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However, only a small fraction of IEDs recorded by intracranial EEG (iEEG) are detectable on the scalp; the vast majority remain invisible on scalp recordings. Nevertheless, epilepsy is associated with important brain network alterations and cognitive symptoms between seizures. Our study aims to investigate the impact of these scalp\u2010negative IEDs on the whole\u2010brain network, particularly those produced in medial temporal regions, given their consistent involvement across patients, their potential implications in cognitive deficit, and their relevance in both epilepsy and Alzheimer disease. To achieve this, we leveraged simultaneous iEEG and high\u2010density EEG (hdEEG) recordings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed IEDs occurring solely in the medial temporal regions, not visible on the scalp, in nine patients with drug\u2010resistant epilepsy during simultaneous iEEG\u2010hdEEG recordings. These scalp\u2010negative IEDs were compared to epochs without any epileptic activity recorded in either modality. Spectral and network characteristics were investigated at the region of interest (ROI) for both modalities in different canonical frequency bands.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      ROI time courses reconstructed with hdEEG during IEDs exhibited sharp wave characteristics (cluster\u2010based corrected time\u2013frequency analysis), confirming that some information time\u2010locked to iEEG IEDs reached the scalp. Our findings revealed a significant frequency\u2010dependent, large\u2010scale increase in power and network features during scalp\u2010negative IEDs compared to epochs without IEDs, at the whole\u2010brain level and within specific ROIs, including the ipsilateral hippocampus (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.05, false discovery rate corrected).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>Despite being localized in medial temporal regions, these IEDs have a widespread impact on functional brain networks, potentially contributing to cognitive impairment in epilepsy. This study lays the groundwork for examining their real\u2010time effects on cognition, including in neurodegenerative conditions such as Alzheimer disease, where these IEDs can be present and difficult to detect.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi.70061","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T11:55:24Z","timestamp":1766404524000},"page":"1992-2006","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Scalp\u2010negative medial temporal interictal epileptic discharges alter large\u2010scale brain networks: A simultaneous high\u2010density\n                    <scp>electroencephalographic<\/scp>\n                    and intracranial\n                    <scp>electroencephalographic<\/scp>\n                    study"],"prefix":"10.1002","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6948-1055","authenticated-orcid":false,"given":"Nicolas","family":"Roehri","sequence":"first","affiliation":[{"name":"EEG and Epilepsy Unit, University Hospitals and Faculty of Medicine University of Geneva  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7979-0994","authenticated-orcid":false,"given":"Pia","family":"De Stefano","sequence":"additional","affiliation":[{"name":"EEG and Epilepsy Unit, University Hospitals and Faculty of Medicine University of Geneva  Geneva Switzerland"},{"name":"Neuro\u2010Intensive Care Unit, Department of Intensive Care University Hospitals of Geneva  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7682-2041","authenticated-orcid":false,"given":"Laurent","family":"Spinelli","sequence":"additional","affiliation":[{"name":"EEG and Epilepsy Unit, University Hospitals and Faculty of Medicine University of Geneva  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1145-242X","authenticated-orcid":false,"given":"Renaud","family":"Marquis","sequence":"additional","affiliation":[{"name":"EEG and Epilepsy Unit, University Hospitals and Faculty of Medicine University of Geneva  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2916-1302","authenticated-orcid":false,"given":"Stanislas","family":"Lagarde","sequence":"additional","affiliation":[{"name":"EEG and Epilepsy Unit, University Hospitals and Faculty of Medicine University of Geneva  Geneva Switzerland"},{"name":"Institut de Neurosciences Des Syst\u00e8mes, Aix\u2010Marseille Universit\u00e9, INSERM, INS  Marseille 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