Inroads into epilepsy through high-frequency oscillations: Achievements and benchmark areas for improvement
Christos Panagiotis Lisgaras1,2, Birgit Frauscher3, Jean Gotman4
1Department of Psychiatry, New York University Grossman School of Medicine, New York, New York, USA.
Epilepsia
|January 28, 2026
Summary
High-frequency oscillations (HFOs) are crucial in epilepsy research, offering insights into disease mechanisms and treatment. New research explores their role in Alzheimer's disease, expanding their potential clinical applications.
Area of Science:
- Neuroscience
- Epileptology
- Biomedical Engineering
Background:
- High-frequency oscillations (HFOs), ranging from 80 Hz to several kHz, have been studied for over 20 years in epilepsy.
- HFOs play significant roles in epileptogenesis, ictogenesis, and the functional organization of epileptic brain tissue.
Purpose of the Study:
- To provide a historical overview and synthesize current knowledge on HFOs in epilepsy, drawing from the Third International Workshop on HFOs.
- To discuss the evolution of HFO research from single-center studies to multicenter analyses and meta-analyses.
- To highlight recent advancements and future research directions for HFOs in epilepsy and other neurological conditions like Alzheimer's disease.
Main Methods:
- Review and synthesis of clinical and basic science content from the Third International Workshop on HFOs in Epilepsy.
- Analysis of historical trends in HFO research, including invasive electroencephalographic recordings and multicenter studies.
- Examination of recent advancements in recording and analytical tools for HFO detection and application.
Main Results:
- HFOs are not uniform "one event fits all" biomarkers; their association with interictal spikes, seizures, and signal features like entropy aids in identifying epileptogenic tissue.
- Advances in technology have broadened the potential applications of HFOs in both clinical and basic science settings.
- Scalp-recorded HFOs show promise in assessing disease propensity, severity, and therapy response in epilepsy.
- HFOs are also found in Alzheimer's disease models, suggesting potential cross-disease relevance.
Conclusions:
- HFO research is an evolving field with significant progress, particularly in understanding their role in epilepsy.
- The association of HFOs with other electrophysiological markers offers new avenues for diagnosing and understanding epilepsy.
- Future research should focus on key knowledge gaps, with five benchmark areas identified for advancement.
- The presence of HFOs in both epilepsy and Alzheimer's disease models warrants further investigation into their shared or distinct pathophysiological roles.
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