The effect of non-invasive transcranial focused ultrasound for depression on the default mode network: an open-label pilot trial.

Background: Major depressive disorder (MDD) affects one in five individuals, often recurs, and up to 50% of cases are deemed treatment resistant. Aberrant brain connectivity is associated with both depression symptoms and a thought pattern characteristic of depression, repetitive negative thought (RNT). Transcranial focused ultrasound (tFUS) is a novel neuromodulation technique that can directly target a hypothesized neural mechanism in depression, default mode network (DMN) hyperconnectivity. The present study assessed whether tFUS decreases DMN connectivity in individuals with MDD. Exploratory analyses assessed whether changes in DMN connectivity tracked changes in depressive symptoms and RNT. Methods: Twenty participants with MDD completed up to 11 sessions of tFUS treatment targeting the left anterior medial prefrontal cortex, a major hub of the DMN. Before commencing and after completing treatment, participants completed resting state functional magnetic resonance imaging, self -report assessments, and clinical interviews. Participants also completed daily self-report and adverse event assessments. Results: We previously reported a significant decrease in depression symptoms and RNT after tFUS treatment. Here we report that DMN connectivity between the left medial prefrontal cortex and left posterior cingulate cortex, major hubs of the DMN, significantly decreased after treatment. Exploratory analysis revealed no significant relationship between change in DMN connectivity and change in depressive symptoms or RNT. Conclusions: tFUS shows promise in the treatment for MDD, as hyperconnectivity within the DMN decreased, alongside decreases in depression symptoms and RNT. These findings provide evidence supporting future clinical trials. Clinical trial registration: https://clinicaltrials.gov/study/NCT06320028, identifier NCT06320028.