Can ionic concentration changes due to mechanical deformation be responsible for the neurostimulation caused by focused ultrasound? A simulation study

Objective. Ultrasound stimulation is an emerging neuromodulation technique, for which the exact mechanism of action is still unknown. Despite the number of hypotheses such as mechanosensitive ion channels and intermembrane cavitation, they fail to explain all of the observed experimental effects. Here we are investigating the ionic concentration change as a prime mechanism for the neurostimulation by the ultrasound. Approach. We derive the direct analytical relationship between the mechanical deformations in the tissue and the electric boundary conditions for the cable theory equations and solve them for two types of neuronal axon models: Hodgkin-Huxley and C-fibre. We detect the activation thresholds for a variety of ultrasound stimulation cases including continuous and pulsed ultrasound and estimate the mechanical deformations required for reaching the thresholds and generating action potentials (APs). Main results. We note that the proposed mechanism strongly depends on the mechanical properties of the neural tissues, which at the moment cannot be located in literature with the required certainty. We conclude that given certain common linear assumptions, this mechanism alone cannot cause significant effects and be responsible for neurostimulation. However, we also conclude that if the lower estimation of mechanical properties of neural tissues in literature is true, or if the normal cavitation occurs during the ultrasound stimulation, the proposed mechanism can be a prime cause for the generation of APs. Significance. The approach allows prediction and modelling of most observed experimental effects, including the probabilistic ones, without the need for any extra physical effects or additional parameters.

Automated summary

The study investigates the ionic concentration change as a prime mechanism for neurostimulation by ultrasound. By deriving the analytical relationship between tissue mechanical deformations and electric boundary conditions, the study explores the activation thresholds and generation of action potentials in neuronal axon models. The proposed mechanism may be a prime cause for generating action potentials if certain mechanical properties of neural tissues are accurate or cavitation occurs during ultrasound stimulation.