{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T23:31:23Z","timestamp":1770679883330,"version":"3.49.0"},"posted":{"date-parts":[[2026,1,30]]},"group-title":"Bioengineering","reference-count":11,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"NIH","award":["T32GM008042"],"award-info":[{"award-number":["T32GM008042"]}]},{"name":"NIH","award":["F30MH136802"],"award-info":[{"award-number":["F30MH136802"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,1,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Transcranial focused ultrasound (tFUS) is an emerging noninvasive neuromodulation modality with the ability to target deep brain structures with high spatial precision. Despite its promise, rigorous evaluation of its efficacy is limited by the absence of reliable, fully double-blind sham methodologies.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To develop and validate a pair of visually and mechanically indistinguishable acoustic coupling pads that enable true double-blind tFUS neuromodulation studies by providing either efficient ultrasound transmission or robust ultrasound blocking without altering participant or operator experience.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Two coupling pads were engineered: a transmitting pad designed to allow &lt;5% pressure amplitude loss relative to free-water propagation, and a non-transmitting pad designed to attenuate ultrasound by \u226540 dB. Both pads used a Dragon Skin 10 NV silicone base and were identical in size, appearance, flexibility, and handling. The non-transmitting pad incorporated an encapsulated air-based blocking layer using an open-cell polyethylene foam insert. Acoustic performance was evaluated in a water tank using a 650 kHz BrainSonix transducer and a calibrated needle hydrophone. Sound speed of the silicone material was measured using pulse-echo techniques.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Twenty-three matched transmitting and non-transmitting pad pairs were fabricated and tested. Transmitting pads demonstrated a mean attenuation of \u22120.41 \u00b1 0.53 dB, satisfying the design criterion of minimal acoustic loss.Non-transmitting pads demonstrated a mean attenuation of \u221248.61 \u00b1 4.33 dB, exceeding the required \u221240 dB threshold for effective sham conditions. The Dragon Skin 10 NV substrate exhibited a sound speed of 964.72 m\/s and produced &lt;2 mm axial focal shift for standard pad thicknesses, with no measurable change in focal width. Both pad types were visually and tactually indistinguishable, could not be differentiated by experienced operators or participants, and maintained mechanical integrity after repeated cleaning<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>These acoustically engineered coupling pads provide a practical and validated solution for achieving true single- and double-blind conditions in tFUS neuromodulation studies. By preserving identical sensory and procedural experiences while enabling precise control over ultrasound transmission, this approach addresses a critical methodological gap in human ultrasound neuromodulation research.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.01.27.702113","type":"posted-content","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T23:10:31Z","timestamp":1769814631000},"source":"Crossref","is-referenced-by-count":0,"title":["Development of Visually Indistinguishable Acoustic Coupling Pads for Double-Blind Focused Ultrasound Neuromodulation Studies"],"prefix":"10.64898","author":[{"given":"Samantha F.","family":"Schafer","sequence":"first","affiliation":[{"name":"School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2386-2987","authenticated-orcid":false,"given":"Norman M.","family":"Spivak","sequence":"additional","affiliation":[{"name":"Department of Psychiatry & Biobehavioral Sciences, UCLA, 760 Westwood Plaza, Suite C8-519, Los Angeles, CA 90095, United States"},{"name":"Department of Neurosurgery, UCLA, 760 Westwood Plaza, Suite C8-519, Los Angeles, CA 90095, United States"},{"name":"UCLA-Caltech Medical Scientist Training Program"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7854-3763","authenticated-orcid":false,"given":"Andrew A.E.D.","family":"Bishay","sequence":"additional","affiliation":[{"name":"Department of Psychiatry & Biobehavioral Sciences, UCLA, 760 Westwood Plaza, Suite C8-519, Los Angeles, CA 90095, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Bystritsky","sequence":"additional","affiliation":[{"name":"Department of Psychiatry & Biobehavioral Sciences, UCLA, 760 Westwood Plaza, Suite C8-519, Los Angeles, CA 90095, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter A.","family":"Lewin","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0832-8695","authenticated-orcid":false,"given":"Mark E.","family":"Schafer","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"issue":"4","key":"2026020512190767000_2026.01.27.702113v1.1","doi-asserted-by":"crossref","first-page":"501","DOI":"10.4103\/0974-2700.86646","article-title":"Clinical ultrasound physics","volume":"4","year":"2011","journal-title":"Journal of Emergencies, Trauma, and Shock"},{"key":"2026020512190767000_2026.01.27.702113v1.2","unstructured":"Kinsler LE , Frey AR , Coppens AB , Sanders JV . Fundamentals of acoustics. John wiley & sons; 2000."},{"key":"2026020512190767000_2026.01.27.702113v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2010.02.005"},{"key":"2026020512190767000_2026.01.27.702113v1.4","doi-asserted-by":"publisher","DOI":"10.3389\/fnhum.2020.00052"},{"issue":"6","key":"2026020512190767000_2026.01.27.702113v1.5","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1016\/j.brs.2020.10.007","article-title":"Sonication of the anterior thalamus with MRI-Guided transcranial focused ultrasound (tFUS) alters pain thresholds in healthy adults: A double-blind, sham-controlled study","volume":"13","year":"2020","journal-title":"Brain Stimul"},{"issue":"5","key":"2026020512190767000_2026.01.27.702113v1.6","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1016\/j.ultrasmedbio.2021.01.025","article-title":"Transcranial Focused Ultrasound Enhances Sensory Discrimination Capability through Somatosensory Cortical Excitation","volume":"47","year":"2021","journal-title":"Ultrasound in Medicine and Biology"},{"issue":"6","key":"2026020512190767000_2026.01.27.702113v1.7","doi-asserted-by":"crossref","first-page":"1923","DOI":"10.1109\/TBME.2020.3030892","article-title":"Transcranial Focused Ultrasound Neuromodulation of Voluntary Movement-Related Cortical Activity in Humans","volume":"68","year":"2021","journal-title":"IEEE Transactions on Biomedical Engineering"},{"key":"2026020512190767000_2026.01.27.702113v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-28320-1"},{"issue":"6","key":"2026020512190767000_2026.01.27.702113v1.9","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1016\/j.brs.2020.08.014","article-title":"Transcranial ultrasound stimulation in humans is associated with an auditory confound that can be effectively masked","volume":"13","year":"2020","journal-title":"Brain Stimul"},{"key":"2026020512190767000_2026.01.27.702113v1.10","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.23931"},{"issue":"4","key":"2026020512190767000_2026.01.27.702113v1.11","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1016\/j.brs.2021.06.003","article-title":"Safety of focused ultrasound neuromodulation in humans with temporal lobe epilepsy","volume":"14","year":"2021","journal-title":"Brain Stimul"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.01.27.702113","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T20:19:17Z","timestamp":1770322757000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.01.27.702113"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,30]]},"references-count":11,"URL":"https:\/\/doi.org\/10.64898\/2026.01.27.702113","relation":{},"subject":[],"published":{"date-parts":[[2026,1,30]]},"subtype":"preprint"}}