Spatiotemporal Reconfiguration of Functional Brain Networks Following Transcranial Focused Ultrasound Stimulation

OBJECTIVES: Transcranial focused ultrasound stimulation (TUS) is an emerging neuromodulatory technique capable of modulating cortical and subcortical brain regions with high spatial precision. However, its effects on large-scale functional brain networks and their temporal evolution remain incompletely understood. This study investigated whether brief theta burst TUS induces target-specific alterations in functional brain network topology over the first hour after stimulation. MATERIALS AND METHODS: A total of 22 healthy participants were randomly assigned to receive TUS targeting either the right inferior frontal cortex (IFC) or the right thalamus. Resting-state functional magnetic resonance imaging was acquired at baseline and at three minutes post stimulation intervals spaced 15 minutes apart. Graph-theoretical analyses quantified four centrality metrics (strength, expected influence, betweenness, and closeness) across 86 brain regions. Global network organization was assessed using small-worldness. RESULTS: IFC stimulation produced progressive reductions in regional network integration, initially affecting visual cortices and subsequently extending to right prefrontal and temporal regions, the insula, and the putamen, with peak effects occurring approximately 45 minutes post stimulation. IFC stimulation also increased global small-worldness, indicating a shift toward a more randomized network configuration. In contrast, thalamic stimulation resulted in a spatially circumscribed and temporally stable reduction in betweenness centrality within the left precuneus without widespread network alterations. CONCLUSIONS: Brief theta burst TUS induces target-dependent and temporally evolving changes in large-scale functional brain organization. Cortical stimulation of the IFC produced distributed and progressive network reconfiguration, whereas thalamic stimulation yielded a focal and stable effect. These findings suggest that the magnitude and spatial extent of TUS-induced network modulation depend on the connectivity profile and topologic embedding of the stimulated structure.