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Intracranial electroencephalography (EEG), performed presurgically in patients with drug-resistant and difficult-to-localize focal epilepsy, samples only a small fraction of brain tissue and thus requires strong hypotheses regarding the possible localization of the epileptogenic zone. EEG/fMRI (functional magnetic resonance imaging), a noninvasive tool resulting in hemodynamic responses, could contribute to the generation of these hypotheses. This study assessed how these responses, despite their interictal origin, predict the seizure-onset zone (SOZ).

We retrospectively studied 37 consecutive patients who underwent stereo-EEG (SEEG) and EEG/fMRI that resulted in significant hemodynamic responses. Hemodynamic response maps were co-registered to postimplantation anatomic imaging, allowing inspection of these responses in relation to SEEG electrode’s location. The area containing the most significant t-value (primary cluster) explored with an electrode was assessed for concordance with SEEG-defined SOZ. Discriminant analysis was performed to distinguish the primary clusters having a high probability of localizing the SOZ.

Thirty-one patients had at least one study with primary cluster explored with an electrode, and 24 (77%) had at least one study with primary cluster concordant with the SOZ. Each patient could have multiple types of interictal discharge and therefore multiple studies. Among 59 studies from the 37 patients, 44 had a primary cluster explored with an electrode and 30 (68%) were concordant with the SOZ. Discriminant analysis showed that the SOZ is predictable with high confidence (>90%) if the primary cluster is highly significant and if the next significant cluster is much less significant or absent.

The most significant hemodynamic response to interictal discharges delineates the subset of the irritative zone that generates seizures in a high proportion of patients with difficult-to-localize focal epilepsy. EEG/fMRI generates responses that are valuable targets for electrode implantation and may reduce the need for implantation in patients in whom the most significant response satisfies the condition of our discriminant analysis.