Electroencephalography (EEG) has been instrumental in epilepsy research for the past century, both for basic and translational studies. Its contributions have advanced our understanding of epilepsy, shedding light on the pathophysiology and functional organization of epileptic networks, and the mechanisms underlying seizures. Here we re-examine the historical significance, ongoing relevance, and future trajectories of EEG in epilepsy research. We describe traditional approaches to record brain electrical activity and discuss novel cutting-edge, large-scale techniques using micro-electrode arrays. Contemporary EEG studies explore brain potentials beyond the traditional Berger frequencies to uncover underexplored mechanisms operating at ultra-slow and high frequencies, which have proven valuable in understanding the principles of ictogenesis, epileptogenesis, and endogenous epileptogenicity. Integrating EEG with modern techniques such as optogenetics, chemogenetics, and imaging provides a more comprehensive understanding of epilepsy. EEG has become an integral element in a powerful suite of tools for capturing epileptic network dynamics across various temporal and spatial scales, ranging from rapid pathological synchronization to the long-term processes of epileptogenesis or seizure cycles. Advancements in EEG recording techniques parallel the application of sophisticated mathematical analyses and algorithms, significantly augmenting the information yield of EEG recordings. Beyond seizures and interictal activity, EEG has been instrumental in elucidating the mechanisms underlying epilepsy-related cognitive deficits and other comorbidities. Although EEG remains a cornerstone in epilepsy research, persistent challenges such as limited spatial resolution, artifacts, and the difficulty of long-term recording highlight the ongoing need for refinement. Despite these challenges, EEG continues to be a fundamental research tool, playing a central role in unraveling disease mechanisms and drug discovery.

Alberta Children's Hospital Research Institute Hotchkiss Brain Institute Alberta Health Services and University of Calgary Calgary Canada

Center for Dementia Research The Nathan S Kline Institute for Psychiatric Research New York State Office of Mental Health Orangeburg New York USA

CNRS UMR7275 Institute of Molecular and Cellular Pharmacology Valbonne Sophia Antipolis France

Department of Clinical and Experimental Epilepsy UCL Queen Square Institute of Neurology London UK

Department of Epileptology University Hospital Bonn Bonn Germany

Department of Neurology School of Medicine New York University New York New York USA

Department of Neuroscience and Medical Genetics Meyer Children's Hospital IRCSS Florence Italy

Department of Physiology 2nd Faculty of Medicine Charles University Prague Czech Republic

Department of Physiology and Medical Physics Royal College of Surgeons in Ireland Dublin Ireland

Department of Psychiatry New York University Grossman School of Medicine New York New York USA

Discipline of Physiology School of Medicine Trinity College Dublin Dublin Ireland

Dominick P Purpura Department of Neuroscience Albert Einstein College of Medicine Bronx New York USA

Epilepsy Unit Fondazione IRCCS Istituto Neurologico Carlo Besta Milan Italy

FutureNeuro Research Ireland Centre Royal College of Surgeons in Ireland Dublin Ireland

Inserm U1323 Valbonne Sophia Antipolis France

Instituto Cajal CSIC Madrid Spain

Langone Medical Center New York University New York New York USA

Neuroscience Institute Langone Medical Center New York University New York New York USA

Saul R Korey Department of Neurology Isabelle Rapin Division of Child Neurology Albert Einstein College of Medicine Bronx New York USA

School of Pharmacy and Biomolecular Sciences Royal College of Surgeons in Ireland Dublin Ireland

Université Côte d'Azur Valbonne Sophia Antipolis France

University of Florence Florence Italy

University of Virginia Charlottesville Virginia USA

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