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Low-intensity focused ultrasound modulates monkey visuomotor behavior.

Authors: Deffieux T, Younan Y, Wattiez N, Tanter M, Pouget P, Aubry JF

In vivo feasibility of using low-intensity focused ultrasound (FUS) to transiently modulate the function of regional brain tissue has been recently tested in anesthetized lagomorphs [1] and rodents [2-4]. Hypothetically, ultrasonic stimulation of the brain possesses several advantages [5]: it does not necessitate surgery or genetic alteration but could ultimately confer spatial resolutions superior to other noninvasive methods. Here, we gauged the ability of noninvasive FUS to causally modulate high-level cognitive behavior. Therefore, we examined how FUS might interfere with prefrontal activity in two awake macaque rhesus monkeys that had been trained to perform an antisaccade (AS) task. We show that ultrasound significantly modulated AS latencies. Such effects proved to be dependent on FUS hemifield of stimulation (relative latency increases most for ipsilateral AS). These results are interpreted in terms of a modulation of saccade inhibition to the contralateral visual field due to the disruption of processing across the frontal eye fields. Our study demonstrates for the first time the feasibility of using FUS stimulation to causally modulate behavior in the awake nonhuman primate brain. This result supports the use of this approach to study brain function. Neurostimulation with ultrasound could be used for exploratory and therapeutic purposes noninvasively, with potentially unprecedented spatial resolution.

Introduction

Purpose Drug delivery with BBB opening
Study Objective To evaluate a low-frequency hemispherical phased-array ultrasound system for transcranial BBB disruption.
Animal model / Human subject Rat, Sprague Dawley, adult, male
Disease model Healthy
MRI or image guidance method Hydrophone-based positioning
Targeted brain region(s) Parenchyma

Outcomes and Safety

Summary of Outcomes The hemispherical phased-array achieved focused sonication at center and off-center targets and sucessfully produced localized BBB disruption in rats. BBB opening increased with applied power, while high power caused hemorrhage.
Duration of biological effect 4-6 hours
Safety-related matter Severe large-scale brain tissue hemorrhage was observed at 90 W.

Brain Region

Ultrasound Parameters

Ultrasound instrument Low-frequency hemispherical ultrasound phased-array system; 31-element hemispherical phased array
FUS Frequency 270 kHz
FUS Pressure 0.49-0.74 Mpa
FUS Mode pulsed
Pulse duration 10 ms
Duration of a single FUS session 30 s
Focal Characteristics Focal depth: 75 mm Focal length: 75 mm; Aperture size: 150 mm
Treatment frequency Single session

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