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.
Highlights
Transcranial Ultrasound Stimulation (TUS) is a safe, focused and non-invasive method of brain stimulation that has emerged as a novel and valuable tool for studying brain function in humans and animals
We present a detailed account of the effects of repetitive Transcranial Ultrasound Stimulation on the oculomotor regions of awake macaque monkeys while the animals were performing an antisaccade task
Monkey L and monkey G presented significantly higher error rates on the ipsilateral side of the frontal eye fields (FEF)/supplementary eye fields (SEF) stimulation. These increases in error were very low, suggesting that the animals were performing the task uniformly during both repetitive Transcranial Ultrasound Stimulation (rTUS) and no-rTUS sessions. It suggests that rTUS did not disturb the animals’ general performance when either the frontal or the primary cortices were the targets of the neurostimulation
Summary
Transcranial Ultrasound Stimulation (TUS) is a safe, focused and non-invasive method of brain stimulation that has emerged as a novel and valuable tool for studying brain function in humans and animals. Our group has shown in awake non-human primates that single pulses of TUS can modulate visuomotor behavior (Deffieux et al, 2013) with brief modulating effects (∼100 ms) from TUS in single neuronal responses (Wattiez et al, 2017) Whether such modulations due to TUS can be temporally extended and controlled remains to be demonstrated. If the TMS effect on the performance of a certain behavioral task is known, this task can serve as a “functional” probe to position the coil with subsequent targets or tasks (Göbel et al, 2001) Such “hunting” procedures can, be time-consuming due to the fact that different locations need to be tested by trial-and-error. The interpretation of the results with respect to brain anatomy is limited by the fact that the coil position is determined functionally and not anatomically
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