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 effect polarity, size, and spatial specificity have been difficult to assess. Here, we engaged non-human primates (macaca mulatta) in an established task that provides a well defined framework to characterize the neuromodulatory effects. 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 effect 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 effects suggested a neuronal excitation within the stimulated regions. No effects 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, double-dissociated effects 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.