{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:13:27Z","timestamp":1789172007076,"version":"build-2803163510"},"posted":{"date-parts":[[2026,9,8]]},"group-title":"Neuroscience","reference-count":48,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["MH138911"],"award-info":[{"award-number":["MH138911"]}],"id":[{"id":"https:\/\/ror.org\/04xeg9z08","id-type":"ROR","asserted-by":"publisher"}]},{"award":["MH137331"],"award-info":[{"award-number":["MH137331"]}],"id":[{"id":"https:\/\/ror.org\/04xeg9z08","id-type":"ROR","asserted-by":"publisher"}]},{"award":["MH132565"],"award-info":[{"award-number":["MH132565"]}],"id":[{"id":"https:\/\/ror.org\/04xeg9z08","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"United States Department of Veterans Affairs","doi-asserted-by":"crossref","award":["RX002864"],"award-info":[{"award-number":["RX002864"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000738","name":"United States Department of Veterans Affairs","doi-asserted-by":"crossref","award":["RX005299"],"award-info":[{"award-number":["RX005299"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["GM121312"],"award-info":[{"award-number":["GM121312"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000026","name":"National Institute of Drug Abuse","doi-asserted-by":"crossref","award":["DA050989"],"award-info":[{"award-number":["DA050989"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Low-intensity focused ultrasound (LIFU) is emerging as a method for anatomically specific, noninvasive, and reversible neuromodulation of deep brain structures relevant to psychopathology. A key requirement for clinical translation is evidence of graded target engagement. We examined whether LIFU applied to deep white matter tracts produces dose-dependent functional connectivity changes in healthy adults.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    In this preregistered, double-blind, randomized study, 35 healthy adults underwent LIFU targeting (80 s, 10% duty cycle, estimated ISPPA 2.26 W\/cm\n                    <jats:sup>2<\/jats:sup>\n                    , 0.5 MHz, in a \u03b8-burst pattern) of individually modeled right thalamo-prefrontal white matter tracts under two dose conditions: one and three consecutive sonications. Dose-dependent changes in resting-state functional connectivity were examined during a 30-minute poststimulation period in 31 participants.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>One sonication acutely increased right thalamic functional connectivity with the left thalamus (28 voxels; Z = 5.48, Cohen\u2019s d = 0.61), whereas three sonications decreased connectivity with the right dorsolateral prefrontal cortex (Z = -4.05, Cohen\u2019s d = -0.45). Poststimulation time-course analysis revealed a 3-LIFU-specific linear recovery trend in the left cerebellum (Z = 4.14, d = 0.48), reflecting initial suppression followed by progressive recovery across 30 minutes. Stronger thalamo-prefrontal structural connectivity was associated with condition-specific functional connectivity changes (left frontal pole; F = 14.73, \u03b7p\u00b2 = 0.41).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These findings provide initial human evidence that LIFU is well tolerated and produces dose-dependent changes in functional connectivity associated with deep white matter tract stimulation, informing parameter selection for future circuit-based mechanistic and clinical studies.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.09.02.748985","type":"posted-content","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T22:45:15Z","timestamp":1788907515000},"source":"Crossref","is-referenced-by-count":0,"title":["Dose-Dependent Effects of Low-Intensity Focused Ultrasound on Human Deep White Matter Tracts"],"prefix":"10.64898","author":[{"given":"Aki","family":"Tsuchiyagaito","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Naresh K. 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