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.
Data availability
The anonymized behavioral data generated in this study (trial-level tables), task timing logs, stimulation targets/coordinates, single-subject localizer peaks, and summary spectroscopy outputs with QC (i.e., the dataset required to reproduce the results reported in this paper) have been deposited in the Radboud University Data Repository under https://doi.org/10.34973/drtg-kq58. The raw MRI data are protected and are not available due to data privacy laws (GDPR) and the study’s ethics approval (CMO Oost-Nederland, CMO2022-15953). Source data are provided with this paper.
Code availability
All behavioral and fMRI task code and all analysis scripts are available at https://doi.org/10.34973/drtg-kq58.
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Acknowledgements
This experiment was supported by the Dutch Research Council (NWO), awarding VIDI fellowships to L.V. (18919) and H.E.M.d.O. (452-17-016). We would like to acknowledge Edward J. Auerbach, Ph.D., and Małgorzata Marjańska, Ph.D. (Center for Magnetic Resonance Research and Department of Radiology, University of Minnesota, USA) for the development of the pulse sequences for the Siemens platform, which were provided by the University of Minnesota under a C2P agreement. Additionally, we thank Norbert Hermesdorf, Margely Cornelissen, Hubert Voogd, Sibrecht Bouwstra, Gerard van Oijen, and Pascal de Water from the technical support group at the Donders Centre for Cognition, Faculty of Social Sciences, Radboud University, for their excellent technical assistance and support throughout this study. Finally, we would also like to thank Marwan Engels (Donders Centre for Cognition, Radboud University) for his substantial role during data acquisition, and Sjoerd Meijer (Donders Centre for Cognitive Neuroimaging, Radboud University) for his contribution to preparing the ethics documentation and to setting up the laboratory infrastructure for this study.
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S.F., L.V. and H.E.M.d.O. conceptualized and designed the experiment; A.C., S.L.Y.W. and S.F. designed and programmed the behavioral and functional localizer tasks; S.F. and S.L.Y.W. collected the data; J.P.M. set up the fMRI and MRS sequences; S.F., L.V., and H.E.M.d.O. analyzed the behavioral, functional and spectroscopy data; B.R.K. contributed to behavioral data analysis; R.S.K. contributed to spectroscopy analysis; S.L.Y.W. contributed to fMRI analysis; S.F., L.V. and H.E.M.d.O. wrote the manuscript; B.R.K., R.S.K., W.P.M., J.P.M. and A.C. revised the manuscript.
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L.V. declares no competing interests relevant to this study. L.V. is a board member of ITRUSST and the Brainbox Initiative. L.V. has received non-financial support from Image Guided Therapy SA (France), Sonic Concepts LLC (US), and Brainbox Ltd (UK), and consulting fees from Nudge LLC (US). All other authors declare no competing interests.
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Farboud, S., Kop, B.R., Koolschijn, R.S. et al. Rapid modulation of choice behavior by ultrasound on the human frontal eye fields. Nat Commun (2026). https://doi.org/10.1038/s41467-026-69854-7
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DOI: https://doi.org/10.1038/s41467-026-69854-7
