ORCID

Abstract

INTRODUCTION: Transcranial ultrasound stimulation (TUS) shows great promise for inducing neuroplastic changes that persist long after stimulation. Evidence of stimulation-locked (online) neural changes would enable the development of closed-loop application of TUS. However, such responses have been difficult to distinguish from coincident neural activity caused by auditory and somatosensory effects of TUS.

METHODS: To dissociate genuine online neuromodulatory effects from peripheral confounds, we leveraged the contralateral retinotopic organization of the early visual cortex in nineteen subjects. Using a hemifield visual stimulation paradigm combined with high-precision, functional MRI-guided TUS, we applied TUS to the left early visual cortex while participants viewed checkerboards presented in the left or right visual hemifield. Randomized delivery of TUS on half of the trials enabled within-subject comparisons of hemisphere-specific, pattern-locked visual evoked potentials (VEPs) across stimulated and unstimulated hemispheres, as well as across visual-stimulus and no-stimulus conditions.

RESULTS: TUS to the left visual cortex reduced mean VEP amplitude over the stimulated (left) hemisphere for right-hemifield (contralateral) stimuli. No such reduction appeared at the symmetric right-hemisphere sites for left-hemifield stimuli. The degree of online suppression correlated positively with target engagement, estimated by modelling the TUS field that accounted for inter-individual heterogeneity in skull transmission and its overlap with the fMRI-defined target. This relationship suggests that greater target engagement is reliably associated with stronger TUS-induced neural modulation.

CONCLUSIONS: These findings provide clear evidence of online, spatially specific TUS-induced neural modulation, dissociated from peripheral confounds. This approach establishes a robust framework for future studies aiming to map the TUS parameter space in real time by leveraging topographic organization to control for peripheral confounds, and supports the development of closed-loop neuromodulation protocols.

Publication Date

2026-03-01

Publication Title

Brain Stimulation

Volume

19

Issue

2

ISSN

1935-861X

Acceptance Date

2025-12-31

Deposit Date

2026-03-24

Funding

Pump Priming Funds from the School of Psychology and from the Bain Research Imaging Centre, University of Plymouth (SD). UK Research and Innovation, Future Leaders Fellowship grant MR/Y034368/1 (EF). Biotechnology and Biological Sciences Research Council grant BB/Y001494/1 (EF). Engineering and Physical Sciences Research Council, Neuromod + Programme grant EP/W035057/1 (EF). Advanced Research and Invention Agency grant SCNI-PR01-P15 (EF).

Keywords

Neuromodulation, Non-invasive brain stimulation, Online, Real-time, Transcranial ultrasound stimulation, Visual cortex, Visual evoked potentials, Visual Perception/physiology, Humans, Male, Functional Laterality/physiology, Young Adult, Visual Cortex/physiology, Magnetic Resonance Imaging, Evoked Potentials, Visual/physiology, Female, Adult, Photic Stimulation

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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