Intracranial EEG can identify epilepsy-related networks in patients with focal epilepsy; however, the association between network organization and post-surgical seizure outcomes remains unclear. Hubness serves as a critical metric to assess network organization by identifying brain regions that are highly influential to other regions. In this study, we tested the hypothesis that favorable post-operative seizure outcomes are associated with the surgical removal of interictal network hubs, measured by the novel metric "Resection-Hub Alignment Degree (RHAD)." We analyzed Phase II interictal intracranial EEG from 69 patients with epilepsy who were seizure-free (n = 45) and non-seizure-free (n = 24) 1 year post-operatively. Connectivity matrices were constructed from intracranial EEG recordings using imaginary coherence in various frequency bands, and centrality metrics were applied to identify network hubs. The RHAD metric quantified the congruence between hubs and resected/ablated areas. We used a logistic regression model, incorporating other clinical factors, and evaluated the association of this alignment regarding post-surgical seizure outcomes. There was a significant difference in RHAD in fast gamma (80-200 Hz) interictal network between patients with favorable and unfavorable surgical outcomes (p = .025). This finding remained similar across network definitions (i.e., channel-based or region-based network) and centrality measurements (Eigenvector, Closeness, and PageRank). The alignment between surgically removed areas and other commonly used clinical quantitative measures (seizure-onset zone, irritative zone, high-frequency oscillations zone) did not reveal significant differences in post-operative outcomes. This finding suggests that the hubness measurement may offer better predictive performance and finer-grained network analysis. In addition, the RHAD metric showed explanatory validity both alone (area under the curve [AUC] = .66) and in combination with surgical therapy type (resection vs ablation, AUC = .71). Our findings underscore the role of network hub surgical removal, measured through the RHAD metric of interictal intracranial EEG high gamma networks, in enhancing our understanding of seizure outcomes in epilepsy surgery.
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