The superior longitudinal fasciculus and its functional triple-network mechanisms in brooding

Brooding, which refers to a repetitive focus on one's distress, is associated with functional connectivity within Default-Mode, Salience, and Executive-Control networks (DMN; SN; ECN), comprising the so-called “triple-network” of attention. Individual differences in brain structure that might perseverate dysfunctional connectivity of brain networks associated with brooding are less clear, however. Using diffusion and functional Magnetic Resonance Imaging, we explored multimodal relationships between brooding severity, white-matter microstructure, and resting-state functional connectivity in depressed adults (N = 32–44), and then examined whether findings directly replicated in a demographically-similar, independent sample (N = 36–45). Among the fully-replicated results, three core findings emerged. First, brooding severity is associated with functional integration and segregation of the triple-network, particularly with a Precuneal subnetwork of the DMN. Second, microstructural asymmetry of the Superior Longitudinal Fasciculus (SLF) provides a robust structural connectivity basis for brooding and may account for over 20% of its severity (Discovery: adj. R(2) = 0.18; Replication: adj. R(2) = 0.22; MSE = 0.06, Predictive R(2) = 0.22). Finally, microstructure of the right SLF and auxiliary white-matter is associated with the functional connectivity correlates of brooding, both within and between components of the triple-network (Discovery: adj. R(2) = 0.21; Replication: adj. R(2) = 0.18; MSE = 0.03, Predictive R(2) = 0.21–0.22). By cross-validating multimodal discovery with replication, the present findings help to reproducibly unify disparate perspectives of brooding etiology. Based on that synthesis, our study reformulates brooding as a microstructural-functional connectivity neurophenotype.