Real Time and Delayed Effects of Subcortical Low Intensity Focused Ultrasound

Abstract

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.

Disruptions in effective connectivity within and between default mode network and anterior forebrain mesocircuit in prolonged disorders of consciousness

“…Beyond the above discussed changes in self-inhibition, we did not identify any differences in the region-to-region connections of the DMN in PDOC. This is in contrast with previous studies reporting differences in functional connectivity between PDOC and healthy controls, many of which consistently reported disconnections between midline DMN regions [2,54,60,61]. These typically correlate with level of consciousness (based on CRS-R score) and outcome [62].…”

“…Previous research suggests that structural differences are more prominent in the left hemisphere in PDOC [51,52], and atrophy in the left thalamus predicts functional outcome in post-traumatic brain injury survivors [53]. Furthermore, the metabolic integrity of the left hemisphere better predicts clinical diagnosis (vegetative versus minimally conscious state) [54]. In a recent ultrasound stimulation study in 3 chronic PDOC patients, stimulation of the left thalamus elicited some promising improvements in CRS-R scores [55].…”

A causal role of anterior prefrontal-putamen circuit for response inhibition revealed by transcranial ultrasound stimulation in humans

“…In the present study, low-intensity transcranial ultrasound stimulation (TUS) was used to perform interventions in the human basal ganglia. TUS can noninvasively stimulate the deep brain structures with high spatial accuracy of a few millimeters (Cain et al, 2021;Darmani et al, 2022;Folloni et al, 2019;Fomenko et al, 2018;Fouragnan et al, 2019;Kubanek et al, 2020;Legon et al, 2014;Pasquinelli et al, 2019). Previous studies have reported that TUS can induce short-or long-term suppression/enhancement of the activity depending on stimulation protocols (Fomenko et al, 2020;Legon et al, 2018;Verhagen et al, 2019;Zeng et al, 2022;Zhang et al, 2021).…”

Noninvasive Brain Stimulation Therapies to Promote Recovery of Consciousness: Where We Are and Where We Should Go

“…While the exact focality of LIFU depends on several factors including the technology, specific settings, depth of the chosen focus, and the skull properties, when aiming at deep brain structures the area of maximal stimulation is approximately 0.5 cm radially by approximately 1.25 cm longitudinally. 61 Focused ultrasound can exert bioactivity through multiple mechanisms including thermogenic effects, cavitation, and mechanical agitationthe first two are typical of nonreversible, ablative, highintensity focused ultrasound (HIFU), a technique typically used for noninvasive surgery. 62 At the intensities typical of LIFU, reversible and nondamaging mechanical agitation appears to be the primary mechanism for bioactivity.…”