Spatiotemporal Patterns Differentiate Hippocampal Sharp-Wave Ripples from Interictal Epileptiform Discharges in Mice and Humans

Abstract

Hippocampal sharp-wave ripples (SPW-Rs) are high-frequency oscillations critical for memory consolidation in mammals. Despite extensive characterization in rodents, their application as biomarkers to track and treat memory dysfunction in humans is limited by coarse spatial sampling, interference from interictal epileptiform discharges (IEDs), and lack of consensus on human SPW-R localization and morphology. We demonstrate that mouse and human hippocampal ripples share spatial, spectral and temporal features, which are clearly distinct from IEDs. In 1024-channel hippocampal recordings from APP/PS1 mice, SPW-Rs were distinguishable from IEDs by their narrow localization to the CA1 pyramidal layer, narrowband frequency peaks, and multiple ripple cycles on the unfiltered local field potential. In epilepsy patients, ripples showed similar narrowband frequency peaks and visible ripple cycles in CA1 and the subiculum but were absent in the dentate gyrus. Conversely, IEDs showed a broad spatial extent and wide-band frequency power. We introduce a semi-automated, human ripple detection toolbox ("ripmap") selecting optimal detection channels and separating event waveforms by low-dimensional embedding. Our approach improves ripple detection accuracy, providing a firm foundation for future human memory research.