{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T08:42:46Z","timestamp":1792226566959,"version":"4.4.0"},"reference-count":45,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T00:00:00Z","timestamp":1784332800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T00:00:00Z","timestamp":1784332800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["583034287"],"award-info":[{"award-number":["583034287"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Despite decades of research, the circuit mechanisms that underlie focal epileptogenesis remain incompletely understood. In this study, we aimed to characterize the changes in hippocampal network activity induced by an epileptogenic insult.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In rats, prolonged electrical perforant pathway stimulation leads in a high percentage of animals to the development of temporal lobe epilepsy. However, a subset of animals remained apparently non\u2010epileptic for unknown reasons. We monitored alterations of neuronal activity by chronically recording the local field potential (LFP) from the hippocampal dentate gyrus before, during, and after the potentially epileptogenic insult and quantifying the time\u2010dependent changes in the periodic and the aperiodic components of the LFP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>It is intriguing that animals with epilepsy identified by subsequent spontaneous epileptic seizures were characterized by a transient increase in the aperiodic exponent, suggesting a shift toward a reduced local excitation\u2010to\u2010inhibition (E\/I) ratio during the first days after the perforant path stimulation. Furthermore, these animals developed a strong impairment of theta oscillation prevalence and regularity during early epileptogenesis. In contrast, resilient non\u2010epilepsy animals without spontaneous seizures showed neither this modulation in E\/I ratio nor a corruption of hippocampal theta activity. In fact, the increase in the aperiodic exponent on the first day after completion of the electrical stimulation paradigm could predict epileptogenesis with very high fidelity (area under the curve [AUC] 0.92) and correlated significantly with later seizure rate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>The very early phase of epileptogenesis seems to be dominated by a relative dominance of inhibitory synaptic activity in affected circuits. This finding opens the opportunity to dissect mechanisms of epileptogenesis and to test the effectiveness of anti\u2010epileptogenesis treatment in very early disease stages by allowing identification of individuals at high risk. Furthermore, it might offer a potential explanation for the frequently observed failure of anti\u2010epileptogenesis drugs boosting \u03b3\u2010aminobutyric acid (GABA)ergic inhibition.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi.70386","type":"journal-article","created":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T17:37:42Z","timestamp":1784396262000},"page":"5501-5513","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hippocampal network activity changes during early epileptogenesis predict subsequent epilepsy"],"prefix":"10.1002","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3478-0848","authenticated-orcid":false,"given":"Michael","family":"Str\u00fcber","sequence":"first","affiliation":[{"name":"Epilepsy Center Frankfurt Rhine\u2010Main, Department of Neurology, University Hospital Frankfurt Goethe University Frankfurt  Frankfurt am Main Germany"},{"name":"LOEWE Center for Personalized Translational Epilepsy Research (CePTER) Goethe University Frankfurt  Frankfurt am Main Germany"},{"name":"Cooperative Brain Imaging Center (CoBIC) University Hospital Frankfurt  Frankfurt am Main Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3853-0608","authenticated-orcid":false,"given":"Tristan Manfred","family":"St\u00f6ber","sequence":"additional","affiliation":[{"name":"Epilepsy Center Frankfurt Rhine\u2010Main, Department of Neurology, University Hospital Frankfurt Goethe University Frankfurt  Frankfurt am Main Germany"},{"name":"Cooperative Brain Imaging Center (CoBIC) University Hospital Frankfurt  Frankfurt am Main Germany"},{"name":"Institute of Computer Science and Campus Institute Data Science University G\u00f6ttingen  G\u00f6ttingen Germany"},{"name":"Circulant Labs  Bensheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Sch\u00fctz","sequence":"additional","affiliation":[{"name":"Epilepsy Center Frankfurt Rhine\u2010Main, Department of Neurology, University Hospital Frankfurt Goethe University Frankfurt  Frankfurt am Main Germany"},{"name":"LOEWE Center for Personalized Translational Epilepsy Research (CePTER) Goethe University Frankfurt  Frankfurt am Main Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara","family":"Costard","sequence":"additional","affiliation":[{"name":"Department of Neurology Philipps University  Marburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8014-3631","authenticated-orcid":false,"given":"Valentin","family":"Neubert","sequence":"additional","affiliation":[{"name":"Oscar Langendorff Institute of Physiology University of Rostock  Rostock Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Bauer","sequence":"additional","affiliation":[{"name":"Epilepsy Center Frankfurt Rhine\u2010Main, Department of Neurology, University Hospital Frankfurt Goethe University Frankfurt  Frankfurt am Main Germany"},{"name":"LOEWE Center for Personalized Translational Epilepsy Research (CePTER) Goethe University Frankfurt  Frankfurt am Main Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6225-3166","authenticated-orcid":false,"given":"Parsa","family":"Gharavi","sequence":"additional","affiliation":[{"name":"Epilepsy Center Frankfurt Rhine\u2010Main, Department of Neurology, University Hospital Frankfurt Goethe University Frankfurt  Frankfurt am Main Germany"},{"name":"Cooperative Brain Imaging Center (CoBIC) University Hospital Frankfurt  Frankfurt am Main Germany"},{"name":"AISA Solutions Inc.  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