Alteration of functional connectivity in the cortex and major brain networks of non-human primates following focused ultrasound exposure.
Authors: Liu D, Munoz F, Sanatkhani S, Pouliopoulos AN, Konofagou E, Grinband J, Vp F
Focused ultrasound (FUS) is a non-invasive neuromodulation technology that is being investigated for potential treatment of neurological and psychiatric disorders. Focused ultrasound combined with microbubbles can temporarily open the intact blood-brain barrier (BBB) of animals and humans, and facilitate drug delivery. FUS exposure, either with or without microbubbles, has been demonstrated to alter the behavior of non-human primates, and previous work has demonstrated transient and long-term effects of FUS neuromodulation on functional connectivity using resting state functional MRI. However, it is unknown whether opening the BBB affects functional connectivity differently than FUS alone. Thus we applied FUS alone (neuromodulation) and FUS with microbubbles (BBB opening) in the dorsal striatum of lightly anesthetized non-human primates, and compared changes in functional connectivity in major brain networks. We found different alteration patterns between FUS neuromodulation and FUS-mediated BBB opening in several cortical areas, and we also found that applying FUS to a deep brain structure can alter functional connectivity in the default mode network and frontotemporal network.
Introduction
Purpose
Transcranial ultrasound stimulation
Study Objective
Compare how FUS neuromodulation versus FUS-mediated BBB opening in the dorsal striatum of non-human primates differentially alter resting-state functional connectivity of major brain networks.
Animal model / Human subject
Non human primates
MRI or image guidance method
MRI-guided (MRgFUS)
Targeted brain region(s)
Striatum
Outcomes and Safety
Summary of Outcomes
Focused ultrasound targeted to the right caudate produced distinct neuromodulatory effects: FUS alone increased caudate–insular connectivity and decreased caudate–motor connectivity, whereas FUS combined with microbubbles (BBB opening) increased caudate–medial prefrontal and frontotemporal network connectivity
Safety-related matter
Numerical simulations and measurements indicated temperature elevations (skull up to 41.2°C, muscle 39.7°C, brain 38.2°C; ~3–4°C above baseline) and peak negative pressure >800 kPa, with maximum temperatures stated to be within current safety guidelines. No adverse effects were reported in the study.
Brain Region
Ultrasound Parameters
Ultrasound instrument
Single-element focused ultrasound transducer (H-107, Sonic Concepts)
FUS Frequency
500 kHz
FUS Pressure
800 kPa (FUS neuromodulation); 400 kPa (FUS and microbubbles)
FUS Mode
pulsed
Pulse duration
10 ms
Duration of a single FUS session
2 minutes
Focal Characteristics
focal depth: None; focal length: None; aperture size: None
Treatment frequency
single session
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