Leveraging DIRECT fMRI Large-scale Data for Precision TMS Targeting in Major Depressive Disorder

Brisbane Convention & Exhibition Centre 

The subgenual anterior cingulate cortex (sgACC) is central to the pathophysiology of major depressive disorder (MDD), with its functional connectivity (FC) to the left dorsolateral prefrontal cortex (DLPFC) influencing outcomes of transcranial magnetic stimulation (TMS). However, inconsistent findings in sgACC-FC research often result from small sample sizes and site-specific variations, underscoring the need for harmonised, large-scale analyses. Leveraging the Depression Imaging REsearch ConsorTium (DIRECT) Phase II—a globally harmonised fMRI dataset with 1660 MDD patients and 1341 healthy controls—we systematically delineated sgACC-FC abnormalities and their implications for personalised TMS targeting. Enhanced sgACC-DLPFC FC in MDD patients relative to healthy controls shifted the sgACC anti-correlation peak within the DLPFC, altering the optimal TMS target location. Using these insights, we developed an MDD big data-guided TMS targeting algorithm that integrates group-level FC maps with individual-level brain activity for precise, patient-specific TMS target identification. This symposium talk will highlight the advantages of harmonised fMRI datasets in overcoming site variability, enhancing statistical power, and driving clinical applications. We demonstrate how harmonised, cross-cohort analyses improve our understanding of MDD-related FC disruptions and provide a foundation for actionable biomarkers. Furthermore, our algorithm’s validation across independent clinical samples shows its potential to improve TMS outcomes through personalised targeting.