Ultrasound Neuromodulation of Circuits and Negative Valence Systems in Treatment-Resistant Depression

Approximately one third of individuals with Major Depressive Disorder (MDD) are considered treatment-resistant, subject to severe disability and risk of suicide, and exhibit symptoms anchored in abnormalities of Research Domain Criteria (RDoC) Negative Valence Systems behavioral processes. In the present study we plan to use low-intensity focused ultrasound in 120 persons with treatment-resistant MDD to modulate deep white matter tracts connecting the thalamus and different regions of the prefrontal cortex reversibly and non-invasively, with the aim of assigning a causal, mechanistic role to large scale brain circuits in the production of those critical behavioral abnormalities. A successful study will help to attain the precise definition of neuromodulation targets for this clinical population in utter need of help.

NCT Number	NCT07166289
Lead Sponsor	Laureate Institute for Brain Research, Inc.
Conditions	Treatment-Resistant Depression
Enrollment	140 participants
Start Date	2025-09-30
Primary Completion	2030-04 (estimated)
Study Completion	2030-07 (estimated)
Updated on ClinicalTrials.gov	2026-03-02