Update on the mechanisms and roles of high‐frequency oscillations in seizures and epileptic disorders

Summary High‐frequency oscillations ( HFO s) are a type of brain activity that is recorded from brain regions capable of generating seizures. Because of the close association of HFO s with epileptogenic tissue and ictogenesis, understanding their cellular and network mechanisms could provide valuable information about the organization of epileptogenic networks and how seizures emerge from the abnormal activity of these networks. In this review, we summarize the most recent advances in the field of HFO s and provide a critical evaluation of new observations within the context of already established knowledge. Recent improvements in recording technology and the introduction of optogenetics into epilepsy research have intensified experimental work on HFO s. Using advanced computer models, new cellular substrates of epileptic HFO s were identified and the role of specific neuronal subtypes in HFO genesis was determined. Traditionally, the pathogenesis of HFO s was explored mainly in patients with temporal lobe epilepsy and in animal models mimicking this condition. HFO s have also been reported to occur in other epileptic disorders and models such as neocortical epilepsy, genetically determined epilepsies, and infantile spasms, which further support the significance of HFO s in the pathophysiology of epilepsy. It is increasingly recognized that HFO s are generated by multiple mechanisms at both the cellular and network levels. Future studies on HFO s combining novel high‐resolution in vivo imaging techniques and precise control of neuronal behavior using optogenetics or chemogenetics will provide evidence about the causal role of HFO s in seizures and epileptogenesis. Detailed understanding of the pathophysiology of HFO s will propel better HFO classification and increase their information yield for clinical and diagnostic purposes.