Objective: Postoperative resting-state functional magnetic resonance imaging (MRI) in children with intractable epilepsy has not been quantified in relation to seizure outcome. Therefore, its value as a biomarker for epileptogenic pathology is not well understood. Methods: In a sample of children with intractable epilepsy who underwent prospective resting-state seizure onset zone (SOZ)-targeted epilepsy surgery, postoperative resting-state functional MRI (rs-fMRI) was performed 6 to 12 months later. Graded normalization of the postoperative resting-state SOZ was compared to seizure outcomes, patient, surgery, and anatomical MRI characteristics. Results: A total of 64 cases were evaluated. Network-targeted surgery, followed by postoperative rs-fMRI normalization was significantly (p < 0.001) correlated with seizure reduction, with a Spearman rank correlation coefficient of 0.83. Of 39 cases with postoperative rs-fMRI SOZ normalization, 38 (97%) became completely seizure free. In contrast, of the 25 cases without complete rs-fMRI SOZ normalization, only 3 (5%) became seizure free. The accuracy of rs-fMRI as a biomarker predicting seizure freedom is 94%, with 96% sensitivity and 93% specificity. Interpretation: Among seizure localization techniques in pediatric epilepsy, network-targeted surgery, followed by postoperative rs-fMRI normalization, has high correlation with seizure freedom. This study shows that rs-fMRI SOZ can be used as a biomarker of the epileptogenic zone, and postoperative rs-fMRI normalization is a biomarker for SOZ quiescence.

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