Nocturnal synchronization between hippocampal ripples and cortical delta power is a biomarker of hippocampal epileptogenicity

Objective: Hippocampal ripples are biomarkers of epileptogenicity in patients with epilepsy, and physiological features characterize memory function in healthy individuals. Discriminating between pathological and physiological ripples is important for identifying the epileptogenic (EP) zone; however, distinguishing them from waveforms is difficult. This study hypothesized that the nocturnal synchronization of hippocampal ripples and cortical delta power classifies EP and physiological hippocampi. Methods: We enrolled 38 patients with electrodes implanted in the hippocampus or the parahippocampal gyrus between April 2014 and March 2023 at our institution. We classified 11 patients (11 hippocampi) into the EP group, who were pathologically diagnosed with hippocampal sclerosis, and five patients (six hippocampi) into the non-epileptogenic (NE) group, whose hippocampi had no epileptogenicity. Hippocampal ripples were detected using intracranial electroencephalography of the hippocampal or parahippocampal electrodes and presented as ripple rates per second. Cortical delta power (0.5-4 Hz) was assessed using cortical electrodes. The Pearson correlation coefficient between the ripple rates and the cortical delta power (CRD) was calculated for the intracranial electroencephalographic signals obtained every night during the recordings. Results: Hippocampal ripples detected from continuous recording for approximately 10 days demonstrated similar frequency characteristics between the EP and NE groups. However, CRDs in the EP group (mean [standard deviation]: 0.20 [0.049]) were significantly lower than those in the NE group (0.67 [0.070], F (1,124) = 29.6, p < 0.0001 (group), F (9,124) = 1.0, p = 0.43 (day); two-way analysis of variance). Based on the minimum CRDs during the 10-day recordings, the two groups were classified with 94.1% accuracy. Conclusion: CRD is a biomarker of hippocampal epileptogenicity.