Ultrasound Neuromodulation

Focused Ultrasound Stimulation (FUS) is a non-invasive therapeutic tool with great potential, widely used on humans for ablation therapies and diagnostic imaging. It has recently emerged as a promising technology to achieve reliable, selective and noninvasive neuromodulation of various targets of the central nervous system of rodents, non-human primates and humans (King et al., 2013; Legon et al., 2014). A myriad of applications can therefore be envisaged in which US would replace the standard and invasive electrical stimulation. However, in order for FUS to become a reliable neuromodulation technology, we need a deeper understanding of the fundamental mechanism(s) by which ultrasonic waves can modulate neural activity.

We wish to assess if/how FUS can be applied for neuromodulation of the peripheral nervous system (and especially in autonomic pathways) where it could find a number of useful applications. To do so, we are currently developing a modeling framework to predict how low-intensity ultrasonic waves can modulate the activity of different types of peripheral fibers. This framework is based on the neuronal intramembrane cavitation excitation (NICE) theory recently proposed by Plaksin et al., that provides accurate predictions of central nervous system (CNS) neurons excitation for a wide range of sonication conditions.

First, we have developed a multi-Scale Optimized Neuronal Intramembrane Cavitation (SONIC) model (Lemaire et al., 2019) allowing to simulate the responses of various point-neuron models to ultrasound stimulation in a computationally efficient and interpretable manner. We also developed an associated web app:

SONIC web app

Building on this novel paradigm, we have recently developed a computational framework allowing to simulate intramembrane cavitation in multi-compartmental neuronal representations, thereby expanding model predictions to the morphological scale. With this framework, called morphoSONIC, we investigated the responses myelinated and unmyelinated peripheral axons to various acoustic pressure fields and found that FUS stimuli could be fine-tuned in order to selectively recruit myelinated and/or unmyelinated nerve fibers (Lemaire et al., 2020). These predictions are in qualitative agreement with recent empirical observations, and suggest that FUS can preferentially target nociceptive and sensory fibers, opening up new opportunities for peripheral therapeutic applications currently not addressable by electric stimulation.

We now plan to (1) validate these predictions using both ex-vivo and in-vivo investigations on peripheral nerves, and (2) couple our modular framework with acoustic propagation models to formulate more detailed predictions of neural responses upon sonication by realistic acoustic sources and to inform the development of application-specific ultrasonic devices.

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