{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:43:08Z","timestamp":1791902588295,"version":"4.3.4"},"reference-count":41,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T00:00:00Z","timestamp":1644364800000},"content-version":"unspecified","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001839","name":"University Grants Committee","doi-asserted-by":"crossref","award":["15100120"],"award-info":[{"award-number":["15100120"]}],"id":[{"id":"10.13039\/501100001839","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Repetitive transcranial magnetic stimulation (rTMS) with theta burst stimulation (i.e. TBS) of the dorsolateral prefrontal cortex (DLPFC) is an innovative treatment for major depressive disorder (MDD). However, fewer than 50% of patients show sufficient response to this treatment; markers for response prediction are urgently needed. Research shows considerable individual variability in the brain responses to rTMS. However, whether differences in individual DLPFC modulation by rTMS can be used as a predictive marker for treatment response remains to be investigated. Here, we present a research programme that will exploit the combination of functional near-infrared spectroscopy (fNIRS) with brain stimulation. Concurrent TBS\/fNIRS will allow us to systematically investigate TBS-induced modulation of blood oxygenation as a proxy for induced brain activity changes. The findings from this study will (1) elucidate the immediate effects of excitatory and inhibitory TBS on prefrontal activity in TBS treatment-na\u00efve patients with MDD and (2) validate the potential utility of TBS-induced brain modulation at baseline for the prediction of antidepressant response to 4\u2009weeks of daily TBS treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and analysis<\/jats:title><jats:p>Open-label, parallel-group experiment consisting of two parts. In part 1, 70 patients and 37 healthy controls will be subjected to concurrent TBS\/fNIRS. Intermittent TBS (iTBS) and continuous TBS (cTBS) will be applied on the left and right DLPFC, respectively. fNIRS data will be acquired before, during and several minutes after stimulation. In part 2, patients who participated in part 1 will receive a 4\u2009week iTBS treatment of the left DLPFC, performed daily for 5\u2009days per week. Psychometric evaluation will be performed periodically and at 1\u2009month treatment follow-up. Statistical analysis will include a conventional, as well as a machine learning approach.<\/jats:p><\/jats:sec><jats:sec><jats:title>Ethics and dissemination<\/jats:title><jats:p>Ethics approval was obtained from the Institutional Review Board. Findings will be disseminated through scientific journals, conferences and university courses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial registration number<\/jats:title><jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT04526002\">NCT04526002<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1136\/bmjopen-2021-053896","type":"journal-article","created":{"date-parts":[[2022,2,10]],"date-time":"2022-02-10T17:15:14Z","timestamp":1644513314000},"page":"e053896","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Protocol for a prospective open-label clinical trial to investigate the utility of concurrent TBS\/fNIRS for antidepressant treatment optimisation"],"prefix":"10.1136","volume":"12","clinical-trial-number":[{"clinical-trial-number":"nct04526002","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01192685","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Rebecca L D","family":"Kan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1627-6434","authenticated-orcid":false,"given":"Arthur D P","family":"Mak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherry K W","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2580-3371","authenticated-orcid":false,"given":"Bella B B","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth N 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