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Despite their clinical relevance, their mechanisms of generation remain poorly understood. It is assumed that brain activity switches abruptly, unpredictably, and supposedly randomly to these epileptic transients. We aim to study the period preceding these epileptic discharges, to extract potential proepileptogenic mechanisms supporting their expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used multisite intracortical recordings from patients who underwent intracranial monitoring for refractory epilepsy, the majority of whom had a mesial temporal lobe seizure onset zone. Our objective was to evaluate the existence of proepileptogenic windows before interictal epileptic discharges. We tested whether the amplitude and phase synchronization of slow oscillations (.5\u20134\u00a0Hz and 4\u20137\u00a0Hz) increase before epileptic discharges and whether the latter are phase\u2010locked to slow oscillations. Then, we tested whether the phase\u2010locking of neuronal activity (assessed by high\u2010gamma activity, 60\u2013160\u00a0Hz) to slow oscillations increases before epileptic discharges to provide a potential mechanism linking slow oscillations to interictal activities.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Changes in widespread slow oscillations anticipate upcoming epileptic discharges. The network extends beyond the irritative zone, but the increase in amplitude and phase synchronization is rather specific to the irritative zone. In contrast, epileptic discharges are phase\u2010locked to widespread slow oscillations and the degree of phase\u2010locking tends to be higher outside the irritative zone. Then, within the irritative zone only, we observe an increased coupling between slow oscillations and neuronal discharges before epileptic discharges.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Our results show that epileptic discharges occur during vulnerable time windows set up by a specific phase of slow oscillations. The specificity of these permissive windows is further reinforced by the increased coupling of neuronal activity to slow oscillations. These findings contribute to our understanding of epilepsy as a distributed oscillopathy and open avenues for future neuromodulation strategies aiming at disrupting proepileptic mechanisms.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.17020","type":"journal-article","created":{"date-parts":[[2021,8,2]],"date-time":"2021-08-02T13:56:07Z","timestamp":1627912567000},"page":"2357-2371","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Slow oscillations open susceptible time windows for epileptic discharges"],"prefix":"10.1111","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4824-6408","authenticated-orcid":false,"given":"Laurent","family":"Sheybani","sequence":"first","affiliation":[{"name":"EEG and Epilepsy Unit \/ Neurology Department of Clinical Neuroscience University Hospitals and Faculty of Medicine of University of Geneva Geneva 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