Offline impact of transcranial focused ultrasound on cortical activation in primates

Abstract

To understand brain circuits it is necessary both to record and manipulate their activity. Transcranial ultrasound stimulation (TUS) is a promising non-invasive brain stimulation technique. To date, investigations report short-lived neuromodulatory effects, but to deliver on its full potential for research and therapy, ultrasound protocols are required that induce longer-lasting ‘offline’ changes. Here, we present a TUS protocol that modulates brain activation in macaques for more than one hour after 40 s of stimulation, while circumventing auditory confounds. Normally activity in brain areas reflects activity in interconnected regions but TUS caused stimulated areas to interact more selectively with the rest of the brain. In a within-subject design, we observe regionally specific TUS effects for two medial frontal brain regions – supplementary motor area and frontal polar cortex. Independently of these site-specific effects, TUS also induced signal changes in the meningeal compartment. TUS effects were temporary and not associated with microstructural changes.

Transcranial Focused Ultrasound to the Right Prefrontal Cortex Improves Mood and Alters Functional Connectivity in Humans

“…Corresponding connectivity changes in networks relevant for emotion/mood regulation occurred 20 min after sonication in Experiment 2, demonstrating that tFUS could modulate functionally specific brain networks relevant for mood regulation. These results are in line with recent experiments suggesting that tFUS can modulate network connectivity (Folloni et al, 2019;Verhagen et al, 2019). These results are the first to demonstrate that tFUS can affect mood and cortical networks important for mood regulation, with effects that appear on the order of 20 min following tFUS delivery.…”

Two fiber pathways connecting amygdala and prefrontal cortex in humans and monkeys

“…The importance of considering neural circuitry, extending beyond individual brain regions, is increasingly evident when studying the contributions of ventral PFC in emotion, learning, and decision-making. Combining controlled focal lesion and transient perturbation studies with wholebrain neuroimaging highlights the critical role of remote connections to the impact of local perturbations Froudist-Walsh et al, 2018;Verhagen et al, 2019). Moreover, it has recently been demonstrated that some lesion effects might be better explained by damage to connections as opposed to damage to single regions (Rudebeck et al, 2013;Thiebaut de Schotten and Foulon, 2018) and differences in connectivity have already been argued to play a crucial role in regional specialization in other brain areas (Krubitzer, 2007).…”

Repeated Application of Transcranial Diagnostic Ultrasound Towards the Visual Cortex Induced Illusory Visual Percepts in Healthy Participants

“…In a primate model, Folloni et al (2019), discussed above, used nDU to create comparable effects that lasted more than an hour. Verhagen et al (2019) demonstrated even longer-lasting effects from nDU stimulation. Using a 40 s nDU stimulation protocol applied to the supplementary motor area of macaques, they found regionally specific modulatory effects lasting up to 2 h after stimulation relative to controls.…”