Epileptogenicity alters intrahippocampal ripple propagation

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.

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.

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.

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.

Intrahippocampal propagation of ripples on oscillations (RonO, 80-250 Hz) is highest in the less-irritative hippocampus along the epileptogenicity spectrum despite their rates were similar.The proportions of hippocampal-to-mesial-temporal and hippocampal-to-neocortical RonO propagation remain constant across varying degrees of hippocampal epileptogenicity.Propagation proportions for fast RonO (fRonO, 250-600 Hz) do not differ significantly across the hippocampal epileptogenicity spectrum despite that their rates differ.

The hippocampus is a part of the brain that is crucial for memory. Sometimes, injured parts of the hippocampus create fast electrical brainwaves, called high-frequency oscillations (HFOs), which are linked to seizures. However, healthy parts of the hippocampus also create HFOs, and these are important for learning and memory. In this study, we wanted to know: do the brainwaves from an injured hippocampus spread differently through the brain than the brainwaves from a healthy one?