Complementary axes of functional system integrity and integration with divergent clinical correlates characterize focal epilepsy

Focal epilepsy affects distributed brain systems, yet characterizations of patient-specific network organization that are clinically meaningful remain limited. Using resting-state functional MRI, we estimated overlapping individualized networks and derived two complementary axes (1) network correspondence, indexing system integrity through canonical system expression, and (2) k-hubness, indexing cross-system integration through multi-network participation. We studied a presurgical cohort of 305 patients with focal epilepsy and 224 healthy participants and an independent validation cohort of 903 patients spanning focal and common generalized and childhood epilepsy syndromes and 666 healthy participants. Correspondence disruption was broadly shared across focal epilepsies, whereas k-hubness alterations showed lateralized and syndrome-dependent redistributions of cross-system integration. The axes shared variance but showed modest preferential associations, with correspondence relating to cognition and k-hubness to epilepsy clinical features. Together, these measures characterize common and heterogeneous alterations in individualized brain system organization, linking complementary aspects of network topology to cognitive and clinical variation. Zhang and colleagues identify two complementary aspects of brain network topology in focal epilepsy, with system integrity showing modest preferential associations with cognition and system integration with clinical features.