Broad vs narrow focus: how frequency and focal size affect transcranial ultrasound stimulation in motor cortex
Ali K Zadeh, Alan Coreas, Shirshak Shrestha, Iris Kathol, Davide Martino, G Bruce Pike, Samuel Pichardo, Oury Monchi
Journal of Neural Engineering 2026, 23, 036031 · 10.1088/1741-2552/ae730a
Abstract
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 with p = 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 conditions Significance. 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.
Abstract via europepmc.
Exposures
Exposure 1: 250 kHz unifocal (250-UF)
Target: primary motor cortex — “left primary motor cortex (M1), hand-knob/precentral gyrus hotspot”
Device: Sonic Concepts · Sonic Concepts · H317 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 250 | ✓✓✓ |
| Pulse duration (ms) | not reportedimplied by duty cycle ÷ PRF: 1 ms (not stated by the paper) | |
| Pulse repetition frequency (Hz) | 100 | ✓✓✓ |
| Duty cycle (%) | 10 | ✓✓✓ |
| Sonication duration (s) | 120 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | simulationmean or range across subjects | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | 3.25 | ✓✓✓ |
| In-situ Ispta (W/cm²) | 0.5 | ✓✓✓⚑ |
TUS delivered to left M1 at PRF 100 Hz, duty cycle 10%, for 120 s; a total ramp of 25% of the burst duration (12.5% up, 12.5% down) was applied to minimise onset artifacts. MEPs (30 TMS pulses at 120% RMT) and RT/accuracy were assessed at baseline and 5, 30, 60 min post-TUS.
Exposure 2: 825 kHz unifocal (825-UF) and multi-focal (825-MF)
Target: primary motor cortex — “left primary motor cortex (M1), hand-knob/precentral gyrus hotspot”
Device: Sonic Concepts · Sonic Concepts · H317 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 825 | ✓✓✓ |
| Pulse duration (ms) | not reportedimplied by duty cycle ÷ PRF: 1 ms (not stated by the paper) | |
| Pulse repetition frequency (Hz) | 100 | ✓✓✓ |
| Duty cycle (%) | 10 | ✓✓✓ |
| Sonication duration (s) | 120, 360swept | ✓✓✓⚑ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | simulationmean or range across subjects | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | 4.02, 3.38swept | ✓✓✓⚑ |
| In-situ Ispta (W/cm²) | 0.5 | ✓✓✓ |
825 kHz unifocal TUS delivered for 120 s at PRF 100 Hz, duty cycle 10%. The 825 kHz multi-focal condition electronically cycled three simultaneous foci sequentially (2 s intervals) so each focus received 120 s of effective stimulation, extending total session duration to 360 s; same PRF/duty-cycle/ramping as the unifocal conditions.
Flags from extraction
sham_type— Sham was implemented by electronically defocusing the ultrasound (randomized phase settings) rather than an inactive/powered-off transducer, active control site, or sound-only sham; does not cleanly match a listed sham_type category, coded as 'other'.exposures[1].timing.sonication_duration_s— 825 kHz unifocal (120 s) and multi-focal (360 s total, 120 s effective per focus) sessions are combined into one exposure per the target x frequency rule, though they differ in focal pattern (single vs three cycled foci) in addition to duration.exposures[1].in_situ.isppa_w_cm2— List combines the separately reported Table 1 mean adjusted in situ ISPPA for the 825 kHz unifocal (4.02 W/cm2) and multi-focal (3.38 W/cm2) sessions.exposures[0].in_situ.ispta_w_cm2— 0.5 W/cm2 is the initially intended common in situ ISPTA target stated for all sessions before per-participant safety adjustment; Table 1 only reports adjusted ISPPA (not ISPTA) per session, so the intended value is used here.