Rapid modulation of choice behavior by ultrasound on the human frontal eye fields

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Summary A fundamental challenge in neuroscience is establishing causal brain-function relationships with spatial and temporal precision. Transcranial ultrasonic stimulation (TUS) 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 TUS protocol targeting the frontal eye fields (FEFs) — a well-characterized circuit critical for saccadic eye movements. We demonstrate that TUS induces robust excitatory behavioral effects. Importantly, individual differences in baseline GABAergic inhibitory tone predict response magnitude. These findings establish TUS 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 TUS applications in neuroscience and clinical settings. Highlights Focused ultrasound modulates saccades with high spatial and temporal precision Inhibitory circuits in the frontal eye fields shape choice computations GABA levels predict individual variability in ultrasound-induced behavioral changes Ultrasound can be used to probe fast neural dynamics and individual differences