{"doi":"10.1016/j.brs.2023.03.002","title":"Auditory Mondrian masks the airborne-auditory artifact of focused ultrasound stimulation in humans","abstract":"Low-intensity Focused Ultrasound Stimulation (FUS) can modulate neural activity in cortical, subcortical, and deep brain regions, achieving millimeter precision through transcranial ultrasound stimulation (TUS) and can affect behavior [[1]Rabut C. Yoo S. Hurt R.C. Jin Z. Li H. Guo H. et al.Ultrasound technologies for imaging and modulating neural activity.Neuron. 2020; 108: 93-110Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar,[2]Rezayat E. Toostani I.G. A review on brain stimulation using low intensity focused ultrasound.Basic Clin Neurosci. 2016; 7: 187-194PubMed Google Scholar]. However, there is concern that FUS may induce an auditory effect, cortically activating the subject's auditory sensation, thus confounding behavioral and electrophysiological responses during TUS research [3Guo H. Hamilton Ii M. Offutt S.J. Gloeckner C.D. Li T. Kim Y. et al.Ultrasound produces extensive brain activation via a cochlear pathway.Neuron. 2018; 99: 866Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar, 4Sato T. Shapiro M.G. Tsao D.Y. Ultrasonic neuromodulation causes widespread cortical activation via an indirect auditory mechanism.Neuron. 2018; 98: 1031-10341 e5Abstract Full Text Full Text PDF PubMed Scopus (169) Google Scholar, 5Johnstone A. Nandi T. Martin E. Bestmann S. Stagg C. Treeby B. A range of pulses commonly used for human transcranial ultrasound stimulation are clearly audible.Brain Stimul. 2021; 14: 1353-1355Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar, 6Braun V. Blackmore J. Cleveland R.O. Butler C.R. Transcranial ultrasound stimulation in humans is associated with an auditory confound that can be effectively masked.Brain Stimul. 2020; 13: 1527-1534Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar, 7Park C. Chen M. Kim T. Implication of auditory confounding in interpreting somatosensory and motor responses in low-intensity focused transcranial ultrasound stimulation.J Neurophysiol. 2021; 125: 2356-2360Crossref PubMed Scopus (5) Google Scholar]. Several studies have mitigated this auditory artifact through ramping [[8]Mohammadjavadi M. Ye P.P. Xia A. Brown J. Popelka G. Pauly K.B. Elimination of peripheral auditory pathway activation does not affect motor responses from ultrasound neuromodulation.Brain Stimul. 2019; 12: 901-910Abstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar] or audio masking [[5]Johnstone A. Nandi T. Martin E. Bestmann S. Stagg C. Treeby B. A range of pulses commonly used for human transcranial ultrasound stimulation are clearly audible.Brain Stimul. 2021; 14: 1353-1355Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar,[6]Braun V. Blackmore J. Cleveland R.O. Butler C.R. Transcranial ultrasound stimulation in humans is associated with an auditory confound that can be effectively masked.Brain Stimul. 2020; 13: 1527-1534Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar], but prior research has had two main limitations. First, previous studies addressed a limited range of the total FUS parameter space: fundamental frequency (f0), pulse repetition frequency (PRF), duty cycle (DC), sonication duration (SD), and intensity (I) [[1]Rabut C. Yoo S. Hurt R.C. Jin Z. Li H. Guo H. et al.Ultrasound technologies for imaging and modulating neural activity.Neuron. 2020; 108: 93-110Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar,[7]Park C. Chen M. Kim T. Implication of auditory confounding in interpreting somatosensory and motor responses in low-intensity focused transcranial ultrasound stimulation.J Neurophysiol. 2021; 125: 2356-2360Crossref PubMed Scopus (5) Google Scholar,9Younan Y. Deffieux T. Larrat B. Fink M. Tanter M. Aubry J.F. Influence of the pressure field distribution in transcranial ultrasonic neurostimulation.Med Phys. 2013; 40082902Crossref PubMed Scopus (131) Google Scholar, 10King R.L. Brown J.R. Newsome W.T. Pauly K.B. 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