Functional brain networks including Default Mode, Salience, and Executive Control (DMN; SN; ECN), collectively called the 'triple-network', are associated with Depressive Rumination (DR) severity in Major Depressive Disorder (MDD). The underlying white-matter (WM) microstructure supporting these networks and its precise role in DR remains unknown, however. Using diffusion MRI and resting-state BOLD fMRI, we explored multimodal relationships between DR, WM microstructure, and triple-network functional connectivity in adults with MDD (N = 39), and then replicated our analyses in an independent dataset of adults with MDD (N = 39). Results showed that higher DR severity was negatively associated with: (a) microstructure of primary and secondary WM fibers spanning the right Superior Longitudinal Fasciculus and surrounding clusters, (b) functional network connectivity of the Cingulo-Opercular SN (coSN), Precuneal DMN (pDMN), and frontal ECN (fECN), (c) inverse correlations between the pDMN and each of the coSN and fECN, and (d) a direct correlation between the fECN and coSN. Ultimately, thirty-one findings replicated fully or partially, lending support to the conclusion that individual differences in WM microstructure, resting-state functional connectivity of the triple-network, and their multivariate, microstructural-functional intersection, provide a neurobiological basis for depressive rumination.

A Reproducible Neurobiology of Depressive Rumination