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Ultrasound neuromodulation hypotheses on the directionality of effects and community resource
Authors
Hugo Caffaratti, Ben Slater, Nour Shaheen, Ariane E. Rhone, Ryan Calmus, Michael E. Kritikos, Sukhbinder Kumar, Brian J. Dlouhy, Hiroyuki Oya, Timothy David Griffiths, Aaron D. Boes, Nicholas T. Trapp, Marcus Kaiser, Jérôme Sallet, Matthew I. Banks, Matthew A. Howard, Mario Zanaty, Christopher I. Petkov
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Abstract
ABSTRACT Low-intensity Transcranial Ultrasound Stimulation is a promising non-invasive technique for brain stimulation and focal neuromodulation. Research with humans and animal models has raised the possibility that TUS can be biased towards enhancing or suppressing neural function. Here, we first collate a set of hypotheses on the directionality of TUS effects and conduct an initial meta-analysis on available healthy human participant TUS studies reporting stimulation parameters and outcomes ( n = 47 studies, 52 experiments). In initial exploratory analyses with univariate tests, we find that parameters such as the intensity and continuity of stimulation (duty cycle) show statistical trends towards likely TUS neural enhancement or suppression of function. Machine-learning analyses were limited by the currently small sample size. Given that human TUS sample sizes are expected to increase, predictability on the directionality of TUS effects could improve if a database is available. Therefore, we establish an inTUS database and resource for the systematic reporting of TUS parameters and outcomes to assist in greater precision in TUS use for brain stimulation and neuromodulation. The paper concludes with a selective review of human clinical TUS studies illustrating how hypotheses on the directionality of TUS effects could be developed for empirical testing in the intended clinical application, not limited to the examples provided. Highlights Collated set of hypotheses on using TUS to bias towards neural enhancement or suppression Meta-analysis results identify parameters that may bias directionality of TUS effects inTUS resource established for systematic reporting of TUS parameters and outcomes Selective review of patient TUS studies for enhancing or suppressing neural function
Editor’s summary (commentary by The Gufo, not part of the original work)
This paper examines transcranial ultrasound stimulation (TUS), a non-invasive brain stimulation method, and whether its effects can be reliably directed towards enhancing or suppressing neural activity. The authors compiled existing hypotheses about what determines this directionality, then performed a meta-analysis of 47 human studies (52 experiments) to test which stimulation parameters—such as intensity and duty cycle—correlate with excitatory or inhibitory outcomes. Machine-learning approaches were attempted but constrained by limited data. To support future, larger-scale analyses, the team created the 'inTUS' database, a shared resource for systematically reporting TUS parameters and results. The paper closes with a review of clinical TUS studies, showing how directionality hypotheses might be tested in real therapeutic contexts, aiming to improve precision and reproducibility in future ultrasound neuromodulation research.
Why it matters: It offers a community database and meta-analytic framework that could help resolve inconsistent findings about how ultrasound brain stimulation parameters determine excitatory versus inhibitory effects.
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