Focused ultrasound neuromodulation for psychiatric disorders: a scoping review of clinical applications and current progress

Low-intensity focused ultrasound (LIFU/FUS) is a precise, reversible, incisionless technology that has demonstrated potential efficacy as a neuromodulatory therapy for psychiatric disorders. While high-intensity focused ultrasound (HIFU) is routinely used in ablative neurosurgical procedures, low-intensity focused ultrasound remains investigational and is not yet ready for widespread clinical use. FUS leverages mechanisms including mechanotransduction, sonoporation, or flexoelectric effects to excite or inhibit neural tissue. In this scoping review, we synthesize the current evidence on therapeutic efficacy, safety, and sonication parameters, examining outcomes across diverse psychiatric indications. Our search identified 320 studies, of which 14 met our inclusion criteria. All studies investigated neuromodulatory FUS in subjects with psychiatric diagnoses including major depressive disorder (MDD), generalized anxiety disorder (GAD), schizophrenia, obsessive-compulsive disorder (OCD), and substance use disorder (SUD). Symptomatic improvement was reported across psychiatric indications; however, positive randomized trial results have only been demonstrated in a subset of trials, while evidence for other indications remains preliminary and is largely derived from small open-label cohorts. Effect durability was mixed. Across protocols, substantial heterogeneity exists in sonication devices, parameters, and cranial targets, suggesting a lack of consensus for technical aspects of this emerging technology. Two serious adverse events were reported. Early evidence from this emerging field suggests that FUS may improve outcomes across a variety of psychiatric indications; however, significant challenges remain, including protocol and parameter optimization, regulatory approval, and ethical considerations, emphasizing the need for continued research and interdisciplinary collaboration to optimize FUS as a therapeutic modality for patients with treatment-resistant psychiatric disorders.