Backgroud: Human brain function is attributable to highly organizednetwork of connections linking distinct brian areas.Recent studies have demonstrated that a small core of highly connected hub regions may play a central role in global information integration,together forming a densely interconnected rich club[1].Given that generalizedtonic-clonic seizure(GTCS)has been conceptualized as a network disorder[2],we hypothesized that the rich club connectivity disturbances may be related tothe pathophysiological abnormalities of GTCS.Methods: A group of 50 patients with GTCS(32 male and 18 female; mean age,25.90 years±7.75)and 60sex-and age-matched HC(33 male and 27 female; mean age,25.02 years ±6.22)wereincluded in this study.First,the whole brain was divided into 116 distinct and non-overlapping regions by masking the Automated Anatomical Labeling(AAL)map [3] to obtain the nodes of structural and functionalconnectivity networks.To construct the structural connectivity network in each subject,brain regions from MNI space were warped to the native diffusion space [4].Second,Diffusion tensor images(DTI)were realigned and corrected for motion and eddy current distortions.Whole-brain fiber tracking was performed in native diffusion space for each subject via Fiber Assignment by Continuous Tracking(FACT)algorithm as implemented in the Diffusion Toolkit [5].Third,DTI and resting-state functional magnetic resonance imaging signal correlations wereused to generate functional and structural connectivity connectomes.Rich club organization was examined derived from both structural and functional networks using graph theoretical analysis.We further measured the level of global efficiency and clustering in sub-networks: inside and outside the richcluborganization.Permutation testing was used to evaluate the statistical significance of observed effects Results: Patients exhibited significantly reduced rich club connectivity strength predominantlycomprising bilateral cortical and subcortical regions(p < 0.01 range k = 23 to k = 25;10000permutations,Figure 1).Meanwhile,for both the structural and functional connectomes,statistical testing revealed a reduced level of GE and C of networks inside the richcluborganizationin patients Furthermore,in patients,lower levels of rich club connectivity was foundto be correlated with longer duration of illness(all p< 0.05,Figure2).Conclusions:Our study identified disrupted rich club organization of structural andfunctional connectomes in GTCS,suggestinga reduced level of connectivity among central hubs of the brain.Additionally,our analyses further indicate that the impaired structural interconnectivity of richclub network in patients with GTCS may contribute to a reduced levels of functional communication capacity and an added effect of illness on a preexisting vulnerability.Our findings emphasize a central role for abnormal rich club organization in the pathophysiological mechanism underlying GTCS.