[in Japanese]

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 1) Ictal DC shifts in chronic epilepsy:
 By using subdural electrodes, we demonstrated that ictal DC shifts with a time constant of 10 seconds preceded normal ictal patterns, and reported the as a new EEG biomarker for localizing the focus of epilepsy surgery, particularly in intractable neocortical epilepsy, regardless of the pathological tissue of the focus (Ikeda et al., 1996, 1999, 2020; Ikeda, 2008, 2018; Inoue et al., 2019; Kanazawa et al., 2025).
 2) Simultaneous recording of ictal DC shifts and ictal HFOs:
 As the clinical application of interictal HFOs has been investigated, both ictal DC shifts and ictal HFOs were well demonstrated to be recorded simultaneously. In chronic epilepsy, the former precedes the latter (active DC shifts) (Kanazawa et al., 2015). As a result, both are gradually recognized in clinical practice as reliable EEG biomarkers of epilepsy foci, as evidenced by multicenter collaborative studies (Nakatani et al., 2022). This has also been confirmed in animal experiments (Ikeda et al., 2020).
 3) Clinical usefulness of time constants from 10 seconds to 2 seconds:
 By comparing ictal DC shifts between display time constants of 10 seconds and 2 seconds by using data with a recording time constant of 10 seconds, the existence of 2 types of ictal DC shifts, i.e., rapid- and slow development DC shifts, were revealed by cluster analysis, and the correspondence with pathological findings was revealed, with the former type accounting for more than 60% (Kajikawa et al., 2022). In addition, wide-band EEG analysis of patients with intractable focal epilepsy with a recording time constant of 2 seconds demonstrated the clinical usefulness of ictal DC shifts (Izumi et al., 2023).
 4) Wider application of wide-band digital EEG to scalp EEG and to the wide-spectrum of neurological disorders:
 Clinical and social implementation of wide-band EEG in acute brain injury as critical care EEG, migraine, transient focal neurological episodes (TFNEs), a part of dementia disorders, etc. (Togo et al., 2018; Hosokawa et al., 2024; Ikeda et al., 2024; Hayashi et al., 2025). As the next step from the current stage where AI analysis of clinical EEG target the already established EEG signals, it is highly anticipated that new EEG signals, i.e., wide-band EEG data, will be implemented and next-generation EEG will be implemented in the global society.
 5) We are now in place to discuss the relationship with cortical spreading depolarization, one of the biggest mysteries in clinical EEG, based on a new EEG perspective including the function of the astrocytes.

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Epilepsy affects approximately 1% of the world’s population; however, 30% of patients remain resistant to antiepileptic drugs. Reactive astrogliosis is commonly observed in tissue samples from epileptic patients; this process involves astrocytic Ca²⁺ hyperactivity and contributes to neuronal hyperexcitability. However, the role of reactive astrocytes in the pathology of epilepsy is yet to be established. This review therefore focuses on the role of reactive astrocytes in epileptogenesis with an emphasis on Ca²⁺ signaling. The mechanisms underlying the induction of reactive astrocytes and their multifaceted roles in the pathophysiology of epilepsy are discussed. An improved understanding of these processes may lead to novel therapeutic strategies targeting astrocytes, which may benefit patients with drug-resistant epilepsy.

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Epilepsy is a neurological disorder characterized by recurrent seizures, often driven by complex interactions between neurons and glial cells. While neuronal mechanisms of epileptogenesis have been extensively studied, growing evidence highlights the critical role of astrocytes in modulating network excitability through tripartite synapses. Astrocytes regulate extracellular ion homeostasis, neurotransmitter clearance, and synaptic plasticity, and their dysfunction contributes to seizure generation and propagation. In this review, we focus on the involvement of astrocytes in intractable epilepsy, particularly in hippocampal sclerosis (HS) and cavernous angioma (CA). Using flavoprotein fluorescence imaging and histopathological analyses, we demonstrate that astrocytic dysfunction, including impaired potassium buffering and glutamate homeostasis, plays a crucial role in hyperexcitability and seizure dynamics. Furthermore, we discuss how aberrant neural circuits, such as the subiculum-CA1 pathway in HS and the perilesional astrocytosis regions in CA, are linked to astrocyte-mediated mechanisms of epileptogenesis. These findings emphasize the importance of astrocyte-neuron interactions in seizure development and suggest that targeting astrocyte-related mechanisms could provide novel therapeutic strategies for epilepsy treatment.

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