Associations Between Left DLPFC iTBS-induced Functional Connectivity Changes and Depressive Symptoms: An Exploratory Study

Background: As a more efficient variant of repetitive transcranial magnetic stimulation (rTMS), intermittent theta-burst stimulation (iTBS) has been shown to effectively treat major depressive disorder (MDD). Resting-state functional connectivity (FC) is believed to help explain how iTBS exerts its therapeutic effects. Research findings regarding FC changes induced by iTBS targeting the left dorsolateral prefrontal cortex (DLPFC) are inconsistent, warranting exploratory investigations. In this study, we analyzed the effects of a 10-day iTBS treatment on changes in resting-state FC in patients with MDD. Methods: This study enrolled 29 patients with MDD from Tianjin Anding Hospital between February 2023 and November 2024. These patients received 10 days of left DLPFC iTBS treatment, with its efficacy closely monitored. A FC matrix was constructed using the Human Brainnetome Atlas as a template. Changes in FC were analyzed, and correlation analysis was conducted between baseline FC in different brain regions and depressive symptoms. Regression analysis was then performed to predict depressive symptoms improvement based on baseline FC. Results: Our results demonstrate that iTBS treatment yields a significant therapeutic effect, with response and remission rates of 62.07% and 31.03%, respectively. FC analysis revealed a reduction in positive FC between the ventromedial putamen (vmPu), precentral gyrus (PrG), and postcentral gyrus (PoG). The correlation between baseline FC of vmPu and PrG (r = 0.529, p = 0.003), as well as between vmPu and PoG (r = 0.545, p = 0.002), was found to be positively associated with improvements in depressive symptoms. Additionally, linear regression analysis indicated that these baseline FC predicted the extent of therapeutic improvement. Conclusion: Intervention with iTBS has demonstrated promising therapeutic effects in the treatment of depression. This study identified FC that correlates with treatment response and could predict improvement in depressive core symptoms. Trial Registration: Chinese Clinical Trial Registry (ChiCTR2100054793).