Focused Ultrasound Neuromodulation for Psychiatric Disorders: A Review of Clinical Applications

Introduction: Focused ultrasound (FUS) has emerged as a promising noninvasive neuromodulation technique which may offer therapeutic benefits for patients with medically refractory psychiatric disorders or those who are not surgical candidates. Multiple mechanisms are proposed to underlie the neuromodulatory effects of FUS, including activation of mechanosensitive Piezo channels, sonoporation-induced changes in membrane permeability, cavitation, flexoelectric effects, or combined effects. In this review, we assessed current indications and outcomes of neuromodulatory FUS across a range of psychiatric conditions.

Methods: We completed a SCOPING review of primary literature including completed randomized controlled trials on PubMed through October 2024 to identify all studies which directly examined FUS neuromodulation for psychiatric disorders in humans. We included studies with both healthy and unhealthy populations. We excluded papers which did not explicitly explore a clinical indication (i.e., increased theta band power). Clinical indications, outcome metrics, anatomical targets, sonication devices and parameters, and adverse events were noted.

Results: A total of 22 relevant articles were identified. 9 studies primarily targeted major depressive disorder (MDD), 5 on generalized anxiety disorder (GAD), 3 on disorders of consciousness (DOC), 2 on substance use disorder (SUD), 1 on schizophrenia, 1 on attention deficit-hyperactivity disorder (ADHD), and 1 other (visual hallucination). Common targets of sonication were the dorsolateral prefrontal cortex and cingulate cortex (MDD), amygdala (GAD), and thalamus (DOC). Across all studies, FUS was well-tolerated with no severe adverse effects reported. Sonication devices and parameters varied substantially between protocols with no clear patterns of standardization.

Conclusion : FUS effectively modulates brain areas implicated in psychiatric disorders and may offer substantial benefits to patients with treatment-conditions as either a standalone or adjuvant treatment. Though MDD is the most investigated indication thus far, more studies are beginning to examine other disorders. Ultrasound device choice and sonication parameters vary widely between studies, highlighting the need for standardization if FUS is to scale clinically. Research is needed to determine effect sizes over time, expand clinical indications, and optimize sonication parameters.