Unveiling the Structural-Functional Interplay of Brain Networks in Depression: An Integrated DTI-fMRI Study

Diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) are powerful neuroimaging techniques providing complementary information on brain structural (SC) and functional (FC) connectivity, respectively. Integrating them gives a deeper understanding of brain structural-functional interplay, which is particularly relevant in the search for brain markers of psychiatric illnesses like major depressive disorder (MDD). In this study, a novel DTI-driven fMRI approach was developed and preliminarily tested to identify any alterations in structural-functional network coupling in MDD. FC was estimated from DTI-derived features within a normative healthy control (HC) framework, using linear and quadratic models. SC strength, shortest path length, and physical distance showed significant influences on FC prediction in the linear model, whereas path length was non-significant in the quadratic version. The models were applied to a pilot test set of MDD and HC, comparing the predictive performance of the models between the two groups. The results showed reduced whole-brain similarity between estimated and measured FC in MDD vs. HC. These findings were confirmed on a smaller scale, showing significant differences in the model reconstruction error of ROI-to-ROI connectivity in key resting-state networks. These results suggest that altered brain structural-functional interactions may underlie MDD, providing new insights into potential biomarkers.