Transcranial ultrasound selectively biases decision-making in primates

Abstract

Transcranial focused ultrasound has the promise to evolve into a transformative noninvasive way to modulate activity of neuronal circuits deep in the brain. The approach may enable systematic and causal mapping of how individual brain circuits are involved in specific behaviors and behavioral disorders. Previous studies demonstrated neuromodulatory potential, but the e↵ect polarity, size, and spatial specificity have been di cult to assess. Here, we engaged non-human primates (macaca mulatta) in an established task that provides a well defined framework to characterize the neuromodulatory e↵ects. In this task, subjects decide whether to look at a right or a left target, guided by one the targets appearing first. Previous studies showed that excitation/inhibition of oculomotor circuits leads to contralateral/ipsilateral biases in this choice behavior. We found that brief, low-intensity ultrasound stimuli (300 ms, 0.6 MPa, 270 kHz) delivered to the animals' left/right frontal eye fields bias the animals' decisions to the right/left visual hemifield. The e↵ect was modest, about on the order of that produced when injecting moderate amounts of potent neuromodulatory drugs into the same regions in this task. The polarity of the e↵ects suggested a neuronal excitation within the stimulated regions. No e↵ects were observed when we applied the same stimuli to control brain regions not involved in oculomotor target selection. Together, using an established paradigm, we found that transcranial ultrasound is capable of modulating neurons to the extent of biasing choice behavior of non-human primates. A demonstration of tangible, brain-region-specific e↵ects on behavior of primates constitutes a critical step toward applying this noninvasive neuromodulation method in investigations of how specific neural circuits are involved in specific behaviors or disease signs. Sato et al., 2018). In these studies, applications of low-intensity stimuli to peri-motor regions often lead to visible movements of the limbs or other body parts. There have been concerns that the small size of the rodent brain, relative to the dimensions of the focal spot, results in reflections, Li

Spherical Array System for High-Precision Transcranial Ultrasound Stimulation and Optoacoustic Imaging in Rodents

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Membrane Charge Oscillations During Ultrasonic Neuromodulation by Intramembrane Cavitation

“…U LTRASONIC neuromodulation (UNMOD) has gained significant attention in the last decade, because of its capability to modulate brain activity reversibly, non-invasively, selectively, and with high spatial resolution (transversal fullwidth at half maximum in the order of millimeters with a single element focused transducer) [1]- [15]. Furthermore, a good safety profile has been reported [16], [17] and there is no requirement to genetically alter target neurons (cfr.…”

Effect of Low Intensity Transcranial Ultrasound Stimulation on Neuromodulation in Animals and Humans: An Updated Systematic Review

“…Behavioral data revealed that targeting the left FEF increased the proportion of rightward choices, whereas, stimulation of the right FEF increased the proportion of leftward choices. As an active control, region-specific LI-TUS applied at M1 failed to elicit significant biases in choice behavior (Kubanek et al, 2020).…”