A Review of Mechanistic Effects of Low-Intensity Focused Ultrasound.

Low-intensity focused ultrasound (LIFU) has become increasingly used in neuromodulation. However, its mechanisms of action are less well understood. Here, we provide a scoping review of the effects of LIFU on nervous system tissue. We evaluated the PubMed, SCOPUS, and Web of Science data bases for articles using the keywords related to LIFU and neuromodulation; 3970 articles were retrieved and titles screened by two authors (AT and MH) with conflicts resolved by one author (PP). The abstract review included 837 articles, and full-text review included 371 articles; 157 articles were included in the final manuscript. The mechanisms of action of LIFU for neuromodulation have been studied in vitro, in preclinical models, and in humans. LIFU exerts both excitatory and inhibitory modulatory effects through ion channel activation, changes in neurotransmission, and certain gene expression pathways. These changes cause localized and distributed effects in brain tissue and in behavioral modification in human trials and nonhuman models, depending on stimulation parameters and region targeted. Most LIFU research focuses on cerebral neuromodulation whereas some data exist for spinal cord and peripheral nerve neuromodulation. Considerable growth in research evaluating LIFU's ability to modulate the nervous system has occurred. Although safety and efficacy have been indicated, heterogeneity in LIFU operating parameters may cause nuanced differential effects on target tissue. By further elucidating the mechanisms of LIFU neuromodulation, future research will advance treatments for chronic neurologic diseases.