Neuronavigated Repetitive Transcranial Ultrasound Stimulation Induces Long-Lasting and Reversible Effects on Oculomotor Performance in Non-human Primates

Abstract

Since the late 2010s, Transcranial Ultrasound Stimulation (TUS) has been used experimentally to carryout safe, non-invasive stimulation of the brain with better spatial resolution than Transcranial Magnetic Stimulation (TMS). This innovative stimulation method has emerged as a novel and valuable device for studying brain function in humans and animals. In particular, single pulses of TUS directed to oculomotor regions have been shown to modulate visuomotor behavior of non-human primates during 100 ms ultrasound pulses. In the present study, a sustained effect was induced by applying 20-s trains of neuronavigated repetitive Transcranial Ultrasound Stimulation (rTUS) to oculomotor regions of the frontal cortex in three non-human primates performing an antisaccade task. With the help of MRI imaging and a frame-less stereotactic neuronavigation system (SNS), we were able to demonstrate that neuronavigated TUS (outside of the MRI scanner) is an efficient tool to carry out neuromodulation procedures in non-human primates. We found that, following neuronavigated rTUS, saccades were significantly modified, resulting in shorter latencies compared to no-rTUS trials. This behavioral modulation was maintained for up to 20 min. Oculomotor behavior returned to baseline after 18-31 min and could not be significantly distinguished from the no-rTUS condition. This study is the first to show that neuronavigated rTUS can have a persistent effect on monkey behavior with a quantified return-time to baseline. The specificity of the effects could not be explained by auditory confounds.

Transient ultrasound stimulation has lasting effects on neuronal excitability

“…Conversely, ultrasound-mediated suppression of somatosensory evoked potentials peaked 5 min post-stimulation and returned to baseline within 20 min [25]. Similarly, ultrasound-mediated modulation of oculomotor behaviour was reversed within 18e31 min of stimulation [26]. These differences in temporal characteristics may be due to differences in stimulation parameters or brain regions targeted, and the fact that in vivo target regions are stimulated in a focally restricted manner, whereas our entire culture is stimulated simultaneously.…”

Combining Brain Perturbation and Neuroimaging in Non-human Primates

“…In comparison with other NIBS, however, the main advantages of FUS are its better spatial resolution and the possibility of reaching brain targets that are over several centimeters in depth from the scalp. Finally, FUS is a nonionizing technique that is relatively simple and inexpensive to implement (Elias et al, 2013;Pouget et al, 2020;Tufail et al, 2011). A basic FUS experimental setup for NHP consists of a single element ceramic transducer.…”

“…the medial frontal cortex, the somatosensory cortex, the amygdala, or the striatum) and distant regions (Folloni et al, 2019;Khalighinejad et al, 2020;Verhagen et al, 2019;Yang et al, 2018) (Figure 8B). When stimulation bursts are repeated over up to a 40 s period, neuromodulatory effects are observed offline for durations of 10 to 90 minutes (Dallapiazza et al, 2018;Folloni et al, 2019;Khalighinejad et al, 2020;Pouget et al, 2020;Verhagen et al, 2019). In vitro results suggest that TUS effects could even last for up to 8-14 hours (Clennell et al, 2021).…”

Social prediction modulates activity of macaque superior temporal cortex

“…As a control region, we stimulated the ACC which is involved in the extended social brain. The impact of TUS on FEF and ACC and their consequence on behavior have already been demonstrated 41,[52][53][54] . We also collected control data for which no stimulation was performed (note that these are the data used in the replication).…”

“…To assess if attentional or oculomotor related neural activity could explain the modulation by social prediction in the SPA, we performed Transcranial Ultrasound Stimulation (TUS) on the same macaques used for the replication just prior to the fMRI free-viewing task. We stimulated the Frontal Eye Field (FEF) as it is involved in attention and oculomotor movement such as saccades 52,53 , and was also revealed in our social prediction analysis. As a control region, we stimulated the ACC which is involved in the extended social brain.…”