Advancing Non-invasive Brain Stimulation with Low-intensity Transcranial FUS (tFUS)

Abstract

Transcranial focused ultrasound (tFUS), particularly at non-thermal low intensities delivered in pulsed schemes, has gained increasing attention as a novel approach for non-invasive brain stimulation. Unlike conventional electrical or magnetic stimulation techniques, tFUS offers the unique advantages of millimeter-scale spatial resolution and the ability to reach deep brain structures without surgical intervention. Over the past decade, a series of studies have investigated the feasibility and potential of tFUS across diverse models, including small animals, large animals, and human participants. These investigations show that tFUS can modulate neuronal activity in both excitatory and inhibitory directions, alter functional connectivity, and elicit behavioral and physiological responses in a reproducible and safe manner. As a form of therapeutic ultrasound applied to the nervous system, tFUS provides a unique opportunity to explore non-invasive neuromodulation with translational relevance. While the breadth of research spans multiple species, this presentation will highlight representative findings with an emphasis on selected examples most relevant to the advancement of non-invasive brain stimulation. Key experimental results, methodological considerations, and lessons learned from cross-species investigations will be summarized. Although the precise mechanisms underlying ultrasound-induced neuromodulation remain to be fully elucidated, the accumulated evidence indicates that tFUS holds significant promise as a modality for non-invasive brain stimulation. By outlining both opportunities and challenges identified through this body of work, the talk will share insights into the current potential of tFUS and its place within the broader context of therapeutic ultrasound.