Low-Intensity Focused Ultrasound Neuromodulation for Stroke Recovery: A Novel Deep Brain Stimulation Approach for Neurorehabilitation?

Authors: Yuksel MM, Sun S, Latchoumane C, Bloch J, Courtine G, Raffin EE, Hummel FC

Stroke as the leading cause of adult long-term disability and has a significant impact on patients, society and socio-economics. Non-invasive brain stimulation (NIBS) approaches such as transcranial magnetic stimulation (TMS) or transcranial electrical stimulation (tES) are considered as potential therapeutic options to enhance functional reorganization and augment the effects of neurorehabilitation. However, non-invasive electrical and magnetic stimulation paradigms are limited by their depth focality trade-off function that does not allow to target deep key brain structures critically important for recovery processes. Transcranial ultrasound stimulation (TUS) is an emerging approach for non-invasive deep brain neuromodulation. Using non-ionizing, ultrasonic waves with millimeter-accuracy spatial resolution, excellent steering capacity and long penetration depth, TUS has the potential to serve as a novel non-invasive deep brain stimulation method to establish unprecedented neuromodulation and novel neurorehabilitation protocols. The purpose of the present review is to provide an overview on the current knowledge about the neuromodulatory effects of TUS while discussing the potential of TUS in the field of stroke recovery, with respect to existing NIBS methods. We will address and discuss critically crucial open questions and remaining challenges that need to be addressed before establishing TUS as a new clinical neurorehabilitation approach for motor stroke recovery.

Introduction

Purpose Transcranial ultrasound stimulation (TUS)

Study Objective To review current knowledge on transcranial ultrasound stimulation's neuromodulatory effects and critically discuss its potential and challenges for use in motor stroke recovery compared with existing non-invasive brain stimulation methods.

Disease model Stroke

Outcomes and Safety

Summary of Outcomes Transcranial ultrasound stimulation (TUS) can modulate cortical excitability, enhance neuroplasticity, and promote functional recovery after stroke in animal and preliminary human studies. However, no consistent set of effective focused‑ultrasound parameters was identified — studies generally used parameter ranges within FDA‑approved diagnostic ultrasound limits (varying frequency, intensity, duration, and pulsed vs continuous modes) but specific successful parameter values were not established.

Safety-related matter The review states that most TUS parameters used in studies fall within FDA-approved diagnostic ultrasound settings but emphasizes the absence of formal consensus on safety standards and the need for further evaluation of safe protocols; it also recommends reporting mechanical/thermal safety and any unwanted effects. Some studies have reported adverse effects such as headache, nausea, and dizziness, so safety and tolerability must be carefully assessed in future human studies.

Brain Region

Visualization unavailable

Ultrasound Parameters

Focal Characteristics focal depth: None; focal length: None; aperture size: None

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