{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:11:56Z","timestamp":1786119116535,"version":"build-2736575974"},"reference-count":36,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Key R&D Program of China","award":["2024YFC2707800"],"award-info":[{"award-number":["2024YFC2707800"]}]},{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82501843"],"award-info":[{"award-number":["82501843"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Major depressive disorder (MDD) is highly prevalent in adolescents, and a substantial proportion of patients show inadequate response or limited tolerability to first-line treatments such as selective serotonin reuptake inhibitors and cognitive behavioral therapy, highlighting the need for additional treatment options. Repetitive transcranial magnetic stimulation (rTMS) has demonstrated efficacy in adults with depression, but evidence in adolescents remains limited. Resting-state functional connectivity MRI (rs-fcMRI) may provide a circuit-informed approach for individualizing rTMS target selection within the dorsolateral prefrontal cortex (DLPFC) based on its functional connectivity with the subgenual anterior cingulate cortex (sgACC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This is a randomized, double-blind, three-arm, sham-controlled pilot trial. Forty-five adolescents with MDD will be assigned in a 1:1:1 ratio to conventional left DLPFC-targeted rTMS, rs-fcMRI-guided rTMS targeting the individualized DLPFC site showing the strongest negative connectivity with the sgACC, or sham stimulation. Treatment will be delivered over 4 weeks. Primary outcomes will include recruitment feasibility, intervention adherence, 6-month retention, preliminary clinical efficacy, and safety, assessed by enrollment, completion of 20 treatment sessions, completion of 6-month follow-up, CDRS-R-based response and remission, and adverse events\/serious adverse events. Secondary outcomes will include depressive and anxiety symptoms, suicidality, sleep quality, global clinical status and improvement, rumination, and pediatric health-related quality of life.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This pilot trial will provide preliminary evidence regarding the feasibility, acceptability, safety, and early clinical efficacy signals of rs-fcMRI-guided rTMS in adolescents with MDD. By comparing individualized circuit-informed targeting with conventional left DLPFC stimulation and sham stimulation, the study may help clarify whether this imaging-guided neuromodulation approach is practicable and clinically informative in this population. The findings are expected to support refinement of study procedures, outcome selection, and trial design for a future fully powered randomized controlled trial.<\/jats:p>\n                    <jats:p>\n                      <jats:bold>Trial registration:<\/jats:bold>\n                      ClinicalTrials.gov NCT07185438.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0355676","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T17:48:13Z","timestamp":1786038493000},"page":"e0355676","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Feasibility, safety, and preliminary clinical efficacy of resting-state functional connectivity MRI-guided rTMS for adolescents with major depressive disorder: Protocol for a randomized, double-blind, three-arm, sham-controlled pilot 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