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

Abstract

Background: Low-intensity transcranial focused ultrasound (tFUS) is a brain stimulation approach that holds promise for the treatment of brain-based disorders. 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 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-subjects 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. 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 frontoparietal network (FRP). A decrease in SAN to FPN connectivity was specific to the amygdala target. Pre-to-post sonication of the left ErC modulated 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. Additional studies are needed to determine the long-term stability of these effects.

Keywords: amygdala; default mode network; entorhinal cortex; resting-state functional connectivity; salience network (SN); transcranial focused ultrasound.

Figure 1

Illustration of the MRI-guided set-up.

Figure 2

(A,B) Circular plots summarizing significant region of interest (ROI)-to-ROI connections in a paired test for the amygdala (Figure 1A) and entorhinal cortex (Figure 1B) targets, highlighting differences at p < 0.01. The plot was generated using the CONN toolbox. Significant connections are indicated by colored lines, with red lines representing connections that had greater connectivity post-tFUS compared to pre-tFUS and blue representing connections that had greater connectivity pre-tFUS compared to post-tFUS. The intensity of the colors correlates with the strength of the connections, as shown in the color bar. The inset shows the brain regions involved in the analysis. (A) Includes connections between the default mode network (PCC), frontoparietal network (LPFC), and salience network (RPFC and anterior insula). (B) Includes connections between the default mode network (mPFC), frontoparietal network (RPFC), and dorsal attention network (IPS). The bar graphs display extracted connectivity parameter estimates from node connections that were found to significantly differ pre-to-post sonication.