Modulation of Human Brain Functional Connectivity with Transcranial Focused Ultrasound Stimulation

Transcranial focused ultrasound stimulation (tFUS) is being increasingly investigated as a non-invasive approach to interrogate brain circuits and treat psychiatric disorders marked by aberrant brain activity. However, the mechanisms of tFUS, as well as its effects on large-scale brain networks, remain unclear. Here, we asked whether tFUS can reliably modulate functional connectivity (FC) with a deep brain region: the subgenual anterior cingulate cortex (sgACC), a clinically relevant area implicated in mood disorders. Using functional magnetic resonance imaging (fMRI), we recorded blood-oxygen-level dependent (BOLD) activity before, during, and after 5 minutes of tFUS targeting the sgACC. Relative to sham stimulation, we found a statistically significant increase in FC with the target both during and immediately after sonication. The increase manifested as a slow increase that was observed in approximately 80% of the sgACC's connections, suggesting enhanced integration of the sgACC into large-scale networks. These findings support the feasibility of tFUS as a tool for modulating activity in deep brain regions with potential therapeutic applications.