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Temporal Dynamics of BOLD fMRI Predict Intracranially-Confirmed Seizure Onset Zones in Drug-Resistant Epilepsy

Nenning, K.-H.; Zengin, E.; Xu, T.; Freund, E.; Markowitz, N.; Johnson, S.; Bonelli, S. B.; Franco, A. R.; Colcombe, S. J.; Milham, M. P.; Mehta, A. D.; Bickel, S.

2026-04-20 neuroscience
10.64898/2026.04.15.718821 bioRxiv
Show abstract

ObjectiveIn individuals with drug-resistant epilepsy, accurately identifying the brain regions where seizures originate is a critical prerequisite to guide surgical treatment and achieve seizure freedom. To accomplish this, intracranial EEG is considered the gold standard, providing the spatiotemporal high-resolution data necessary to pinpoint epileptogenic activity. However, this precision is achieved through an invasive procedure with significant patient burden, which is fundamentally limited by the electrode placement and spatial coverage. MethodsIn this study, we investigated the potential utility of preoperative resting-state fMRI to non-invasively map alterations in brain dynamics at the whole brain level. Region-wise brain dynamics were quantified with complementary measures of local autocorrelation decay rates. We assessed the capacity of these derived features to effectively identify intracranial EEG confirmed seizure onset zones in 18 individuals with drug-resistant medial temporal lobe epilepsy. Overall, the study cohort contained 3867 implanted electrodes of which 159 classified as seizure onset zones by two independent board-certified epileptologists. ResultsOverall, our findings reveal more constrained temporal dynamics for brain regions associated with seizure onsets compared to non-seizure onset zones. Individual-level prediction showed a performance better than chance in 15 of the 18 patients. The overall predictive performance across all patients yielded a median AUC of 0.81, a median true positive rate of 0.75, and a median true negative rate of 0.83. Furthermore, in a subset of 13 patients, those with negative seizure outcomes showed higher probabilities of seizure onset zone predictions outside the resection area compared to those with good outcomes. SignificanceOverall, our findings suggest that altered temporal dynamics derived from preoperative resting-state fMRI represent a promising non-invasive approach for delineating epileptogenic tissue, potentially informing intervention strategies and guiding electrode placement.

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