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Updated: Mar 8, 2026
MRI-guided dmPFC-rTMS as a Treatment for Treatment-resistant Major Depressive Disorder
Published on: August 11, 2015
fMRI-guided V1-targeted rTMS improves depressive symptoms in adolescents and young adults with bipolar disorder: a
Xudong Zhao1,2, Hetong Zhou1, Xiaomei Zhang1,2
1Department of Psychiatry, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Background:
Bipolar depression (BD-D) in adolescents and young adults is associated with disrupted neural circuits underlying affective regulation, particularly those involving the orbitofrontal cortex (OFC). Despite the promise of repetitive transcranial magnetic stimulation (rTMS) as a non-invasive intervention, effective targeting strategies that engage these dysfunctional circuits remain insufficiently explored. This study investigates the clinical efficacy of a novel rTMS protocol targeting the primary visual cortex (V1) node of the V1-OFC functional circuit in adolescents and young adults with BD-D.
Methods:
We conducted a double-blind randomized controlled trial. Fifty-two adolescents and young adults BD-D participants were randomized to active rTMS group (10 Hz, 100% RMT) or sham rTMS group (20% RMT) targeting the V1 region that exhibited the strongest functional connectivity with the OFC (MNI: - 12, - 81, 6). rTMS was administered over 3 weeks (5 sessions/week, 15 sessions in total), with all participants receiving adjunctive lurasidone (40-80 mg/day). The primary outcome was the change in depressive symptoms measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) at baseline, week 3, and week 8. Secondary outcomes included HAMD-24, QIDS-SR, and HAMA. Resting-state fMRI was performed at baseline and after the 3-week intervention to examine changes in functional connectivity related to rTMS.
Results:
A total of 43 participants completed a 3-week intervention, and 37 completed the 8-week follow-up. Compared with the sham group, the active rTMS group showed significantly greater reductions in depressive symptoms. Between-group differences were significant on the primary outcome MADRS at week 8 (t(35) = - 3.595, pFDR < 0.01), with a parallel effect detected for the secondary outcome on the QIDS-SR (t(35) = - 3.653, pFDR < 0.01). HAMD-24 scores also differed significantly at week 3 (t(35) = - 3.921, pFDR < 0.01). No significant changes were found in anxiety symptoms. Resting-state fMRI indicated altered connectivity in the anterior cingulate cortex and right superior occipital gyrus, suggesting modulation of mood-related visual circuits. No severe adverse effects were reported in all participants.
Conclusions:
The study preliminarily demonstrated that the navigated rTMS precisely targeting the V1-OFC circuit may be a safe and potentially effective intervention for adolescents and young adults with BD-D.
Trial Registration:
ClinicalTrials.gov identifier: NCT05929183.
