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It has been proposed that there are truly epileptogenic and less pathological or even protective IEDs. Recent studies suggest that highly pathological IEDs are characterized by high-frequency oscillations (HFOs). Here, we aimed to dissect these \u2018HFO-IEDs\u2019 at the single-neuron level, hypothesizing that the underlying mechanisms are distinct from \u2018non-HFO-IEDs\u2019. Analysing hybrid depth electrode recordings from patients with temporal lobe epilepsy, we found that single-unit firing rates were higher in HFO- than in non-HFO-IEDs. HFO-IEDs were characterized by a pronounced pre-peak increase in firing, which coincided with the preferential occurrence of HFOs, whereas in non-HFO-IEDs, there was only a mild pre-peak increase followed by a post-peak suppression. Comparing each unit\u2019s firing during HFO-IEDs to its baseline activity, we found many neurons with a significant increase during the HFO component or ascending part, but almost none with a decrease. No such imbalance was observed during non-HFO-IEDs. Finally, comparing each unit\u2019s firing directly between HFO- and non-HFO-IEDs, we found that most cells had higher rates during HFO-IEDs and, moreover, identified a distinct subset of neurons with a significant preference for this IED subtype. In summary, our study reveals that HFO- and non-HFO-IEDs have different single-unit correlates. In HFO-IEDs, many neurons are moderately activated, and some participate selectively, suggesting that both types of increased firing contribute to highly pathological IEDs.<\/jats:p>","DOI":"10.1093\/brain\/awab288","type":"journal-article","created":{"date-parts":[[2021,7,30]],"date-time":"2021-07-30T15:17:50Z","timestamp":1627658270000},"page":"3078-3088","source":"Crossref","is-referenced-by-count":57,"title":["Interictal spikes with and without high-frequency oscillation have different single-neuron correlates"],"prefix":"10.1093","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7041-8806","authenticated-orcid":false,"given":"Tim A","family":"Guth","sequence":"first","affiliation":[{"name":"Epilepsy Center, Medical Center, University of Freiburg , Freiburg, Germany"},{"name":"Department of Neuropediatrics and Muscle Disorders, Medical Center, University of Freiburg , Freiburg, Germany"},{"name":"Faculty of Medicine, University of Freiburg , Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Kunz","sequence":"additional","affiliation":[{"name":"Epilepsy Center, Medical Center, University of Freiburg , Freiburg, Germany"},{"name":"Faculty of Medicine, University of Freiburg , Freiburg, Germany"},{"name":"Department of Biomedical Engineering, Columbia University , New York, NY, USA"},{"name":"Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg , Freiburg, Germany"},{"name":"Faculty of Biology, University of Freiburg , Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armin","family":"Brandt","sequence":"additional","affiliation":[{"name":"Epilepsy Center, Medical Center, University of Freiburg , Freiburg, Germany"},{"name":"Faculty of Medicine, University of Freiburg , Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"D\u00fcmpelmann","sequence":"additional","affiliation":[{"name":"Epilepsy Center, Medical Center, University of Freiburg , Freiburg, Germany"},{"name":"Faculty of Medicine, University of Freiburg , Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1601-5384","authenticated-orcid":false,"given":"Kerstin A","family":"Klotz","sequence":"additional","affiliation":[{"name":"Epilepsy Center, Medical Center, University of Freiburg , Freiburg, Germany"},{"name":"Department of Neuropediatrics and Muscle Disorders, Medical Center, University of Freiburg , Freiburg, Germany"},{"name":"Faculty of Medicine, University of Freiburg , Freiburg, Germany"},{"name":"Berta-Ottenstein-Programme, Faculty of Medicine, University of Freiburg , Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter C","family":"Reinacher","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Freiburg , Freiburg, Germany"},{"name":"Stereotactic and Functional Neurosurgery, Medical Center\u2014University of Freiburg , Freiburg, Germany"},{"name":"Fraunhofer Institute for Laser Technology , Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Schulze-Bonhage","sequence":"additional","affiliation":[{"name":"Epilepsy Center, Medical Center, University of Freiburg , Freiburg, Germany"},{"name":"Faculty of Medicine, University of Freiburg , Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Jacobs","sequence":"additional","affiliation":[{"name":"Department of Neuropediatrics and Muscle Disorders, Medical Center, University of Freiburg , Freiburg, Germany"},{"name":"Faculty of Medicine, University of Freiburg , Freiburg, Germany"},{"name":"Department of Paediatrics and Department of Neuroscience, Cumming School of Medicine, University of Calgary , Calgary, Alberta, Canada"},{"name":"Hotchkiss Brain Institute and Alberta Children\u2019s Hospital Research Institute, University of Calgary , Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Sch\u00f6nberger","sequence":"additional","affiliation":[{"name":"Epilepsy Center, Medical Center, University of Freiburg , Freiburg, Germany"},{"name":"Department of Neuropediatrics and Muscle Disorders, Medical Center, University of Freiburg , Freiburg, Germany"},{"name":"Faculty of Medicine, University of Freiburg , Freiburg, Germany"},{"name":"Berta-Ottenstein-Programme, Faculty of Medicine, University of Freiburg , Freiburg, 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