Clinical and Neurophysiological Effects of Robotically Delivered fMRI-Guided Personalized Transcranial Magnetic Stimulation Therapy for Depression

Introduction: Repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) is an established treatment for refractory major depressive disorder (MDD), but treatment outcomes vary substantially from person to person. Recent evidence suggests that incorporating neuroimaging-based targeting may help improve clinical outcomes. Here, we report the initial clinical outcomes of our open-label fMRI-personalized treatment protocol from the Queensland Neurostimulation Centre. Methods: This open-label, nonrandomized study was conducted between November 2021 and September 2024. Participants were a referred sample aged between 19 and 84, meeting the criteria for treatment-resistant MDD (N = 61). They received 20- or 30-weekday sessions of DLPFC rTMS. The stimulation site was personalized using each individual's fMRI brain connectivity data. Results: The primary outcome was change in the Montgomery-& Aring;sberg Depression Rating Scale (MADRS). MADRS was lower post-treatment (d = 1.78, p < 0.001), with 52% and 33% response and remission rates observed. Likewise, anxiety scores (Hamilton Anxiety Rating Scale) were lower post-treatment (d = 1.27, p < 0.001), with 46% and 28% response and remission rates observed. The treatment was most effective in patients who qualified for randomized controlled trials (RCTs; N = 19, MADRS response = 74%, remission = 53%) and least effective in patients with bipolar or neurological disorders (N = 8, MADRS response = 38%, remission = 25%). Neurophysiologically, functional brain connectivity in the personalized DLPFC-subgenual cingulate cortex pathway was less anticorrelated post-treatment (d = 0.63, p < 0.001). Conclusion: Our findings provide new clinical and neurophysiological evidence supporting the high effectiveness of fMRI connectivity-guided personalized rTMS for MDD, especially in individuals without complex comorbidities. The results encourage future RCTs to assess the superiority of personalized targeting over standard TMS.