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This study compared the earliest recorded <jats:styled-content style=\"fixed-case\">EEG<\/jats:styled-content> from infants prior to <jats:styled-content style=\"fixed-case\">ES<\/jats:styled-content> onset (n\u00a0=\u00a016) and from infants who did not develop <jats:styled-content style=\"fixed-case\">ES<\/jats:styled-content> (n\u00a0=\u00a028). Five minutes of stage <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> or quiet sleep was clipped and filtered into canonical <jats:styled-content style=\"fixed-case\">EEG<\/jats:styled-content> frequency bands. Mutual information values between each pair of <jats:styled-content style=\"fixed-case\">EEG<\/jats:styled-content> channels were compared directly and used as a weighted graph to calculate graph measures of global efficiency, characteristic path length, average clustering coefficient, and modularity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>At the group level, infants who later developed <jats:styled-content style=\"fixed-case\">ES<\/jats:styled-content> had increased <jats:styled-content style=\"fixed-case\">EEG<\/jats:styled-content> connectivity in sleep. They had higher mutual information values between most <jats:styled-content style=\"fixed-case\">EEG<\/jats:styled-content> channels in all frequency bands adjusted for age. Infants who later developed <jats:styled-content style=\"fixed-case\">ES<\/jats:styled-content> had higher global efficiency and average clustering coefficients, shorter characteristic path lengths, and lower modularity across most frequency bands adjusted for age. This suggests that infants who went on to develop <jats:styled-content style=\"fixed-case\">ES<\/jats:styled-content> had increased local and long\u2010range <jats:styled-content style=\"fixed-case\">EEG<\/jats:styled-content> connectivity with less segregation of graph regions into distinct modules.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>This study suggests that increased neural connectivity precedes clinical <jats:styled-content style=\"fixed-case\">ES<\/jats:styled-content> onset in a cohort of infants with <jats:styled-content style=\"fixed-case\">TSC<\/jats:styled-content>. Overconnectivity may reflect progressive pathologic network synchronization culminating in generalized <jats:styled-content style=\"fixed-case\">ES<\/jats:styled-content>. Further research is needed before scalp <jats:styled-content style=\"fixed-case\">EEG<\/jats:styled-content> connectivity measures can be used as a potential biomarker of <jats:styled-content style=\"fixed-case\">ES<\/jats:styled-content> risk and treatment response in pre\u2010symptomatic infants with <jats:styled-content style=\"fixed-case\">TSC<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.16284","type":"journal-article","created":{"date-parts":[[2019,7,12]],"date-time":"2019-07-12T07:44:50Z","timestamp":1562917490000},"page":"1721-1732","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Increased electroencephalography connectivity precedes epileptic spasm onset in infants with tuberous sclerosis complex"],"prefix":"10.1111","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5796-6015","authenticated-orcid":false,"given":"Peter E.","family":"Davis","sequence":"first","affiliation":[{"name":"Department of Neurology Boston Children's Hospital Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kush","family":"Kapur","sequence":"additional","affiliation":[{"name":"Department of Neurology Boston Children's Hospital Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajna","family":"Filip\u2010Dhima","sequence":"additional","affiliation":[{"name":"Department of Neurology Boston Children's Hospital Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara K.","family":"Trowbridge","sequence":"additional","affiliation":[{"name":"Department of Neurology Boston Children's Hospital Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaina","family":"Little","sequence":"additional","affiliation":[{"name":"Department of Neurology Boston Children's Hospital Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Wilson","sequence":"additional","affiliation":[{"name":"Neuromodulation Division Department of Psychiatry and Biobehavioral Sciences Semel Institute for Neuroscience and Human Behavior David Geffen School of Medicine at University of California Los Angeles Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Leuchter","sequence":"additional","affiliation":[{"name":"Neuromodulation Division Department of Psychiatry and Biobehavioral Sciences Semel Institute for Neuroscience and Human Behavior David Geffen School of Medicine at University of California Los Angeles Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth M.","family":"Bebin","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Alabama at Birmingham Birmingham Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darcy","family":"Krueger","sequence":"additional","affiliation":[{"name":"Department of Neurology and Rehabilitation Medicine Cincinnati Children's Hospital Medical Center Cincinnati Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hope","family":"Northrup","sequence":"additional","affiliation":[{"name":"Department of Pediatrics McGovern Medical School The University of Texas Health Science Center at Houston Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce Y.","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurology UCLA Mattel Children's Hospital David Geffen School of Medicine University of California at Los Angeles Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa","family":"Sahin","sequence":"additional","affiliation":[{"name":"Department of Neurology Boston Children's Hospital Harvard Medical School Boston Massachusetts"},{"name":"F.M. 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