Hierarchical alterations of brain network coupling and its clinical and cognitive relevance in systemic lupus...

Brain network alterations are common in systemic lupus erythematosus (SLE), but the coupling between structural and functional networks remains unclear. To investigate hierarchical alterations in structural-functional coupling (SFC) and their relationships with cognition and serological markers, we enrolled 63 female patients with SLE and 68 healthy controls who underwent multimodal MRI and neuropsychological assessment. Structural and functional networks were parcellated using the Schaefer-200 atlas and organized into seven Yeo functional systems. Structural connections were classified as rich-club, feeder, or local, and SFC was quantified at the whole-brain, network, and hierarchical levels. Principal component analysis of laboratory immune measures summarized the dominant covariance patterns in the humoral and antiphospholipid-related marker sets. Compared with the controls, the SLE patients showed reduced whole-brain SFC and decreased coupling within the default mode and frontoparietal networks. A hierarchical analysis revealed reductions in both the rich-club and local SFCs. The antiphospholipid-related component correlated negatively with the DMN and local SFCs. Specific serological indices, including anti-RNP and IgG, were associated with network-level SFC alterations, and reduced DMN SFC was associated with lower MMSE scores. Support vector regression models showed significant predictive associations of altered SFC features with cognitive scores and selected laboratory indices. These findings indicate multilevel disruption of structure-function correspondence in SLE, particularly in higher-order networks and hierarchical backbone connections, and suggest that SFC may provide a useful framework for linking immune dysregulation to brain network dysfunction and cognitive impairment.