Pathological and Physiological Significance of Hippocampal Ripples in Epilepsy

Ripple activity is defined as a high-frequency synchronous neural activity that has emerged as an important biomarker of epilepsy, both in research and clinical practice. In intracranial electroencephalography, ripple-band activity is closely linked to epileptogenicity and has been investigated as a marker to guide localization of epileptogenic tissue and predict surgical outcomes. Simultaneously, in the hippocampus, ripple activity additionally includes physiological sharp-wave ripples (SWRs), which play essential roles in memory consolidation, retrieval, and the selection of experiences for long-term storage. This overlap gives hippocampal ripple activity dual clinical significance: it may indicate pathological synchrony related to epilepsy, and it can also indicate the physiological processes that support memory and other higher cognitive functions. This review summarizes the current knowledge regarding the dual significance of hippocampal ripple activity in epilepsy. First, the pathological relevance of high-frequency oscillations as biomarkers of epileptogenicity and the physiological role of SWRs in hippocampal-cortical information processing are outlined. Subsequently, the methodological challenges involved in distinguishing pathological ripples from physiological SWRs in human intracranial recordings are discussed. Recent advances in consensus-based criteria, spatiotemporal analyses, and machine learning-based detection methods are further reviewed. Mechanistic frameworks further indicate that ripples reflect a shared synchrony-generating substrate, whose meaning depends on the network state, behavioral context, and spatial relation to the epileptogenic focus. Finally, ripple activity could be interpreted not only as a local hippocampal event but also as a marker of hippocampo-neocortical network state, with potential implications for epileptogenicity assessment, surgical planning, and function-preserving treatment strategies. Understanding the dual role of the hippocampal ripple activity may provide a basis for more precise epilepsy therapies that balance seizure control and memory preservation.