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.

Transcranial ultrasound stimulation of the human motor cortex

“…Cain et al. investigated the effect of a 10-min session of rTUS on the left globus pallidus in humans and observed decreased blood oxygenation level-dependent (BOLD) signals in local and distal brain regions ( Cain et al., 2021 ). However, previous studies mainly aim to investigate cognitive brain function change but not to explore the cortical plasticity change and the duration of aftereffects, which are essential for the clinical translation of rTUS intervention.…”

Mapping the subcortical connectivity of the human default mode network

“…Anti-correlations reflect numerous neurovascular-glial properties (Fox et al, 2009;He et al, 2018), and thus our anti-correlation results do not provide direct proof of the mesocircuit hypothesis. Nevertheless, our rs-fMRI methods provide a mesoscale biomarker of mesocircuit integrity that may have utility in clinical trials, particularly when considering that non-invasive stimulation techniques such as LIFUP are now targeting the globus pallidus (Cain et al, 2021b) and central thalamus (Cain et al, 2021a;Monti et al, 2016) in patients with disorders of consciousness.…”

“…Testing for functional connectivity between subcortical regions and cortical DMN thus provides an opportunity to identify subcortical therapeutic targets in patients with DoC. Many such targets are amenable to therapeutic modulation by electromagnetic (Elias et al, 2020;Gratwicke et al, 2013;Kakusa et al, 2020;Schiff et al, 2007) and ultrasound-based therapies (Cain et al, 2021a(Cain et al, , 2021bMonti et al, 2016). However, DMN subcortical connectivity has not been fully mapped.…”

“…The biological and mechanistic rationale for this targeted approach to neuromodulation has been demonstrated in rodent (Taylor et al, 2016) and non-human primate (Redinbaugh et al, 2020) models, which show that stimulation of subcortical network hubs promotes cortical reactivation and reemergence of consciousness from anesthetic coma. Emerging evidence from human electrical (Corazzol et al, 2017;Schiff et al, 2007;Thibaut et al, 2014), pharmacologic (Giacino et al, 2012;Whyte et al, 2014), and ultrasound-based (Cain et al, 2021a(Cain et al, , 2021bMonti et al, 2016) stimulation studies provide proof of principle that promoting recovery of consciousness in patients with DoC is possible (Edlow et al, 2021a). However, consensus on optimal subcortical therapeutic targets for neuromodulation of consciousness in humans has not been established (Edlow et al, 2021b).…”

Toward focused ultrasound neuromodulation in deep brain stimulator implanted patients: Ex-vivo thermal, kinetic and targeting feasibility assessment

“…Dear Editor, Non-invasive transcranial ultrasound (TUS) neuromodulation is an emerging technique that has been demonstrated as safe in humans for cortical [1][2][3][4][5] and subcortical [6,7] targets. Deep brain stimulation (DBS) systems with local field potential (LFP) recording ability [8] might be utilized to record TUS-induced LFP changes and acoustic pressure induced artefact in the LFP recordings can be regarded as an evidence of engagement of acoustic waves with the target.…”