Epileptogenicity alters intrahippocampal ripple propagation

Objective: Tracing the propagation of high-frequency oscillations (HFOs) aids in localizing epileptogenic regions and improving surgical outcomes. We examined how hippocampal epileptogenicity influences the propagation properties of the HFOs it generates. Methods: We analyzed non-REM sleep stereo-EEG from 49 patients (68 hemispheres) with verified hippocampal contacts. Hippocampi were stratified by excitability: 28 seizure onset zone (SOZ), 22 more-irritative non-SOZ (>6 interictal epileptiform discharges [IED]/min), and 18 less-irritative non-SOZ (<6 IED/min). To isolate significant HFO propagation pathways, we constructed empirical temporal networks (maximum latency 150 ms) and validated them against 1,000 permutation-generated surrogates. We then compared the proportion of statistically significant propagating HFOs originating from hippocampal contacts across these groups. Results: We examined ripples on oscillation (RonO, 80-250 Hz) and fast ripples on oscillation (FRonO, 250-600 Hz). FRonO, but not RonO, rates were significantly elevated in hippocampal SOZ versus non-SOZ contacts (p<1e-9). Intrahippocampal RonO propagation proportion was highest in less-irritative non-SOZ compared to more-irritative non-SOZ (p<0.05) and SOZ (p<0.001). Across groups, we found no other differences in RonO or FRonO propagation proportions, including spread to other mesial-temporal structures or the neocortex. Significance: Intrahippocampal RonO propagation is proportionally greater in less-irritative non-SOZ tissue than in the epileptogenic hippocampus. Distinguishing physiological from pathological RonO using signal features alone remains challenging. Our work suggests these categories are not distinct; rather, RonO signals and their underlying hippocampal substrates likely exist on a continuous physiological-to-pathological spectrum. Furthermore, RonO propagation may serve as a novel metric to quantify hippocampal epileptogenicity.