging was acquired for 3D ultrasound simulations to determine optimal transducer placements and source amplitudes. Thermal simulations ensured that temperature rises were <0.5 °C at the target and <3 °C in the skull. To test for non-specific auditory activation, TUS (500 kHz, 300 ms burst, modulated at 1 kHz with 50% duty cycle) was applied to primary visual cortex and participants were asked to distinguish stimulation from non-stimulation trials. EEG was recorded throughout the task. Furthermore, ex-vivo skull experiments tested for the presence of skull vibrations during TUS.
Results
We found that participants can hear sound during TUS and can distinguish between stimulation and non-stimulation trials. This was corroborated by EEG recordings indicating auditory activation associated with TUS. Delivering an audio waveform to participants through earphones while TUS was applied reduced detection rates to chance level and abolished the TUS-induced auditory EEG signal. Ex vivo skull experiments demonstrated that sound is conducted through the skull at the pulse repetition frequency of the ultrasound.
Conclusion
Future studies using TUS in humans need to take this auditory confound into account and mask stimulation appropriately.
Transcranial ultrasound stimulation (TUS) is emerging as a potentially powerful, non-invasive technique for focal brain stimulation. Recent animal work suggests, however, that TUS effects may be confounded by indirect stimulation of early auditory pathways.
Objective
We aimed to investigate in human participants whether TUS elicits audible sounds and if these can be masked by an audio signal.
Methods
In 18 healthy participants, T1-weighted magnetic resonance brain imaging was acquired for 3D ultrasound simulations to determine optimal transducer placements and source amplitudes. Thermal simulations ensured that temperature rises were <0.5 °C at the target and <3 °C in the skull. To test for non-specific auditory activation, TUS (500 kHz, 300 ms burst, modulated at 1 kHz with 50% duty cycle) was applied to primary visual cortex and participants were asked to distinguish stimulation from non-stimulation trials. EEG was recorded throughout the task. Furthermore, ex-vivo skull experiments tested for the presence of skull vibrations during TUS.
Results
We found that participants can hear sound during TUS and can distinguish between stimulation and non-stimulation trials. This was corroborated by EEG recordings indicating auditory activation associated with TUS. Delivering an audio waveform to participants through earphones while TUS was applied reduced detection rates to chance level and abolished the TUS-induced auditory EEG signal. Ex vivo skull experiments demonstrated that sound is conducted through the skull at the pulse repetition frequency of the ultrasound.
Conclusion
Future studies using TUS in humans need to take this auditory confound into account and mask stimulation appropriately.
Date Issued
2020-11-01
Date Acceptance
2020-08-27
Citation
Brain Stimulation, 2020, 13 (6), pp.1527-1534
ISSN
1876-4754
Publisher
Elsevier
Start Page
1527
End Page
1534
Journal / Book Title
Brain Stimulation
Volume
13
Issue
6
Copyright Statement
© 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
License URL
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000597945200010&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Clinical Neurology
Neurosciences
Neurosciences & Neurology
Transcranial ultrasound stimulation (TUS)
EEG
Human auditory perception
Neuromodulation
Non-invasive
Publication Status
Published
Date Publish Online
2020-09-04
