The DIRECT Consortium and REST-meta-MDD Project: Towards Neuroimaging Guided Precision Treatment of Major Depressive
Tue, May 14
|Virtual event
This 1-hour presentation will cover: (1) The establishment of the Depression Imaging REsearch ConsorTium (DIRECT) .(2) Outcomes from DIRECT Phase II, highlighting the roles of the sgACC and left DLPFC, vital for TMS outcomes. (3) Plans for multi-site clinical trials in DIRECT Phase III.
Time & Location
May 14, 2024, 6:00 p.m. – 7:00 p.m. PDT
Virtual event
About the event
Moderator: Dr Ruiyang Ge, University of British Columbia
Speaker: Dr Chao-Gan Yan, Professor at the Institute of Psychology, Chinese Academy of Sciences
Despite a growing neuroimaging literature on the pathophysiology of major depressive disorder (MDD), reproducible findings are lacking, likely reflecting mostly small sample sizes and heterogeneity in analytic approaches. To address these issues, the Depression Imaging REsearch ConsorTium (DIRECT) was launched.
DIRECT Phase I pooled 2428 functional brain images processed with a standardized pipeline across all participating sites for the REST-meta-MDD project.
DIRECT Phase II used a state-of-the-art, surface-based preprocessing pipeline to improve sensitivity. This time we focused on the subgenual anterior cingulate cortex (sgACC), which plays a central role in the pathophysiology of major depressive disorder (MDD), and its functional interactive profile with the left dorsal lateral prefrontal cortex (DLPFC) is associated with transcranial magnetic stimulation (TMS) treatment outcomes.
Leveraging the Phase II large multi-site sample (1660 MDD patients vs. 1341 healthy controls), we systematically delineated case-control difference maps of sgACC-FC. Then, in a sample of 25 individuals with treatment-resistant depression who had received repetitive TMS (rTMS) treatment, we examined the relationship between case-control differences in FCs between sgACC and their specific TMS targets and treatment outcomes. Next, we tested whether the position of the group mean FC-based target (previously determined in healthy participants) differed in MDD patients. Finally, we developed a dual regression (DR) based approach to integrate group-level statistical maps with individual-level spontaneous brain activity to evaluate individualized TMS target localization in MDD. We tested this approach in a sample of 16 individuals who had received rTMS. We found enhanced sgACC-DLPFC FC in MDD patients. The magnitude of case-control differences in FC between sgACC and TMS targets was related to clinical improvement. We found different peak sgACC anticorrelation locations in mean FC maps of MDD patients and HCs. More effective TMS targets were closer to individualized DR-based loci than to group-level targets.
As the proposed individualized approach for TMS targeting has the potential to improve TMS treatment outcome, we are going to launch multi-site prospective clinical trials collaborations for DIRECT Phase III. Through these endeavors, we hope to accelerate the translation of functional neuroimaging findings to clinical utility while building an open repository for the scientific community.