The role of electroencephalography in epilepsy research-From seizures to interictal activity and comorbidities

Abstract

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.

Keywords: EEG; analysis; animal models; genetic epilepsies; high‐frequency oscillations; mechanisms; preclinical.

FIGURE 1

Spatiotemporal properties of experimental electroencephalography (EEG). EEG recorded at a high sampling frequency can explore cerebral activities and processes operating at millisecond or even sub‐millisecond time scales. Therefore, we can study fast processes such as high‐frequency oscillations, interictal discharges, seizure onset, fast propagation, and synchrony. EEG can explore “slow” phenomena operating at the scales of seconds, minutes, or hours—such as seizures, spreading depolarization, or DC shifts. On the contrary, long‐term EEG recording is valuable for studying processes such as circadian rhythms, epilepsy rhythms, epileptogenesis, disease progression, seizure remission, or response to the treatment. The ability of EEG to simultaneously record fast and slow processes is instrumental in studying the long‐term profile of fast activities such as interictal epileptiform activity or high‐frequency oscillations. EEG recording ranging from single to multiple electrodes can provide spatial information from single‐cell activity to nearly a whole brain recording from multiple brain structures. The contemporary state‐of‐the‐art techniques of EEG recording can provide an enormous amount of information about epileptic brain dynamics (a gray area).

FIGURE 2

Electroencephalographic (EEG) recording in animals can be combined with other research methods and technologies. EEG can be combined with a variety of in vivo structural and functional imaging techniques including a head‐fixed microscope. Apart from brain electrical activity, other physiological parameters such as electrocardiography or respiration activity can be recorded simultaneously with EEG. Technological advances significantly contribute to the improvement of EEG recording techniques including new electrode types and the introduction of novel materials. Modern rechargeable telemetric devices allow for multichannel recordings for nearly unlimited periods of time. EEG is effectively combined with other research tools, such as chemogenetics or optogenetics, to help dissect the network activity with unprecedented cellular specificity. (Created in BioRender.com. Jiruska 2LFUK, P. (2025) https://BioRender.com/q90n176)

FIGURE 3

Examples of electroencephalography (EEG) artifacts from animal activity. (A) Movement artifact. Based on a review of simultaneously recorded videos; the rat was quiet and then started moving around the cage. The pattern fits the often‐used criteria for calling an EEG pattern a seizure: At least 5 s of repetitive activity that is at least twice the amplitude of baseline EEG. (B) Head‐scratching artifact. A prevalent pattern that also fits the above seizure criteria and that shows a pattern of evolution over time. As mentioned above, artifact as the source of the EEG change was confirmed by simultaneous video recording. (C) Spontaneous seizure from a rat with limbic epilepsy. Top line is from the frontal cortex; bottom line is from the hippocampus. The high‐amplitude activity in the frontal cortex channel is artifact, mainly from wet dog shakes. The hippocampal channel shows the classic evolution of repetitive activity that changes in amplitude and gradually slows. Of note, the recordings also show that the amplitude of the artifact is often much greater than that of a seizure (5–10 mV or greater vs 2–4 mV in the spontaneous seizure). In addition, the true seizure is much longer in duration (artifacts typically last 10–20 s, and the true seizure 30 s or more).