Spatiotemporal patterns differentiate hippocampal sharp-wave ripples from interictal epileptiform discharges in mice and humans

Hippocampal sharp-wave ripples (SPW-Rs) are high-frequency oscillations critical for memory consolidation. Despite extensive characterization in rodents, their detection in humans is limited by coarse spatial sampling, interictal epileptiform discharges (IEDs), and a lack of consensus on human ripple localization and morphology. Here, we demonstrate that mouse and human hippocampal ripples share spatial, spectral and temporal features, which are clearly distinct from IEDs. In recordings from male APP/PS1 mice, SPW-Rs were distinguishable from IEDs by multiple criteria. Hippocampal ripples recorded during NREM sleep in female and male surgical epilepsy patients exhibited similar narrowband frequency peaks and multiple ripple cycles in the CA1 and subiculum regions. Conversely, IEDs showed a broad spatial extent and wide-band frequency power. We developed a semi-automated, ripple curation toolbox (ripmap) to separate event waveforms by low-dimensional embedding to reduce false-positive rate in selected ripple channels. Our approach improves ripple detection and provides a firm foundation for future human memory research. Identifying hippocampal ripples in humans is challenged by epileptic activity and coarse sampling. By comparing high resolution recordings in rodents and limited sampling in humans, the authors identify key ripple features and introduce a pipeline for more accurate ripple detection.