Major depressive disorder (MDD) is a leading cause of disability worldwide with one-third of cases being treatment resistant. Symptom heterogeneity suggests variability across affected brain networks, prompting efforts to personalize circuit-based neuromodulatory interventions. For example, personalized deep brain stimulation (DBS) has been achieved by selecting different treatment targets based on phenotypes or mapping stimulation responses. However, DBS is invasive, and the stability of optimal long-term treatment within a dynamic and adaptive brain remains unknown. Noninvasive approaches, such as transcranial magnetic stimulation (TMS), have shown promise in modulating putative mood networks but are unable to target deeper subcortical regions.
Transcranial ultrasound stimulation (TUS) or low intensity focused ultrasound is an emerging, non-invasive method with millimeter spatial specificity and a unique ability to achieve deep subcortical neuromodulation. TUS can reversibly modulate brain networks and confer durable behavioral effects. Preliminary studies suggest that TUS applied to classical TMS and DBS targets can improve anxiety, worry, avoidance and mood. To examine whether dynamically steered TUS may identify personalized therapeutic subregions in MDD, Chen Scholar, Joline M. Fan at UCSF worked with fellow researchers to employ a dual-phased array crossbeam focusing to stimulate subcortical mood-related circuitry.