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Mechanistic modeling suggests that low-intensity focused ultrasound can selectively recruit myelinated or unmyelinated nerve fibers

View ORCID ProfileThéo Lemaire, Elena Vicari, View ORCID ProfileEsra Neufeld, View ORCID ProfileNiels Kuster, View ORCID ProfileSilvestro Micera
doi: https://doi.org/10.1101/2020.11.19.390070
Théo Lemaire
1Translational Neural Engineering Laboratory, Center for Neuroprosthetics and Institute of Bioengineering, School of Engineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
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Elena Vicari
1Translational Neural Engineering Laboratory, Center for Neuroprosthetics and Institute of Bioengineering, School of Engineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
2The Biorobotics Institute, Scuola Superiore Sant’Anna (SSSA), Pisa, Italy
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Esra Neufeld
3Foundation for Research on Information Technologies in Society (IT’IS), Zurich, Switzerland
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Niels Kuster
3Foundation for Research on Information Technologies in Society (IT’IS), Zurich, Switzerland
4Department of Information Technology and Electrical Engineering, Swiss Federal Institute of Technology (ETH) Zurich, Zurich, Switzerland
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Silvestro Micera
1Translational Neural Engineering Laboratory, Center for Neuroprosthetics and Institute of Bioengineering, School of Engineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
2The Biorobotics Institute, Scuola Superiore Sant’Anna (SSSA), Pisa, Italy
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  • For correspondence: silvestro.micera@epfl.ch
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Abstract

Low-Intensity Focused Ultrasound Stimulation (LIFUS) holds promise for the remote modulation of neuronal activity, but an incomplete mechanistic characterization hinders its clinical maturation. Here, we developed a computational framework to model intramembrane cavitation in multi-compartmental, morphologically-realistic neuronal representations, and used it to investigate ultrasound neuromodulation of peripheral nerves by spatially-varying pressure fields. Our findings show that LIFUS offers distinct parametric sub-spaces to selectively recruit myelinated or unmyelinated axons and modulate their spiking activity over physiologically relevant regimes and within safe exposure limits. This singular feature, explained by fiber-specific differences in membrane electromechanical coupling, consistently explains recent empirical findings and suggests that LIFUS can preferentially target nociceptive and sensory fibers to enable peripheral therapeutic applications not addressable by electric stimulation. These results open up new opportunities for the development of more selective and effective peripheral neuroprostheses. Our framework can be readily applied to other neural targets to establish application-specific LIFUS protocols.

Competing Interest Statement

The authors have declared no competing interest.

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-NC-ND 4.0 International license.
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Posted November 20, 2020.
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Mechanistic modeling suggests that low-intensity focused ultrasound can selectively recruit myelinated or unmyelinated nerve fibers
Théo Lemaire, Elena Vicari, Esra Neufeld, Niels Kuster, Silvestro Micera
bioRxiv 2020.11.19.390070; doi: https://doi.org/10.1101/2020.11.19.390070
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Mechanistic modeling suggests that low-intensity focused ultrasound can selectively recruit myelinated or unmyelinated nerve fibers
Théo Lemaire, Elena Vicari, Esra Neufeld, Niels Kuster, Silvestro Micera
bioRxiv 2020.11.19.390070; doi: https://doi.org/10.1101/2020.11.19.390070

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