High-Intensity Focused Ultrasound (HIFU) and Low-Intensity Focused Ultrasound (LIFU) as neurosurgical approaches in psychiatry: A systematic review of current clinical evidence

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Objectives Transcranial focused ultrasound (tFUS), including high-intensity focused ultrasound (HIFU) and low-intensity focused ultrasound (LIFU), has emerged as an incisionless approach for modulating or ablating brain circuits implicated in psychiatric disorders. This systematic review summarizes the current clinical evidence on HIFU and LIFU for psychiatric indications, with emphasis on clinical outcomes, safety, targets, and methodological limitations. However, HIFU has primarily been investigated for incisionless ablative procedures, whereas LIFU has mainly been explored as a reversible neuromodulation technique. Given these distinct therapeutic objectives, direct comparison between both modalities should be interpreted cautiously. Materials and Methods A systematic literature search was conducted in PubMed/MEDLINE, Embase, Scopus, and Cochrane for studies published between 2014 and 2025 evaluating HIFU and LIFU in adults with psychiatric or neuropsychiatric disorders. Clinical trials, pilot studies, open-label studies, and sham-controlled studies reporting clinical outcomes, stimulation or ablation targets, and adverse events were included. Studies involving nonpsychiatric indications, animal models, reviews, editorials, protocols, or other neuromodulation techniques that did not use focused ultrasound as the primary intervention were excluded. Results Eight studies met the inclusion criteria, comprising three HIFU and five LIFU studies. HIFU studies primarily evaluated magnetic resonance-guided bilateral capsulotomy targeting the anterior limb of the internal capsule in treatment-refractory obsessive-compulsive disorder and major depressive disorder. LIFU studies evaluated nonablative neuromodulation of fronto-limbic targets in mood, anxiety, trauma-related, and psychotic disorders. Across studies, focused ultrasound was associated with improvements in several psychiatric rating scales. Reported adverse effects were generally mild and transient, most commonly headache, dizziness, scalp sensitivity, or procedure-related discomfort. However, evidence was limited by small sample sizes, heterogeneous diagnoses, variable follow-up, and risk of bias. Conclusions Preliminary clinical evidence suggests that HIFU and LIFU may be associated with symptom improvement in selected psychiatric populations. Larger randomized, sham-controlled, multicenter trials are required to define efficacy, safety, optimal targets, and clinical implementation.

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