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Objective: Animal and human studies have shown that the seizure‐generating region is vastly dependent on distant neuronal hubs that can decrease duration and propagation of ongoing seizures. However, we still lack a comprehensive understanding of the impact of distant brain areas on specific interictal and ictal epileptic activities (e.g., isolated spikes, spike trains, seizures). Such knowledge is critically needed, because all kinds of epileptic activities are not equivalent in terms of clinical expression and impact on the progression of the disease. Methods: We used surface high‐density electroencephalography and multisite intracortical recordings, combined with pharmacological silencing of specific brain regions in the well‐known kainate mouse model of temporal lobe epilepsy. We tested the impact of selective regional silencing on the generation of epileptic activities within a continuum ranging from very transient to more sustained and long‐lasting discharges reminiscent of seizures. Results: Silencing the contralateral hippocampus completely suppresses sustained ictal activities in the focus, as efficiently as silencing the focus itself, but whereas focus silencing abolishes all focus activities, contralateral silencing fails to control transient spikes. In parallel, we observed that sustained focus epileptiform discharges in the focus are preceded by contralateral firing and more strongly phase‐locked to bihippocampal delta/theta oscillations than transient spiking activities, reinforcing the presumed dominant role of the contralateral hippocampus in promoting long‐lasting, but not transient, epileptic activities. Significance: Altogether, our work provides suggestive evidence that the contralateral hippocampus is necessary for the interictal to ictal state transition and proposes that crosstalk between contralateral neuronal activity and ipsilateral delta/theta oscillation could be a candidate mechanism underlying the progression from short‐ to long‐lasting epileptic activities. [ABSTRACT FROM AUTHOR]

Mouse Model of Focal Cortical Dysplasia Type II Generates a Wide Spectrum of High-Frequency Activities Chvojka J, Prochazkova N, Rehorova M, Kudlacek J, Kylarova S, Kralikova M, Buran P, Weissova R, Balastik M, Jefferys JGR, Novak O, Jiruska P. Neurobiol Dis. 2024;190:106383. Epub 2023 Dec 17. PMID: 38114051. doi: 10.1016/j.nbd.2023.106383 High-frequency oscillations (HFOs) represent an electrographic biomarker of endogenous epileptogenicity and seizure-generating tissue that proved clinically useful in presurgical planning and delineating the resection area. In the neocortex, the clinical observations on HFOs are not sufficiently supported by experimental studies stemming from a lack of realistic neocortical epilepsy models that could provide an explanation of the pathophysiological substrates of neocortical HFOs. In this study, we explored pathological epileptiform network phenomena, particularly HFOs, in a highly realistic murine model of neocortical epilepsy due to focal cortical dysplasia type II (FCDII). FCD was induced in mice by the expression of the human pathogenic mammalian target of rapamycin (mTOR) gene mutation during embryonic stages of brain development. Electrographic recordings from multiple cortical regions in freely moving animals with FCD and epilepsy demonstrated that the FCD lesion generates HFOs from all frequency ranges, ie, gamma, ripples, and fast ripples up to 800 Hz. Gamma ripples were recorded almost exclusively in FCD animals, while fast ripples occurred in controls as well, although at a lower rate. Gamma-ripple activity is particularly valuable for localizing the FCD lesion, surpassing the utility of fast ripples that were also observed in control animals, although at significantly lower rates. Propagating HFOs occurred outside the FCD, and the contralateral cortex also generated HFOs independently of the FCD, pointing to a wider FCD network dysfunction. Optogenetic activation of neurons carrying mTOR mutation and expressing Channelrhodopsin-2 evoked fast ripple oscillations that displayed spectral and morphological profiles analogous to spontaneous oscillations. This study brings experimental evidence that FCDII generates pathological HFOs across all frequency bands and provides information about the spatiotemporal properties of each HFO subtype in FCD. The study shows that mutated neurons represent a functionally interconnected and active component of the FCD network, as they can induce interictal epileptiform phenomena and HFOs. [ABSTRACT FROM AUTHOR]