Rapid modulation of choice behavior by ultrasound on the human frontal eye fields
S. Farboud, B. R. Kop, R. S. Koolschijn, S. L. Y. Walstra, J. P. Marques, A. Chetverikov, W. P. Medendorp, L. Verhagen, H. E. M. den Ouden
Nature Communications 2026 · 10.1038/s41467-026-69854-7
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.
Abstract via europepmc.
Exposures
Exposure 1: FEF (left and right)
Target: frontal eye field — “left or right frontal eye fields (FEF)”
Device: NeuroFUS · Sonic Concepts (sold by Brainbox) · Neuro-FUS PRO system with CTX250-009 and CTX250-014 transducers ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 250 | ✓✓✓ |
| Pulse duration (ms) | 2 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 500 | ✓✓✓ |
| Duty cycle (%) | not reportedpulse duration × PRF gives 100% | ⚑ |
| Sonication duration (s) | 0.5 | ✓✓✓ |
| Free-field pressure (kPa) | 900 | ✓✓✓ |
|---|---|---|
| Free-field Isppa (W/cm²) | 25 | ✓✓✓⚑ |
| Free-field Ispta (W/cm²) | 9.37 | ✓✓✓ |
| In-situ estimate | simulation | |
| In-situ pressure (kPa) | not reported | ⚑ |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
TUS delivered for 500 ms per trial starting at onset of the first saccade target; pulse duration 2 ms with 1 ms ramp, PRF 500 Hz, pulse train duration 500 ms; sham trials consisted of the auditory mask only; left/right FEF and left/right M1 blocks counterbalanced over two TUS sessions.
Exposure 2: M1 hand area active control (left and right)
Target: primary motor cortex — “left or right hand motor cortex (M1)”
Device: NeuroFUS · Sonic Concepts (sold by Brainbox) · Neuro-FUS PRO system with CTX250-009 and CTX250-014 transducers ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 250 | ✓✓✓ |
| Pulse duration (ms) | 2 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 500 | ✓✓✓ |
| Duty cycle (%) | not reportedpulse duration × PRF gives 100% | |
| Sonication duration (s) | 0.5 | ✓✓✓ |
| Free-field pressure (kPa) | 900 | ✓✓✓ |
|---|---|---|
| Free-field Isppa (W/cm²) | 25 | ✓✓✓ |
| Free-field Ispta (W/cm²) | 9.37 | ✓✓✓ |
| In-situ estimate | simulation | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
TUS delivered for 500 ms per trial starting at onset of the first saccade target; pulse duration 2 ms with 1 ms ramp, PRF 500 Hz, pulse train duration 500 ms; sham trials consisted of the auditory mask only; left/right FEF and left/right M1 blocks counterbalanced over two TUS sessions.
Flags from extraction
exposures[0].timing.duty_cycle_pct— Duty cycle not stated. A 2 ms pulse at 500 Hz PRF (2 ms period) would be 100 %, which does not fit a ramped pulsed protocol; pulse duration and PRF recorded as written, duty cycle left not_reported.exposures[0].free_field.isppa_w_cm2— Paper gives square-wave equivalent Isppa 25 W/cm2 and an effective Isppa of 9.37 W/cm2 (ramped pulses); the 25 W/cm2 is recorded, effective value is in the quote.n_subjects— 39 enrolled; 3 excluded for eye-tracking failure and replaced, 1 further accuracy outlier; 35 analysed. Enrolled recorded.exposures[0].in_situ.pressure_kpa— Post hoc acoustic simulations were run (Fig. 2B) but no in-situ pressure or intensity value is stated in the text; only derated MI < 1.9 and delta T < 2 C.sham_type— Sham trials were auditory mask only; paper does not state whether the transducer was in place and silent, so recorded as sound_only plus the active M1 control site.