Non-invasive transcranial ultrasound stimulation for neuromodulation

Transcranial ultrasound stimulation (TUS) holds great potential as a tool to alter neural circuits non-invasively in both animals and humans. In contrast to established non-invasive brain stimulation methods, ultrasonic waves can be focused on both cortical and deep brain targets with the unprecedented spatial resolution as small as a few cubic millimeters. This focusing allows exclusive targeting of small subcortical structures, previously accessible only by invasive deep brain stimulation devices. The neuromodulatory effects of TUS are likely derived from the kinetic interaction of the ultrasound waves with neuronal membranes and their constitutive mechanosensitive ion channels, to produce short term and long-lasting changes in neuronal excitability and spontaneous firing rate. After decades of mechanistic and safety investigation, the technique has finally come of age, and an increasing number of human TUS studies are expected. Given its excellent compatibility with non-invasive brain mapping techniques, such as electroencephalography (EEG) and functional magnetic resonance imaging (fMRI), as well as neuromodulatory techniques, such as transcranial magnetic stimulation (TMS), systemic TUS effects can readily be assessed in both basic and clinical research. In this review, we present the fundamentals of TUS for a broader audience. We provide up-to-date information on the physical and neurophysiological mechanisms of TUS, available readouts for its neural and behavioral effects, insights gained from animal models and human studies, potential clinical applications, and safety considerations. Moreover, we discuss the indirect effects of TUS on the nervous system through peripheral co-stimulation and how these confounding factors can be mitigated by proper control conditions. (C) 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Automated summary

Transcranial ultrasound stimulation (TUS) has the potential to alter neural circuits non-invasively in both animals and humans. Unlike other non-invasive brain stimulation methods, TUS can focus on both cortical and deep brain targets with unprecedented spatial resolution. The neuromodulatory effects of TUS are derived from the interaction of ultrasound waves with neuronal membranes, resulting in changes in excitability and firing rate. After years of research, TUS is now being applied in human studies and can be assessed using non-invasive brain mapping techniques. This review provides a comprehensive overview of the principles, mechanisms, effects, and potential applications of TUS.