Low-Intensity Focused Ultrasound Neuromodulation in Psychiatric Disorders: Mechanisms, Models, and Missing Links.

Low-intensity focused ultrasound (FUS) is emerging as a promising noninvasive neuromodulation technique with the potential to deliver reversible and focal deep brain stimulation. FUS's high spatial precision and noninvasiveness set it apart from current brain stimulation technologies such as transcranial magnetic, transcranial electrical, and deep brain stimulation. Among noninvasive neuromodulatory techniques, it has the unique ability to target deep brain structures implicated in psychiatric illness. Recent studies have demonstrated its potential to improve symptoms across a broad range of psychiatric disorders, including major depressive, generalized anxiety, and substance use disorders. In this article, we review the mechanisms of FUS across molecular, synaptic, and network levels, drawing on preclinical and early clinical evidence. While preliminary findings support the safety of FUS, further research is required to characterize mechanisms, optimize sonication parameters, and establish its possible acute and longer-term efficacy as a neurocircuit-based treatment. Technical challenges remain, including precise localization of the ultrasound beam and the need for validated imaging approaches to confirm target engagement. Importantly, growing evidence suggests that FUS can induce physiological effects such as altered perfusion and changes in excitability that appear to persist well beyond the period of sonication, underscoring its potential for durable circuit-level modulation. Addressing these opportunities and challenges will be essential for guiding precision clinical trials and unlocking the full therapeutic promise of FUS. If realized, the incorporation of FUS into psychiatric care could transform the landscape of neuromodulation and clinical therapeutics.