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.

The authors thank the healthy participants and patients with epilepsy who participated in this study. This work used computational resources provided by the Advanced Cyberinfrastructure Coordination Ecosystem: Services and Support (ACCESS), supported by the National Science Foundation (MED050005). This work was supported by the NIH/National Institute of Neurological Disorders and Stroke (R01 NS112816-01; J.I.T.), the American Epilepsy Society Postdoctoral Research Fellowship (1277380; Q.Z.), National Science and Technology Innovation 2030 of China (2022ZD0211800; Z.Z.), and the National Natural Science Foundation of China (82371951 and 81871345; Z.Z.).

Farber Institute for Neuroscience, Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA Qirui Zhang, Sam S. Javidi, Ankeeta Ankeeta, Michael R. Tracy Biomedical Engineering Department, McGill University, Montreal, QC, Canada McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada Department of Diagnostic Radiology, Jinling Hospital, Medical School of Nanjing University, Nanjing, PR China Correspondence to Zhiqiang Zhang or Joseph I.

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