Alterations in large-scale resting-state network nodes following transcranial focused ultrasound of deep brain structures

Background Low-intensity transcranial focused ultrasound (tFUS) is a brain stimulation approach that holds immense promise for the treatment of brain-based disorders. Several studies in humans have shown that tFUS can successfully modulate perfusion in focal sonication targets including the amygdala; however, limited research has explored how tFUS impacts the function of large-scale neural networks. Objective The aim of the current study was to address this gap and examine changes in resting-state connectivity between large-scale network nodes using a randomized, double-blind, within-subject crossover study design. Methods Healthy adults (n=18) completed two tFUS sessions, 14 days apart. Each session included tFUS of either the right amygdala or the left entorhinal cortex (ErC). The inclusion of two active targets allowed for within-subjects comparisons as a function of the locus of sonication. Resting-state functional magnetic resonance imaging was collected before and after each tFUS session. Results tFUS altered resting-state functional connectivity (rsFC) within and between rs-network nodes. Specifically, pre-to-post sonication of the right amygdala modulated connectivity within nodes of the salience network (SAN) and between nodes of the SAN and the default-mode network (DMN) and fronto-parietal network (FRP). A decrease in SAN to FPN connectivity was specific to the amygdala target. Pre-to-post sonication of the left ErC was found to modulate connectivity between the dorsal attention network (DAN) and FPN and DMN. An increase in DAN to DMN connectivity was specific to the ErC target. Conclusion These preliminary findings may suggest that tFUS induces neuroplastic changes beyond the immediate sonication target.