A systematic review of focused ultrasound for psychiatric disorders: current applications, opportunities, and challenges
Authors: Henn Matthew C. , Smith Haley D. , Lopez Ramos Christian G. , Shafie Beck , Abaricia Jefferson , Stevens Ian , Rockhill Alexander P. , Cleary Daniel R. , Raslan Ahmed M. 
Published: September 2024

OBJECTIVE
Advancements in MRI-guided focused ultrasound (MRgFUS) technology have led to the successful treatment of select movement disorders. Based on the comparative success between ablation and deep brain stimulation, interest arises in focused ultrasound (FUS) as a promising treatment modality for psychiatric illnesses. In this systematic review, the authors examined current applications of FUS for psychiatric conditions and explored its potential opportunities and challenges.

METHODS
The authors performed a comprehensive review using the PRISMA guidelines of studies investigating psychiatric applications for FUS. Articles indexed on PubMed between 2014 to 2024 were included. The authors synthesized the psychiatric conditions treated, neural targets, outcomes, study design, and sonication parameters, and they reviewed important considerations for the treatment of psychiatric disorders with FUS. They also discussed active clinical trials in this research domain.

RESULTS
Of 250 articles, 10 met the inclusion criteria. Eight articles investigated the clinical, safety, and imaging correlates of MRgFUS in obsessive-compulsive disorder (OCD), whereas 3 examined treatment-resistant depression. Bilateral anterior capsulotomy resulted in a full responder rate of 67% (≥ 35% reduction in the Yale-Brown Obsessive-Compulsive Scale score) and 33% (≥ 50% reduction in the score on the Hamilton Rating Scale for Depression) in OCD and treatment-resistant depression, respectively. Sonications ranged from 8 to 36 with targeted lesional temperatures of 51°C–56°C. Lesions in the anterodorsal aspect of the anterior limb of the internal capsule (ALIC) and increased functional connectivity to the left dorsolateral prefrontal cortex and dorsal anterior cingulate cortex significantly predicted reduction in symptoms among patients with OCD, with decreases in beta-band activity in the frontocentral and temporal regions associated with reductions in depression and anxiety. Treatment of the nucleus accumbens with low-intensity FUS (LIFU) in patients with opioid-use disorders resulted in significant reductions in cue-reactive cravings, lasting up to 90 days. No serious adverse events were reported, including cognitive decline. Side effects were generally mild and transient, consisting of headaches, pin-site swelling, and nausea. Fourteen active clinical trials were identified, primarily targeting depression with LIFU.

CONCLUSIONS
Currently, FUS for psychiatric conditions is centered on OCD, with early pilot studies demonstrating promising safety and efficacy. Further research expanding on defining optimal patient selection, study design, intensity, and sonication parameters is warranted, particularly as FUS expands to other psychiatric illnesses and incorporates LIFU paradigms. Ethical considerations such as patient consent and equitable access also remain paramount.