This work shows that TUS can indeed be felt, provides a roadmap for managing participant burden, and supports proper experimental blinding to enhance the validity of TUS research. Thank you to my collaborators @LennartVerhagen, @HannekedenOuden, Kim Butts Pauly, & Linda de Jong!.

Our results also provide preliminary evidence that particle displacement is a primary biophysical driving force underlying somatosensory co-stimulation. In the future, we may be able to leverage such insights to maximise CNS neuromodulatory efficacy while minimizing confounds.

While considering influence on CNS neuromodulation, we can:.Eliminate near-field intensity peaks in the scalp.Use larger aperture areas.Apply ramping.Deliver equivalent doses via longer, lower intensity pulses.Apply higher PRFs (≥200 Hz).Apply higher f0 (e.g., 500 vs 250 kHz)

How can we reduce these somatosensory confounds without compromising neuromodulation in the brain by reducing dose? Our systematic parameter mapping reveals several possible strategies:.

All participants in our study reported feeling something during TUS. Tactile sensations like 'buzzing' and 'prickling' emerged at lower doses, with thermal and painful sensations emerging as dose increased. This poses a real challenge for blinding.

We applied TUS through the temples and measured participants' somatosensory experience at the stimulation site (VAS/threshold). We tested several stimulation protocols across three different transducers to identify avenues for confound mitigation.

Hold on to your transducers TUS community! We've focused on managing what participants can hear during stimulation, but how about what they feel?! We've mapped tactile, thermal, & painful sensations during TUS - and revealed how to minimize them. Thread👇.

We speculate on why prior findings don’t replicate in our manuscript, but one thing is clear: double-blinding, TUS (& TMS) neuronavigation, and acoustic simulations are key to supporting the replicability required for TUS to truly make waves!.

For those of you now concerned about using this protocol, don't worry! There are still multiple convincing studies using 5Hz-rTUS/tbTUS with promising results, so there's no need to abandon it. Instead, let's focus our efforts on reproducibility in this quickly expanding field!.

This raises big questions:.How were such consistent excitatory effects found in prior work with variable hotspot-based targeting? Particularly considering that another independent study using 5Hz-rTUS with confirmed structural targeting reported opposite (inhibitory) effects! 🤔.

Importantly, when M1 was effectively targeted, we still didn't find evidence for offline excitatory effects!

We replicated the same TMS hotspot-based targeting approach for TUS as prior work, but by introducing post-hoc simulations we showed that this method can lead to unacceptable M1 targeting variability as compared to structurally/functionally informed targeting.

The strong & prolonged excitatory effects of 5Hz-rTUS (tbTUS) reported several times by one research group didn't replicate over APB, FDI, or ADM muscles. TUS targeting might contribute to this variability, though it cannot explain such a large discrepancy in results.

In this pre-registered study, we precisely replicated prior methodology, but added some key improvements:.- double-blinding.- TMS neuronavigation.- post-hoc acoustic simulations. TMS and EMG were used to capture intracortical and corticospinal excitability (SICI, ICF, & MEP).

Effects of 5Hz-rTUS (tbTUS) on corticospinal excitability are less robust than we initially thought. Check out my new preprint with @drcarysevans and Po-Yu Fong showing that offline excitatory TUS-TMS effects don't replicate. Thread below 👇

RT @TulikaNan: When selecting transcranial ultrasonic stimulation (TUS) parameters, what are you optimising for? The reviewers prompted us….

A big thank you to @LennartVerhagen @HannekedenOuden @tobergmann @TulikaNan @SohaFarboud @Sjoerd_Meijer_ @ARadetz @neuro_engineer @ralfer and all the co-authors!.

Moving forward, amplitude modulation (ramping), improved auditory masking, and carefully constructed (active) control conditions will form the strong foundation required for TUS to realize its full potential 🚀.

A central challenge is identifying effective and robust TUS protocols. The TUS-TMS paradigm is a common testbed in humans that has popularized the 1000 Hz and 5 Hz protocols. Such studies need proper controls to make substantiated inferences that can guide future work.

We applied TUS at 6.35-65 W/cm^2 free-water Isppa, at multiple pulse train durations, both with and without auditory masking. We controlled for the auditory confound through matched sound-sham and novel (in)active control conditions.