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Transcranial focused ultrasound-mediated neurochemical and functional connectivity changes in deep cortical regions in humans

View ORCID ProfileSiti N. Yaakub, Tristan A. White, Jamie Roberts, View ORCID ProfileLennart Verhagen, View ORCID ProfileCharlotte J. Stagg, Stephen Hall, View ORCID ProfileElsa F. Fouragnan
doi: https://doi.org/10.1101/2023.01.20.524869
Siti N. Yaakub
1School of Psychology, Faculty of Health, University of Plymouth, Plymouth, United Kingdom
2Brain Research and Imaging Centre, Faculty of Health, University of Plymouth, Plymouth, United Kingdom
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Tristan A. White
1School of Psychology, Faculty of Health, University of Plymouth, Plymouth, United Kingdom
2Brain Research and Imaging Centre, Faculty of Health, University of Plymouth, Plymouth, United Kingdom
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Jamie Roberts
3Department of Clinical Measurement and Innovation, University Hospitals Plymouth NHS Trust, Plymouth, United Kingdom
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Lennart Verhagen
4Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Nijmegen, Netherlands
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  • ORCID record for Lennart Verhagen
Charlotte J. Stagg
5Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
6MRC Brain Network Dynamics Unit, University of Oxford, Oxford, United Kingdom
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Stephen Hall
1School of Psychology, Faculty of Health, University of Plymouth, Plymouth, United Kingdom
2Brain Research and Imaging Centre, Faculty of Health, University of Plymouth, Plymouth, United Kingdom
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Elsa F. Fouragnan
1School of Psychology, Faculty of Health, University of Plymouth, Plymouth, United Kingdom
2Brain Research and Imaging Centre, Faculty of Health, University of Plymouth, Plymouth, United Kingdom
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  • ORCID record for Elsa F. Fouragnan
  • For correspondence: elsa.fouragnan@plymouth.ac.uk
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Abstract

Low-intensity transcranial ultrasound stimulation (TUS) is an emerging non-invasive technique for focally modulating human brain function. The mechanisms and neurochemical substrates underlying TUS neuromodulation in humans and how these relate to excitation and inhibition are still poorly understood. In 24 healthy controls, we separately stimulated two deep cortical regions and investigated the effects of theta-burst TUS, a protocol shown to increase corticospinal excitability, on the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and functional connectivity. We show for the first time in humans that theta-burst TUS selectively reduces GABA levels in the posterior cingulate, but not the dorsal anterior cingulate cortex. Functional connectivity increased following TUS in both regions. Our findings suggest that TUS changes overall excitability by reducing GABAergic inhibition, that changes in TUS-mediated neuroplasticity last at least 50 minutes after stimulation, and that these effects may be state-dependent – a mechanism increasingly recognized to influence the brain’s response to neuromodulation.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://osf.io/bcf4v

  • https://osf.io/rp5g4/

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted January 20, 2023.
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Transcranial focused ultrasound-mediated neurochemical and functional connectivity changes in deep cortical regions in humans
Siti N. Yaakub, Tristan A. White, Jamie Roberts, Lennart Verhagen, Charlotte J. Stagg, Stephen Hall, Elsa F. Fouragnan
bioRxiv 2023.01.20.524869; doi: https://doi.org/10.1101/2023.01.20.524869
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Transcranial focused ultrasound-mediated neurochemical and functional connectivity changes in deep cortical regions in humans
Siti N. Yaakub, Tristan A. White, Jamie Roberts, Lennart Verhagen, Charlotte J. Stagg, Stephen Hall, Elsa F. Fouragnan
bioRxiv 2023.01.20.524869; doi: https://doi.org/10.1101/2023.01.20.524869

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