Intrinsic and extrinsic connectivity of the seizure onset zone at rest and during stimulation

About half of patients who undergo epilepsy surgery for drug-resistant epilepsy have seizure recurrence, supporting the need for approaches that more accurately identify the epileptogenic zone, defined as the brain areas whose removal causes cessation of seizures. Altered network connectivity has emerged as a candidate biomarker of the epileptogenic zone, but how connectivity is altered in the epileptogenic zone remains uncertain, with prior studies reporting inconsistent results.

We hypothesized that a difference in intrinsic versus extrinsic connectivity of the epileptogenic zone may explain prior discrepant findings.

We retrospectively studied a multicenter cohort of 37 adult and 42 pediatric patients who underwent intracranial EEG recording and brain stimulation as part of epilepsy surgery planning. We measured spontaneous connectivity using Pearson correlation and perturbational connectivity using stimulation evoked potentials, modeling the connectivity according to the location of contacts in relation to the seizure onset zone while controlling for inter-electrode distance.

For both adult and pediatric patients, resting connectivity was higher within compared to outside the seizure onset zone. However, resting connectivity between channels within and outside seizure onset zone was reduced. Stimulation connectivity followed a similar pattern, with elevated connectivity within the seizure onset zone but reduced connectivity from within to outside seizure onset zone.

These results support the hypothesis that the seizure onset zone is disconnected from the rest of the brain but intrinsically hyperconnected. This result helps reconcile prior inconsistencies across studies, aligns with basic science studies, and suggests an approach for future translational work aiming to localize the epileptogenic zone.