Transcranial Focused Ultrasound for Emotion Regulation: A Systematic Review and Quantitative Summary of Human Studies

Abstract Background: Emotion regulation is a core transdiagnostic process in mood, anxiety, and stress–related disorders. While 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 high 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). tFUS modulated emotion-related neural circuits, reduced symptoms, and altered functional connectivity. The pooled effect size across six studies was significant (Hedges′ g = 0.88, 95% CI [0.47, 1.29]), with larger effects for depression (g = 1.31) than anxiety (g = 0.67). No serious adverse events were reported. Conclusions: tFUS is a safe, well–tolerated, and effective intervention capable of engaging deep affective circuits. Future large–scale, harmonized, and mechanistically informed trials are warranted to refine protocols, establish durability, and optimize translation into clinical practice.