Superior longitudinal fasciculus microstructure and its functional triple-network mechanisms in depressive rumination

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Pisner, Derek Alexander

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Depressive rumination, which involves a repetitive focus on one's distress, is associated with function connectivity disturbances of Default-Mode, Salience, and Executive-Control networks, comprising the so-called "triple-network" of attention. Missing, however, is a multimodal account of rumination that neuroanatomically explains the perseveration of these dysfunctional networks as a stable human trait. Using diffusion and functional Magnetic Resonance Imaging, we explored multimodal relationships between rumination severity, white-matter microstructure, and resting-state functional connectivity in N=39 depressed adults, and then directly replicated our findings in a demographically-matched, independent sample (N=39). Among the fully-replicated results, three core findings emerged. First, rumination severity is associated with both disintegrated and desegregated functional connectivity of the triple-network. Second, global microstructural inefficiency of the right Superior Longitudinal Fasciculus (SLF) provides a neuroanatomical connectivity basis for rumination and accounts for anywhere between 25-37% of the variance in rumination (Discovery: p corr<0.01; Replication: p corr<0.01; MSE=0.05). Finally, microstructure of the right SLF and auxiliary white-matter is strongly associated with functional connectivity biomarkers of rumination, both within and between components of the triple-network (Discovery: R²=0.36, p corr<0.05; Replication: R²=0.25, p corr<0.05; MSE=0.04-0.06). By cross-validating discovery with replication, our findings advance a reproducible microstructural-functional brain connectivity model of depressive rumination that unifies neurodevelopmental and neurocognitive perspectives.



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