Broad vs narrow focus: how frequency and focal size affect transcranial ultrasound stimulation in motor cortex

Objective.Transcranial ultrasound stimulation (TUS) is a noninvasive neuromodulation technique offering millimeter-scale precision and deep targeting. However, the trade-off between fundamental frequency, focal size, and efficacy in humans remains unclear. This study aimed to compare the effects of broad versus narrow acoustic focus on corticospinal excitability using 250 kHz and 825 kHz TUS, and to evaluate whether multi-focal stimulation mitigates limitations of narrow beams.Approach.Twenty healthy adults underwent four randomized, double-blind sessions: 250 kHz unifocal, 825 kHz unifocal, 825 kHz multi-focal, and sham. TUS was delivered to the left primary motor cortex using a 128-element phased-array transducer integrated with neuronavigation. Corticospinal excitability was assessed using motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation at baseline and 5-, 30-, and 60 min post-stimulation. Reaction (RT) time and accuracy were measured using a Go/No-Go task.Main results.Linear mixed-effects modeling revealed a significant inhibition of corticospinal excitability, characterized by decreased MEP amplitudes, for both the 250 kHz unifocal and 825 kHz multi-focal conditions compared to sham (both withp= 0.018). The 825 kHz unifocal stimulation demonstrated only a non-significant trend toward inhibition (p= 0.071). Effects were transient, most evident at 5- and 30 min post-TUS. Behavioral performance (measured via RT and task accuracy) remained unchanged across all conditionsSignificance.Findings suggest that spatial coverage, achieved through broader 250 kHz beams or multi-focal cycling, is critical for effective TUS-induced neuromodulation of the motor cortex. Future studies should optimize dosing and targeting strategies to balance precision and efficacy.