Abstract A fundamental challenge in neuroscience is establishing causal brain-function relationships with spatial and temporal precision. Transcranial ultrasonic stimulation offers a unique opportunity to modulate deep brain structures non-invasively with high spatial resolution, but temporally precise effects and their neurophysiological foundations have yet to be demonstrated in humans. Here, we develop a temporally precise ultrasound stimulation protocol targeting the frontal eye fields — a well-characterized circuit critical for saccadic eye movements. We demonstrate that ultrasonic stimulation induces robust excitatory behavioral effects. Importantly, individual differences in baseline GABAergic inhibitory tone predict response magnitude. These findings establish ultrasound stimulation as a reliable tool for chronometric circuit interrogation and highlight the importance of neurophysiological state in neuromodulation. This work bridges human and animal research, advancing targeted transcranial ultrasonic stimulation applications in neuroscience and clinical settings.
Farboud et al. (Fri,) studied this question.