Lemaire Théo, Vicari Elena, Neufeld Esra, Kuster Niels, Micera Silvestro
Bertarelli Foundation Chair in Translational Neuroengineering, Center for Neuroprosthetics and Institute of Bioengineering, School of Engineering, École Polytechnique Fédérale de Lausanne (EPFL), 1202 Lausanne, Switzerland.
Biorobotics Institute, Scuola Superiore Sant'Anna (SSSA), 56127 Pisa, Italy.
iScience. 2021 Sep 6;24(9):103085. doi: 10.1016/j.isci.2021.103085. eCollection 2021 Sep 24.
Low-Intensity Focused Ultrasound Stimulation (LIFUS) holds promise for the remote modulation of neural activity, but an incomplete mechanistic characterization hinders its clinical maturation. Here we developed a computational framework to model intramembrane cavitation (a candidate mechanism) in multi-compartment, morphologically structured neuron models, and used it to investigate ultrasound neuromodulation of peripheral nerves. We predict that by engaging membrane mechanoelectrical coupling, LIFUS exploits fiber-specific differences in membrane conductance and capacitance to selectively recruit myelinated and/or unmyelinated axons in distinct parametric subspaces, allowing to modulate their activity concurrently and independently over physiologically relevant spiking frequency ranges. These theoretical results consistently explain recent empirical findings and suggest that LIFUS can simultaneously, yet selectively, engage different neural pathways, opening up opportunities for peripheral neuromodulation currently not addressable by electrical stimulation. More generally, our framework is readily applicable to other neural targets to establish application-specific LIFUS protocols.
低强度聚焦超声刺激（LIFUS）有望实现神经活动的远程调节，但对其机制的不完全表征阻碍了其临床成熟。在此，我们开发了一个计算框架，用于在多室、形态学结构的神经元模型中模拟膜内空化（一种候选机制），并利用它来研究外周神经的超声神经调节。我们预测，通过参与膜机械电耦合，LIFUS利用膜电导和电容中纤维特异性差异，在不同的参数子空间中选择性地募集有髓和/或无髓轴突，从而在生理相关的放电频率范围内同时且独立地调节它们的活动。这些理论结果一致地解释了最近的实验发现，并表明LIFUS可以同时但选择性地激活不同的神经通路，为目前电刺激无法解决的外周神经调节开辟了机会。更一般地说，我们的框架很容易应用于其他神经靶点，以建立特定应用的LIFUS方案。
