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Objective:  This study aimed to explore the characteristics of phase-amplitude coupling in patients with frontal epilepsy based on their electrocorticography data, in order to identify the localization of epileptic regions and further guide clinical resection surgery.   Methods:  We adopted the modulation index based on the Kullback-Leibler distance, phase-amplitude coupling co-modulogram, and time-varying phase-amplitude modulogram to explore the temporal-spatial patterns and characterization of PAC strength during the period from inter- seizure to post-seizure. Taking the resected area as the gold standard, the epileptogenic zone was located based on MI values of 7 different seizure periods, and the accuracy of localization was measured by the area under the receiver operating curve.   Results:  (1) The PAC in the inter- and pre-seizure periods was weak and paroxysmal, but strong PAC channels were confined more to the seizure-onset zone and resection region. PAC during the seizure period was intense and persistent, but gradually deviated from the seizure-onset zone. (2) The characteristics of coupling strength of the inter- and pre-seizure EEG can be used to accurately locate the epileptogenic zone, which is better than that in periods after the beginning of a seizure. (3) In an epileptic seizure, the preferred phases of coupling were usually in the rising branches at the pre- and early-seizure stages, while those in the middle- and terminal-seizure were usually in the falling branch. We thus speculate that the coupling occurred in the rising branch can promote the recruitment of abnormal discharge, while the coupling occurred in the falling branch can inhibit the abnormal discharge.   Conclusion:  The findings suggest that the phase-amplitude coupling during inter- and pre-seizure is a promising marker of epileptic focus location. The preferred phase of coupling changed regularly with the time of epileptic seizure, suggesting that the surge and suppression of abnormal discharges are related to different phases.

Phase–Amplitude Coupling and Epileptogenic Zone Localization of Frontal Epilepsy Based on Intracranial EEG