Effect of Low-Intensity Transcranial Focused Ultrasound Stimulation in Patients With Major Depressive Disorder: A Randomized, Double-Blind, Sham-Controlled Clinical Trial

Abstract

Objective Low-intensity transcranial focused ultrasound (tFUS) has emerged as a promising non-invasive brain stimulation modality with high spatial selectivity and the ability to reach deep brain areas. The present study aimed to investigate the safety and effectiveness of low-intensity tFUS in treating major depressive disorder. Methods Participants were recruited in an outpatient clinic and randomly assigned to either the verum tFUS or sham stimulation group. The intervention group received six sessions of tFUS stimulation to the left dorsolateral prefrontal cortex over two weeks. Neuropsychological assessments were conducted before and after the sessions. Resting-state functional magnetic resonance imaging (rsfMRI) was also performed to evaluate changes in functional connectivity (FC). The primary outcome measure was the change in depressive symptoms, assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS). Results The tFUS stimulation sessions were well tolerated without any undesirable side effects. The analysis revealed a significant main effect of session sequence on the MADRS scores and significant interactions between the session sequences and groups. The rsfMRI analysis showed a higher FC correlation between the right superior part of the subgenual anterior cingulate cortex (sgACC) and several other brain regions in the verum group compared with the sham group. Conclusion Our results reveal that tFUS stimulation clinically improved MADRS scores with network-level modulation of a sgACC subregion. This randomized, sham-controlled clinical trial, the first study of its kind, demonstrated the safety and probable efficacy of tFUS stimulation for the treatment of depression.

Abstract via europepmc.

Flags from extraction

• exposures[0].in_situ.ispta_w_cm2 — The source sentence internally contradicts itself, stating the in-situ intensity is both '600 mW/cm2 spatial-peak temporal average intensity' and, in the same parenthetical, '300 mW/cm2 spatial-peak temporal average intensity'; the first-stated value (600 mW/cm2 = 0.6 W/cm2) was recorded, but this discrepancy should be checked against the source.
• n_subjects — Paper gives multiple counts across the enrollment pipeline: 13 verum assigned at randomization, but only 11 verum patients completed the study (N=11 verum, N=12 sham of 23 total completers); it is unclear how many of the 13 randomized to verum actually received at least one sonication, since 2 of 26 randomized participants discontinued before completing tFUS sessions from an unspecified group.
• exposures[0].timing.pulse_repetition_frequency_hz — Paper states pulse (tone burst) duration and duty cycle but never states an explicit PRF or inter-pulse period, so PRF cannot be recorded without computing it from duty cycle/pulse duration.
• direction_of_effect — This is a clinical trial reporting symptom and functional-connectivity outcomes rather than a direct measurement of neural excitation/inhibition at the stimulation site; classified as not_assessed for the neuromodulation direction field.
• auditory_control — Paper does not describe an explicit auditory-masking procedure; classified as 'none' based on the authors' statement that no patients reported auditory phenomena and their suggestion that masking be used in future studies, implying none was used here.