Low-intensity ultrasound neuromodulation: An overview of mechanisms and emerging human applications

Background There is an emerging need for noninvasive neuromodulation techniques to improve patient outcomes while minimizing adverse events and morbidity. Low-intensity focused ultrasound (LIFUS) is gaining traction as a non-surgical experimental approach of modulating brain activity. Several LIFUS sonication parameters have been found to potentiate neural firing, suppress cortical and epileptic discharges, and alter behavior when delivered to cortical and subcortical mammalian brain regions. Objective This review introduces the elements of an effective sonication protocol and summarizes key preclinical studies on LIFUS as a neuromodulation modality. The state of the art in human ultrasound neuromodulation is then comprehensively summarized, and current hypotheses regarding the underlying mechanism of action on neural activity are presented. Methods Peer-reviewed literature on human ultrasound neuromodulation was obtained by searching several electronic databases. The abstracts of all reports were read and publications which examined low-intensity transcranial ultrasound applied to human subjects were selected for review. Results LIFUS can noninvasively influence human brain activity by suppressing cortical evoked potentials, influencing cortical oscillatory dynamics, and altering outcomes of sensory/motor tasks compared to sham sonication. Proposed mechanisms include cavitation, direct effects on neural ion channels, and plasma membrane deformation. Conclusions Though optimal sonication paradigms and transcranial delivery methods are still being established, future applications may include non-invasive human brain mapping experiments, and nonsurgical treatments for functional neurological disorders.