Auditory confounds can drive online effects of transcranial ultrasonic stimulation in humans
Transcranial ultrasonic stimulation (TUS) is rapidly emerging as a promising non-invasive neuromodulation technique. TUS is already well-established in animal models, providing foundations to now optimize neuromodulatory efficacy for human applications. Across multiple studies, one promising protoco...
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eLife Sciences Publications Ltd
2024-08-01
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| Online Access: | https://elifesciences.org/articles/88762 |
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| author | Benjamin R Kop Yazan Shamli Oghli Talyta C Grippe Tulika Nandi Judith Lefkes Sjoerd W Meijer Soha Farboud Marwan Engels Michelle Hamani Melissa Null Angela Radetz Umair Hassan Ghazaleh Darmani Andrey Chetverikov Hanneke EM den Ouden Til Ole Bergmann Robert Chen Lennart Verhagen |
| author_facet | Benjamin R Kop Yazan Shamli Oghli Talyta C Grippe Tulika Nandi Judith Lefkes Sjoerd W Meijer Soha Farboud Marwan Engels Michelle Hamani Melissa Null Angela Radetz Umair Hassan Ghazaleh Darmani Andrey Chetverikov Hanneke EM den Ouden Til Ole Bergmann Robert Chen Lennart Verhagen |
| author_sort | Benjamin R Kop |
| collection | DOAJ |
| description | Transcranial ultrasonic stimulation (TUS) is rapidly emerging as a promising non-invasive neuromodulation technique. TUS is already well-established in animal models, providing foundations to now optimize neuromodulatory efficacy for human applications. Across multiple studies, one promising protocol, pulsed at 1000 Hz, has consistently resulted in motor cortical inhibition in humans (Fomenko et al., 2020). At the same time, a parallel research line has highlighted the potentially confounding influence of peripheral auditory stimulation arising from TUS pulsing at audible frequencies. In this study, we disentangle direct neuromodulatory and indirect auditory contributions to motor inhibitory effects of TUS. To this end, we include tightly matched control conditions across four experiments, one preregistered, conducted independently at three institutions. We employed a combined transcranial ultrasonic and magnetic stimulation paradigm, where TMS-elicited motor-evoked potentials (MEPs) served as an index of corticospinal excitability. First, we replicated motor inhibitory effects of TUS but showed through both tight controls and manipulation of stimulation intensity, duration, and auditory masking conditions that this inhibition was driven by peripheral auditory stimulation, not direct neuromodulation. Furthermore, we consider neuromodulation beyond driving overall excitation/inhibition and show preliminary evidence of how TUS might interact with ongoing neural dynamics instead. Primarily, this study highlights the substantial shortcomings in accounting for the auditory confound in prior TUS-TMS work where only a flip-over sham and no active control was used. The field must critically reevaluate previous findings given the demonstrated impact of peripheral confounds. Furthermore, rigorous experimental design via (in)active control conditions is required to make substantiated claims in future TUS studies. Only when direct effects are disentangled from those driven by peripheral confounds can TUS fully realize its potential for research and clinical applications. |
| format | Article |
| id | doaj-art-92f2d3bd6d274cd3b45caea1872d3f5d |
| institution | Kabale University |
| issn | 2050-084X |
| language | English |
| publishDate | 2024-08-01 |
| publisher | eLife Sciences Publications Ltd |
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| series | eLife |
| spelling | doaj-art-92f2d3bd6d274cd3b45caea1872d3f5d2025-02-10T18:04:42ZengeLife Sciences Publications LtdeLife2050-084X2024-08-011210.7554/eLife.88762Auditory confounds can drive online effects of transcranial ultrasonic stimulation in humansBenjamin R Kop0https://orcid.org/0000-0001-7817-5845Yazan Shamli Oghli1Talyta C Grippe2Tulika Nandi3Judith Lefkes4Sjoerd W Meijer5Soha Farboud6Marwan Engels7Michelle Hamani8Melissa Null9Angela Radetz10Umair Hassan11Ghazaleh Darmani12Andrey Chetverikov13Hanneke EM den Ouden14https://orcid.org/0000-0001-7039-5130Til Ole Bergmann15Robert Chen16Lennart Verhagen17https://orcid.org/0000-0003-3207-7929Donders Institute for Brain, Cognition, and Behaviour; Radboud University Nijmegen, Nijmegen, NetherlandsKrembil Research Institute, University Health Network; University of Toronto, Toronto, CanadaKrembil Research Institute, University Health Network; University of Toronto, Toronto, CanadaNeuroimaging Center; Johannes-Gutenberg University Medical Center Mainz, Mainz, GermanyDonders Institute for Brain, Cognition, and Behaviour; Radboud University Nijmegen, Nijmegen, NetherlandsDonders Institute for Brain, Cognition, and Behaviour; Radboud University Nijmegen, Nijmegen, NetherlandsDonders Institute for Brain, Cognition, and Behaviour; Radboud University Nijmegen, Nijmegen, NetherlandsDonders Institute for Brain, Cognition, and Behaviour; Radboud University Nijmegen, Nijmegen, NetherlandsKrembil Research Institute, University Health Network; University of Toronto, Toronto, CanadaNeuroimaging Center; Johannes-Gutenberg University Medical Center Mainz, Mainz, GermanyNeuroimaging Center; Johannes-Gutenberg University Medical Center Mainz, Mainz, GermanyNeuroimaging Center; Johannes-Gutenberg University Medical Center Mainz, Mainz, GermanyKrembil Research Institute, University Health Network; University of Toronto, Toronto, CanadaDonders Institute for Brain, Cognition, and Behaviour; Radboud University Nijmegen, Nijmegen, Netherlands; Department of Psychosocial Science, Faculty of Psychology, University of Bergen, Bergen, NorwayDonders Institute for Brain, Cognition, and Behaviour; Radboud University Nijmegen, Nijmegen, NetherlandsNeuroimaging Center; Johannes-Gutenberg University Medical Center Mainz, Mainz, Germany; Leibniz Institute for Resilience Research Mainz, Mainz, GermanyKrembil Research Institute, University Health Network; University of Toronto, Toronto, CanadaDonders Institute for Brain, Cognition, and Behaviour; Radboud University Nijmegen, Nijmegen, NetherlandsTranscranial ultrasonic stimulation (TUS) is rapidly emerging as a promising non-invasive neuromodulation technique. TUS is already well-established in animal models, providing foundations to now optimize neuromodulatory efficacy for human applications. Across multiple studies, one promising protocol, pulsed at 1000 Hz, has consistently resulted in motor cortical inhibition in humans (Fomenko et al., 2020). At the same time, a parallel research line has highlighted the potentially confounding influence of peripheral auditory stimulation arising from TUS pulsing at audible frequencies. In this study, we disentangle direct neuromodulatory and indirect auditory contributions to motor inhibitory effects of TUS. To this end, we include tightly matched control conditions across four experiments, one preregistered, conducted independently at three institutions. We employed a combined transcranial ultrasonic and magnetic stimulation paradigm, where TMS-elicited motor-evoked potentials (MEPs) served as an index of corticospinal excitability. First, we replicated motor inhibitory effects of TUS but showed through both tight controls and manipulation of stimulation intensity, duration, and auditory masking conditions that this inhibition was driven by peripheral auditory stimulation, not direct neuromodulation. Furthermore, we consider neuromodulation beyond driving overall excitation/inhibition and show preliminary evidence of how TUS might interact with ongoing neural dynamics instead. Primarily, this study highlights the substantial shortcomings in accounting for the auditory confound in prior TUS-TMS work where only a flip-over sham and no active control was used. The field must critically reevaluate previous findings given the demonstrated impact of peripheral confounds. Furthermore, rigorous experimental design via (in)active control conditions is required to make substantiated claims in future TUS studies. Only when direct effects are disentangled from those driven by peripheral confounds can TUS fully realize its potential for research and clinical applications.https://elifesciences.org/articles/88762transcranial ultrasound stimulationTUSauditory confoundneuromodulationexperimental controldesign |
| spellingShingle | Benjamin R Kop Yazan Shamli Oghli Talyta C Grippe Tulika Nandi Judith Lefkes Sjoerd W Meijer Soha Farboud Marwan Engels Michelle Hamani Melissa Null Angela Radetz Umair Hassan Ghazaleh Darmani Andrey Chetverikov Hanneke EM den Ouden Til Ole Bergmann Robert Chen Lennart Verhagen Auditory confounds can drive online effects of transcranial ultrasonic stimulation in humans eLife transcranial ultrasound stimulation TUS auditory confound neuromodulation experimental control design |
| title | Auditory confounds can drive online effects of transcranial ultrasonic stimulation in humans |
| title_full | Auditory confounds can drive online effects of transcranial ultrasonic stimulation in humans |
| title_fullStr | Auditory confounds can drive online effects of transcranial ultrasonic stimulation in humans |
| title_full_unstemmed | Auditory confounds can drive online effects of transcranial ultrasonic stimulation in humans |
| title_short | Auditory confounds can drive online effects of transcranial ultrasonic stimulation in humans |
| title_sort | auditory confounds can drive online effects of transcranial ultrasonic stimulation in humans |
| topic | transcranial ultrasound stimulation TUS auditory confound neuromodulation experimental control design |
| url | https://elifesciences.org/articles/88762 |
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