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Real time and delayed effects of subcortical low intensity focused ultrasound.

Authors: Cain JA, Visagan S, Johnson MA, Crone J, Blades R, Spivak NM, Shattuck DW, Monti MM

Deep brain nuclei are integral components of large-scale circuits mediating important cognitive and sensorimotor functions. However, because they fall outside the domain of conventional non-invasive neuromodulatory techniques, their study has been primarily based on neuropsychological models, limiting the ability to fully characterize their role and to develop interventions in cases where they are damaged. To address this gap, we used the emerging technology of non-invasive low-intensity focused ultrasound (LIFU) to directly modulate left lateralized basal ganglia structures in healthy volunteers. During sonication, we observed local and distal decreases in blood oxygenation level dependent (BOLD) signal in the targeted left globus pallidus (GP) and in large-scale cortical networks. We also observed a generalized decrease in relative perfusion throughout the cerebrum following sonication. These results show, for the first time using functional MRI data, the ability to modulate deep-brain nuclei using LIFU while measuring its local and global consequences, opening the door for future applications of subcortical LIFU.

Introduction

Purpose Transcranial ultrasound stimulation
Study Objective To determine whether non-invasive low-intensity focused ultrasound (LIFU) can modulate the left globus pallidus in healthy humans and to characterize the local and global (BOLD and perfusion) effects of two sonication modes.
Animal model / Human subject Human (age: 18–44 years, sex: 15 male
Disease model Healthy
MRI or image guidance method MR image guidance (T1-weighted scans)
Targeted brain region(s) Globus Pallidus

Outcomes and Safety

Summary of Outcomes Low‑intensity focused ultrasound (LIFU) targeting the left globus pallidus produced inhibitory effects: Mode 1 elicited immediate (online) decreases in BOLD signal locally (left GP) and in distal cortical networks, while both Mode 1 and Mode 2 produced longer‑lasting (offline) widespread decreases in cerebral perfusion (ASL); Mode 2 used a PRF of 10 Hz.
Duration of biological effect 30 s
Safety-related matter No adverse events are reported; the study used low-intensity LIFU described as within intensities deemed safe for ultrasound imaging of the human cranium. The authors note potential concerns (at higher intensities) including vasoconstriction, MRI dropout, auditory/bone-conduction effects, skull-induced variability in energy deposition, and contrast LIFU with DBS risks such as hemorrhage and infection.

Brain Region

Ultrasound Parameters

Ultrasound instrument BXPulsar 1001 (Brainsonix Inc.)
FUS Frequency 0.65 MHz
FUS Intensity ISPTA: 720 mW/cm2, ISPPA: 14.40 W/cm2
FUS Pressure 1.0558 MPa
FUS Mode pulsed
Pulse duration 0.5, 5
Duration of a single FUS session 10 min
Focal Characteristics focal depth: 55 mm, aperture size: 72 mm
Treatment frequency Multiple sessions

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