Cortico-cortical evoked potentials in response to varying stimulation intensity improves seizure localization

Objective: As single pulse electrical stimulation (SPES) is increasingly utilized to help localize the seizure onset zone (SOZ), it is important to understand how stimulation intensity can affect the ability to use cortico-cortical evoked potentials (CCEPs) to delineate epileptogenic regions. Methods: We studied 15 drug-resistant epilepsy patients undergoing intracranial EEG monitoring and SPES with titrations of stimulation intensity. The N1 amplitude and distribution of CCEPs elicited in the SOZ and non-seizure onset zone (nSOZ) were quantified at each intensity. The separability of the SOZ and nSOZ using N1 amplitudes was compared between models using responses to titrations, responses to one maximal intensity, or both. Results: At 2 mA and above, the increase in N1 amplitude with current intensity was greater for responses within the SOZ, and SOZ response distribution was maximized by 4–6 mA. Models incorporating titrations achieved better separability of SOZ and nSOZ compared to those using one maximal intensity. Conclusions: We demonstrated that differences in CCEP amplitude over a range of current intensities can improve discriminability of SOZ regions. Significance: This study provides insight into the underlying excitability of the SOZ and how differences in current-dependent amplitudes of CCEPs may be used to help localize epileptogenic sites.