The relationship between parameters and effects in transcranial ultrasonic stimulation

TL;DR

This review synthesizes empirical evidence on how various parameters of transcranial ultrasonic stimulation influence neuromodulatory effects, highlighting optimal settings and challenges in translating findings to human applications.

Contribution

It provides a comprehensive analysis of the relationship between TUS parameters and outcomes, guiding future protocol development for effective neuromodulation.

Findings

Lower frequencies within sub-MHz range produce larger effects

Higher intensities and pressures than currently used enhance efficacy

Longer pulse durations may improve neuromodulatory outcomes

Abstract

Transcranial ultrasonic stimulation (TUS) is rapidly gaining traction for non-invasive human neuromodulation, with a pressing need to establish protocols that maximise neuromodulatory efficacy. In this review, we aggregate and examine empirical evidence for the relationship between tunable TUS parameters and in vitro and in vivo outcomes. Based on this multiscale approach, TUS researchers can make better informed decisions about optimal parameter settings. Importantly, we also discuss the challenges involved in extrapolating results from prior empirical work to future interventions, including the translation of protocols between models and the complex interaction between TUS protocols and the brain. A synthesis of the empirical evidence suggests that larger effects will be observed at lower frequencies within the sub-MHz range, higher intensities and pressures than commonly administered thus far, and longer pulses and pulse train durations. Nevertheless, we emphasise the need for cautious interpretation of empirical data from different experimental paradigms when basing protocols on prior work as we advance towards refined TUS parameters for human neuromodulation.