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

Authors: Gorka SM, Jimmy J, Koning K, Phan KL, Rotstein N, Hoang-Dang B, Halavi S, Spivak N, Monti MM, Reggente N, Bookheimer SY, Kuhn TP

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. 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. Healthy adults (<i>n =</i> 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. 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. 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.

Introduction

Purpose Transcranial ultrasound stimulation
Study Objective To determine whether low-intensity transcranial focused ultrasound targeting the right amygdala versus the left entorhinal cortex alters resting-state functional connectivity between large-scale brain networks in healthy adults.
Animal model / Human subject Homo sapiens (human); strain: N/A; age: healthy adults, mean 61.38 years (SD 7.75), range 48–79 years; sex: mixed (56% female)
Disease model Healthy
MRI or image guidance method Real-time structural MRI navigation inside the scanner (MRI-guided); a 30-s SCOUT imaging sequence was used to visualize the transducer and its orthogonal targeting line, with the transducer placed at the temporal window and manually adjusted to target (focal depth 65 mm or 55 mm).
Targeted brain region(s) Amygdala And Entorhinal Cortex (Erc)

Outcomes and Safety

Summary of Outcomes tFUS altered resting state connectivity, right amygdala sonication modulated the salience network, while left entorhinal cortex sonication increased dorsal attention network connectivity with the DMN and the frontoparietal network.
Safety-related matter The authors cite prior studies indicating low-intensity tFUS does not operate via thermal or tissue-damaging mechanisms and describe tFUS as feasible and able to target deep brain areas without engaging nearby structures; the paper does not report any observed adverse effects or safety events in the current study.

Brain Region

Ultrasound Parameters

Ultrasound instrument Single-element transducer (BrainSonix Corp., Sherman Oaks, CA, USA); focal sonication depth 65 mm or 55 mm; transducer aperture/diameter: None
FUS Frequency 0.65 MHz
FUS Intensity 0.72 W/cm2
FUS Mode pulsed
Pulse duration 5 ms (amygdala); 0.5 ms (ErC)
Duration of a single FUS session 5 minutes
Focal Characteristics Focal depth: 65 mm or 55 mm; Focal length: None; Aperture size: None
Treatment frequency Multiple sessions

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