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

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.

A modular strategy for next-generation upper-limb sensory-motor neuroprostheses

“…In the long term-term more-effective and natural movement restoration could be achieved by stimulating the CNS or PNS explanting other non-electrical approaches for neuromodulation, such as optogenetics [102][103][104] or ultrasounds. 105,106 Indeed, preliminary results seem to indicate that these techniques could reduce the ''inverse recruitment problem'' (reducing the issue of the quick onset of fatigue). Moreover, in this way, it could be possible to achieve more-selective muscular recruitment and neural blocking, which is very important for several applications.…”

Improved alpha-beta power reduction via combined Electrical and Ultrasonic stimulation in a Parkinsonian Cortex-Basal Ganglia-Thalamus Computational Model

“…As future work, we intend to apply SECONIC to morphologically realistic models, allowing us to investigate computationally the spatial aspects of UNMOD. In this context, a recent computational study of Lemaire et al (2020) investigated ultrasonic neuromodulation by intramembrane cavitation in multi-compartmental myelinated and unmyelinated axons with the SONIC-framework [79]. Here, spatially-extended multicompartmental neuron models could be integrated within the point neuronal network (as done in [58], for a cortical multi-compartmental cell) and coupled with finite-element and finite-difference time-domain simulations of the electric and ultrasonic field, respectively.…”