Replay of Interictal Sequential Activity Shapes the Epileptic Network Dynamics

Both the imbalance of neuronal excitation and inhibition, and the network disorganization may lead to hyperactivity in epilepsy. However, the insufficiency of seizure data poses the challenge of elucidating the network mechanisms behind the frequent and recurrent abnormal discharges. Our study of two extensive intracranial EEG datasets revealed that the seizure onset zone exhibits recurrent synchronous activation of interictal events. These synchronized discharges formed repetitive sequential patterns, indicative of a stable and intricate network structure within the seizure onset zone (SOZ). We hypothesized that the frequent replay of interictal sequential activity shapes the structure of the epileptic network, which in turn supports the occurrence of these discharges. The Hopfield-Kuramoto oscillator network model was employed to characterize the formation and evolution of the epileptic network, encoding the interictal sequential patterns into the network structure using the Hebbian rule. This model successfully replicated patient-specific interictal sequential activity. Dynamic change of the network connections was further introduced to build an adaptive Kuramoto model to simulate the interictal to ictal transition. The Kuramoto oscillator network with adaptive connections (KONWAC) model we proposed essentially combines two scales of Hebbian plasticity, shaping both the stereotyped propagation and the ictal transition in epileptic networks through the interplay of regularity and uncertainty in interictal discharges. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by the National Key R&D Program of China(2017YFA0205904). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee/IRB of Yuquan Hospital of Tsinghua University gave ethical approval for this work. All participants, or their legal guardians, provided informed consent to participate in this study. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.