A Framework for Low-Intensity Low-Frequency Ultrasound Neuromodulation Sonication Parameter Identification from Micromechanical Flexoelectricity Modelling.

Abstract

Low-intensity, low-frequency ultrasound (LILFU) has recently emerged as a promising technique to modulate non-invasively nerve activities at lower cost than other traditional and more-invasive neuromodulation methods. However, there is currently no consensus on the optimum sonication parameters to be used in LILFU applications, and most of the accepted ranges have arisen from trial-and-error approaches. Here we utilise a recently proposed micromechanics model of membrane flexoelectricity, a potential candidate for neuromodulation, and simulate action potentials/membrane polarisation triggered by acoustic pulses of different pulse frequencies, pulse magnitudes and duty cycles. Results reveal that, at constant duty cycles, increasing the transmit frequency increases the thresholds of both the pulse magnitude and the elastic energy rate density required to mechanically trigger an action potential, whereas at constant frequencies, increasing the duty cycle reduces both. The influence of transmit frequency is weakened at lower duty cycles. Our simulation results offer some guidance on the selections of sonication parameters used in LILFU for neurologic disorder treatments in the context of the flexoelectricity hypothesis.