Neuromodulation with Ultrasound: Hypotheses on the Directionality of Effects and Community Resource

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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

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