Transfer Function Models for the Localization of Seizure Onset Zone From Cortico-Cortical Evoked Potentials

Surgical resection of the seizure onset zone (SOZ) could potentially lead to seizure-freedom in medically refractory epilepsy patients. However, localizing the SOZ can be a time consuming and tedious process involving visual inspection of intracranial electroencephalographic (iEEG) recordings captured during passive patient monitoring. Cortical stimulation is currently performed on patients undergoing invasive EEG monitoring for the main purpose of mapping functional brain networks such as language and motor networks. We hypothesized that evoked responses from single pulse electrical stimulation (SPES) can also be used to localize the SOZ as they may express the natural frequencies and connectivity of the iEEG network. To test our hypothesis, we constructed patient specific transfer function models from the evoked responses recorded from 22 epilepsy patients that underwent SPES evaluation and iEEG monitoring. We then computed the frequency and connectivity dependent “peak gain” of the system as measured by the ${\mathcal{H}}_{\infty }$ norm from systems theory. We found that in cases for which clinicians had high confidence in localizing the SOZ, the highest peak gain transfer functions with the smallest “floor gain” (gain at which the dipped ${\mathcal{H}}_{\infty }$ 3dB below DC gain) corresponded to when the clinically annotated SOZ and early spread regions were stimulated. In more complex cases, there was a large spread of the peak-to-floor (PF) ratios when the clinically annotated SOZ was stimulated. Interestingly for patients who had successful surgeries, our ratio of gains, agreed with clinical localization, no matter the complexity of the case. For patients with failed surgeries, the PF ratio did not match clinical annotations. Our findings suggest that transfer function gains and their corresponding frequency responses computed from SPES evoked responses may improve SOZ localization and thus surgical outcomes.