A universal method for seizure onset zone localization in focal epilepsy using standard deviation of spike amplitude

Background: Precisely localizing the seizure onset zone (SOZ) is critical for focal epilepsy surgery. Existing methods mainly focus on high-frequency activities in stereo-electroencephalography, but often fail when seizures are not driven by high-frequency activities. Recognized as biomarkers of epileptic seizures, ictal spikes in SOZ induce epileptiform discharges in other brain regions. Based on this understanding, we aim to develop a universal algorithm to localize SOZ and investigate how ictal spikes within the SOZ induce seizures. Methods: We proposed a novel metric called standard deviation of spike amplitude (SDSA) and utilized channelaveraged SDSA to describe seizure processes and detect seizures. By integrating SDSA values in specific intervals, the score for each channel located within SOZ was calculated. Channels with high SOZ scores were clustered as SOZ. The localization accuracy was asserted using area under the receiver operating characteristic (ROC) curve. Further, we analyzed early ictal signals from SOZ channels and investigated factors influencing their duration to reveal the seizure inducing conditions. Results: We analyzed data from 15 patients with focal epilepsy. The channel-averaged SDSA successfully detected all 28 seizures without false alarms. Using SDSA integration, we achieved precise SOZ localization with an average area under ROC curve (AUC) of 0.96, significantly outperforming previous methods based on highfrequency activities. Further, we discovered that energy of ictal spikes in SOZ was concentrated at a specific frequency distributed in [6, 12 Hz]. Additionally, we found that the higher the energy per second in this frequency band, the faster ictal spikes could induce seizures. Conclusion: The SDSA metric offered precise SOZ localization with robustness and low computational cost, making it suitable for clinical practice. By studying the propagation patterns of ictal spikes between the SOZ and non-SOZ, we suggest that ictal spikes from SOZ need to accumulate energy at a specific central frequency to induce epileptic spikes in non-SOZ, which may have significant implications for understanding the seizure onset pattern.