MorphoSONIC: A morphologically structured intramembrane cavitation model reveals fiber-specific neuromodulation by ultrasound

Abstract

Summary 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.

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 investigated UNMOD by intramembrane cavitation in multicompartmental myelinated and unmyelinated axons with the SONIC-framework [85]. Here, spatiallyextended multi-compartmental neuron models could be integrated within the point neuronal network (as done in [65], for a cortical multi-compartmental cell) and coupled with finite-element and finite-difference time-domain simulations of the electric and ultrasonic field, respectively.…”

Modeling ultrasound modulation of neural function in a single cell

“…Though computationally exhaustive, the interplay between these two parts allows the prediction of the neural response to ultrasound sonication. The SONIC model (multiscale optimized neuronal intramembrane cavitation model), developed by Lemaire et al [ [43] , [44] , [45] , 44 ], overcomes the computational difficulties and rigidity of the NICE model, allowing for enhanced exploration of the influence of multiple LIFUS parameters on the neural response. These models focus on the cavitation mode of action of ultrasound-tissue interaction and ignore other mechanisms by which ultrasonic waves might induce a neural response, including ion channel mechano-sensitivity [ [45] , [46] , [47] ] and direct and reverse flexoelectricity [ 48 ].…”