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The aim of this study was to compare patients with<jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content>\u2010refractory and<jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content>\u2010responsive<jats:styled-content style=\"fixed-case\">IGE<\/jats:styled-content>in order to determine whether there are group differences in generalized spike and wave discharge (<jats:styled-content style=\"fixed-case\">GSWD<\/jats:styled-content>) generators that may be associated with<jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content>resistance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Of 89<jats:styled-content style=\"fixed-case\">IGE<\/jats:styled-content>patients who underwent electroencephalography (<jats:styled-content style=\"fixed-case\">EEG<\/jats:styled-content>) combined with functional magnetic resonance imaging (<jats:styled-content style=\"fixed-case\">fMRI<\/jats:styled-content>;<jats:styled-content style=\"fixed-case\">EEG<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">fMRI<\/jats:styled-content>), 25 with<jats:styled-content style=\"fixed-case\">GSWD<\/jats:styled-content>s identified in<jats:styled-content style=\"fixed-case\">EEG<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">fMRI<\/jats:styled-content>data were included. Simultaneous acquisition of 64 channels of<jats:styled-content style=\"fixed-case\">EEG<\/jats:styled-content>data at 10\u00a0kHz was performed using an<jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content>\u2010compatible<jats:styled-content style=\"fixed-case\">EEG<\/jats:styled-content>cap and amplifier at 4<jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>.<jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content>resistance was defined as lack of seizure control despite therapeutic dose of<jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Findings<\/jats:title><jats:p>The<jats:styled-content style=\"fixed-case\">fMRI<\/jats:styled-content>blood oxygen\u2013level dependent (<jats:styled-content style=\"fixed-case\">BOLD<\/jats:styled-content>) correlates of<jats:styled-content style=\"fixed-case\">GSWD<\/jats:styled-content>in the entire group involved midline thalamus, frontal regions comprising<jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>rodmann areas 6, 24, and 32, and temporal lobes diffusely. When<jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content>\u2010responsive and<jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content>\u2010resistant patients were compared,<jats:styled-content style=\"fixed-case\">BOLD<\/jats:styled-content>signal increases were noted in the<jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content>\u2010resistant patients in medial frontal cortex, along the paracingulate gyrus (Montreal Neurological Institute;<jats:styled-content style=\"fixed-case\">MNI<\/jats:styled-content>x\u00a0=\u00a02, y\u00a0=\u00a013.6, z\u00a0=\u00a045.9), and anterior insula bilaterally (right<jats:styled-content style=\"fixed-case\">MNI<\/jats:styled-content>x\u00a0=\u00a037.6, y\u00a0=\u00a07.8, z\u00a0=\u00a00.6, left<jats:styled-content style=\"fixed-case\">MNI<\/jats:styled-content>x\u00a0=\u00a0\u221235.3, y\u00a0=\u00a013.6, z\u00a0=\u00a0\u22125.3).<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Our findings support the hypothesis that<jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content>\u2010resistant and<jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content>\u2010responsive patients may have different<jats:styled-content style=\"fixed-case\">GSWD<\/jats:styled-content>generators. Furthermore, we hypothesize that these differences in<jats:styled-content style=\"fixed-case\">GSWD<\/jats:styled-content>generators may be the reason for different responses to<jats:styled-content style=\"fixed-case\">VPA<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.12062","type":"journal-article","created":{"date-parts":[[2013,1,7]],"date-time":"2013-01-07T14:17:14Z","timestamp":1357568234000},"page":"471-480","source":"Crossref","is-referenced-by-count":49,"title":["The relationship between the localization of the generalized spike and wave discharge generators and the response to valproate"],"prefix":"10.1111","volume":"54","author":[{"given":"Jerzy P.","family":"Szaflarski","sequence":"first","affiliation":[{"name":"Department of Neurology and the Cincinnati Epilepsy Center University of Cincinnati Cincinnati Ohio U.S.A"},{"name":"Pediatric Neuroimaging Research Consortium Cincinnati Children's Hospital Medical Center Cincinnati Ohio U.S.A"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Kay","sequence":"additional","affiliation":[{"name":"Neuroscience Graduate Program University of Cincinnati Cincinnati Ohio U.S.A"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean","family":"Gotman","sequence":"additional","affiliation":[{"name":"Montreal Neurological Institute Montreal Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael D.","family":"Privitera","sequence":"additional","affiliation":[{"name":"Department of Neurology and the Cincinnati Epilepsy Center University of Cincinnati Cincinnati Ohio U.S.A"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott K.","family":"Holland","sequence":"additional","affiliation":[{"name":"Pediatric Neuroimaging Research Consortium Cincinnati Children's Hospital Medical Center Cincinnati Ohio U.S.A"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,1,7]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh136"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1994.tb02433.x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.2000.0599"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1528-1157.2001.36400.x"},{"key":"e_1_2_7_6_1","unstructured":"AnderssonJ JenkinsonM SmithS. 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