Transcranial focused ultrasound for emotion regulation: A systematic review and quantitative summary of human studies.

Clinical Snapshot

Key Findings

• P Value: Not reported in abstract

• Effect Size: Hedges' g = 0.88 (moderate-to-large); depression subgroup g = 1.31; anxiety subgroup g = 0.67

• Primary Outcome: Pooled behavioural symptom outcomes across 6 studies using tFUS for emotion regulation (depression and anxiety measures)

• Nnt Or Sensitivity: NNT not calculable from available data; no standardised clinical threshold applied. Prediction intervals not reported. Subgroup effect sizes suggest larger signal in depression-related outcomes than anxiety-related outcomes.

• Confidence Interval: 95% CI [0.47, 1.29] for overall pooled estimate

Clinical Application

tFUS remains an investigational technology. Clinical-grade devices are not yet widely available outside specialist research centres. Stimulation protocols are not standardised, and optimal parameters for affective indications remain undefined. The technology's key advantages — submillimetre focality and deep structure access (amygdala, subcallosal cingulate) — are theoretically compelling but require validation in adequately powered trials. tFUS is not currently TGA-approved for any psychiatric indication in Australia. TMS (via devices such as the NeuroStar and BrainsWay systems) is available for treatment-resistant depression and is supported under MBS item numbers for eligible patients. tDCS remains largely investigational in Australian clinical practice. RACGP and RANZCP guidelines do not currently reference tFUS for mood or anxiety disorders. Australian researchers at institutions with MRI-guided focused ultrasound infrastructure (e.g., major academic medical centres) may be positioned to contribute to the emerging trial evidence base. PBS listing for tFUS is not applicable at this stage. Clinicians should be aware of this technology as a potential future option but should not recommend it outside registered clinical trials. Adults with mood disorders (particularly depression), anxiety disorders, and stress-related conditions where standard neuromodulation approaches (TMS, tDCS) have been insufficient or where deep subcortical target engagement is desired. Currently applicable only in research settings.

Abstract

BACKGROUND: Emotion regulation is a core transdiagnostic process in mood, anxiety, and stress-related disorders. While existing non-invasive brain stimulation approaches, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), can modulate affective networks, their clinical use is limited by restricted spatial precision and depth penetration. Transcranial focused ultrasound stimulation (tFUS) offers submillimeter focality and access to both cortical and deep subcortical structures, making it a promising tool for affective neuromodulation. METHODS: We systematically searched PubMed, Embase, and PsycINFO for human studies using tFUS to modulate emotion regulation, affective processing, or related symptoms. Eligible studies included randomized controlled trials (RCTs), open-label, and within-subject designs. Data on stimulation parameters, target regions, outcomes, and safety were extracted. Effect sizes were calculated and pooled using a random-effects model, with subgroup analyses by clinical domain. RESULTS: Eleven studies met inclusion criteria, targeting the amygdala (n = 5), prefrontal cortex (n = 5), or subcallosal cingulate cortex (n = 1), with protocols varying in frequency (250-650 kHz), duty cycle (0.5-70%), and number of sessions (1-25). Across six studies reporting behavioral symptom outcomes, the pooled effect was moderate-to-large (Hedges' g = 0.88, 95% CI [0.47, 1.29]), with larger effects in depression-related measures (g = 1.31) than in anxiety-related measures (g = 0.67). Imaging outcomes were reported in a smaller subset of studies and were not included in the pooled estimates. No serious adverse events were reported. CONCLUSIONS: tFUS is a safe and well-tolerated intervention capable of engaging deep affective circuits; however, quantitative estimates remain preliminary given the small and heterogeneous evidence base. Future large-scale, harmonized, and mechanistically informed trials are warranted to refine protocols, establish durability, and optimize translation into clinical practice.

References

1. 1.Kang, Y., Han, K.-M., Ham, B.-J., Auer, D. P., Kaiser, M., & Jung, J. (2026). Transcranial focused ultrasound for emotion regulation: A systematic review and quantitative summary of human studies. Journal of Affective Disorders. https://doi.org/10.1016/j.jad.2026.121621