Transcranial Focused Ultrasound to the Right Prefrontal Cortex Improves Mood and Alters Functional Connectivity in Humans.

Transcranial focused ultrasound (tFUS) is an emerging method for non-invasive neuromodulation akin to transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). tFUS offers several advantages over electromagnetic methods including high spatial resolution and the ability to reach deep brain targets. Here we describe two experiments assessing whether tFUS could modulate mood in healthy human volunteers by targeting the right inferior frontal gyrus (rIFG), an area implicated in mood and emotional regulation. In a randomized, placebo-controlled, double-blind study, participants received 30 s of 500 kHz tFUS or a placebo control. Visual Analog Mood Scales (VAMS) assessed mood four times within an hour (baseline and three times after tFUS). Participants who received tFUS reported an overall increase in Global Affect (GA), an aggregate score from the VAMS scale, indicating a positive shift in mood. Experiment 2 examined resting-state functional (FC) connectivity using functional magnetic resonance imaging (fMRI) following 2 min of 500 kHz tFUS at the rIFG. As in Experiment 1, tFUS enhanced self-reported mood states and also decreased FC in resting state networks related to emotion and mood regulation. These results suggest that tFUS can be used to modulate mood and emotional regulation networks in the prefrontal cortex.

Introduction

Purpose Transcranial ultrasound stimulation

Study Objective To test whether transcranial focused ultrasound (tFUS) targeting the right inferior frontal gyrus can modulate mood and alter resting-state functional connectivity in healthy human volunteers.

Animal model / Human subject Human (Homo sapiens); strain: N/A; Experiment 1: final n=48 analyzed (initial n=51, 27 female), mean age 19.7 years, mixed sex (male and female); Experiment 2: n=9 (4 female), mean age 19.2 years, mixed sex (male and female).

Disease model Healthy

MRI or image guidance method International 10/20 EEG electrode placement (F8 scalp location)

Targeted brain region(s) Inferior Frontal Gyrus (Rifg), Ventrolateral Prefrontal Cortex

Target coordinates rIFG (BA45): 58, 13, 6; mPFC (BA10): 0, 48, -4; PCC (BA31): -5, -51, 39

Outcomes and Safety

Summary of Outcomes tFUS to the right inferior frontal gyrus improved self-reported mood in healthy participants. For the imaging experiment, it also changed resting-state functional connectivity, with reduced connectivity in mood related networks and default mode network 20 min after sonication.

Duration of biological effect 30 min

Safety-related matter Fifteen of 24 tFUS-Active participants reported hearing buzzing/clicking and 10/24 reported sensations (pulsing, buzzing, pressure), with a few placebo participants reporting minor sensations as well. No adverse events or safety concerns were reported, and hearing the sound did not influence mood outcomes.

Brain Region

Ultrasound Parameters

Ultrasound instrument Custom focused ultrasound system (Neurotrek, Inc., Boston, MA, United States) using a single-element 500 kHz transducer with a two-part lens focused at 30 mm (Blatek, Inc., Pittsburg, PA, United States). Aperture/diameter: None

FUS Frequency 500 kHz (0.5 MHz)

FUS Intensity 54 W/cm2 (I_sppa, measured in water); 0.130 W/cm2 (I_spta, measured in water) — Experiment 1 (30 s); 54 W/cm2 (I_sppa, measured in water); 0.272 W/cm2 (I_spta, measured in water) — Experiment 2 (2 min, duty cycle 0.5%); estimated skull-attenuated I_sppa ≤ 16.2 W/cm2 (delivered to brain)

FUS Pressure 1.27 MPa, 1.26 MPa

FUS Mode pulsed

Pulse duration 0.065 ms

Duration of a single FUS session 30 s (Experiment 1); 2 min (Experiment 2)

Focal Characteristics Focal depth: None; Focal length: 30 mm; Aperture size: None

Treatment frequency Single session

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