LOW-INTENSITY TRANSCRANIAL FOCUSED ULTRASOUND NEUROMODULATION: MECHANISMS, CLINICAL APPLICATIONS, SAFETY, AND FUTURE DIRECTIONS

Abstract

Background. Low-intensity transcranial focused ultrasound is an emerging noninvasive neuromodulation technology capable of targeting cortical and deep cerebral structures with greater spatial selectivity than conventional electrical or magnetic stimulation. Unlike high-intensity focused ultrasound, it is intended to modify neural activity without producing permanent tissue ablation.

Materials and methods. A concise narrative review was conducted using experimental studies, early clinical trials, technical investigations, and international reporting and safety recommendations. Evidence was evaluated according to biological mechanism, acoustic parameters, target engagement, clinical applicability, safety, and reproducibility.

Results. Ultrasound may influence neuronal activity through acoustic radiation force, membrane deformation, mechanosensitive ion channels, synaptic modulation, and neurovascular mechanisms. Human studies demonstrate modulation of the motor cortex, thalamus, basal ganglia, hippocampus, amygdala, and distributed functional networks. Preliminary therapeutic applications include Parkinson’s disease, drug-resistant epilepsy, depression, disorders of consciousness, chronic pain, and post-stroke rehabilitation. However, clinical studies remain limited by small samples, heterogeneous sonication protocols, variable sham conditions, skull-related acoustic distortion, and insufficient long-term follow-up.

Conclusion. Low-intensity focused ultrasound provides a promising platform for reversible and anatomically precise neuromodulation. Nevertheless, it remains predominantly investigational. Individualized acoustic modeling, standardized dose reporting, credible sham control, objective target-engagement biomarkers, and multicenter validation are required before routine clinical implementation.