Negative BOLD response to interictal discharges in epilepsy using intracranial EEG-fMRI.

Introduction: Combined electroencephalography and functional magnetic resonance imaging (EEG-fMRI) identifies regions of neural activity in response to interictal epileptiform discharges (IEDs). While positive BOLD responses have historically been used to localize epileptogenic tissue, negative BOLD responses remain poorly understood. This study examined the spatial relationship between positive and negative BOLD responses to IEDs and their associations with epileptogenic tissue and the default mode network (DMN) using intracranial EEG-fMRI. Methods: 70 adult participants (57 met inclusion criteria), with drug-resistant focal epilepsy, underwent intracranial EEG-fMRI during presurgical monitoring. BOLD response maps were generated and maximum positive and negative clusters identified. Linear mixed models examined distances between BOLD clusters and both IED-generating contacts and contacts closest to clinically-defined seizure onset zone. A subset of 38 participants were assessed for spatial overlap and functional connectivity with the DMN. Results: Maximum positive BOLD clusters were significantly closer to both IED-generating contacts (estimate = -30.0, 95% CI [-55.5, -4.37]) and seizure onset zone contacts (estimate = -32.7, 95% CI [-57.5, -8.43]) compared to maximum negative clusters, when the absolute maximum is positive. Negative BOLD clusters demonstrated significantly greater spatial overlap with the DMN than positive clusters (22.5% vs 10.0%, p = 0.04). Conclusions: Positive BOLD responses provide superior localization of epileptogenic tissue compared to negative responses in intracranial EEG-fMRI. In contrast, negative BOLD clusters show greater spatial overlap with the DMN, suggesting they may reflect network deactivation at the time of IED events. These findings support prioritizing positive BOLD responses for clinical decision-making in presurgical epilepsy evaluation.