{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T16:50:30Z","timestamp":1785775830620,"version":"3.56.0"},"reference-count":58,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Cenobamate (CNB) is an effective antiseizure medication, though its mechanisms of efficacy remain incompletely understood. We assessed changes in cortical responses to transcranial magnetic stimulation (TMS) following CNB treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We recruited people with drug\u2010resistant focal epilepsy scheduled to start add\u2010on CNB in a tertiary epilepsy center. We performed TMS coupled with electromyography (EMG) and electroencephalography (EEG) at baseline, at 100\u2009mg\/day and at the maximum tolerated or minimum effective dose. Participants were categorized as responders (\u226550% seizure reduction) or nonresponders. We used linear mixed models and cluster\u2010based permutation tests to assess CNB effects on resting motor thresholds (rMTs), intracortical inhibition and the amplitude, mean field power and event\u2010related spectral perturbation of TMS\u2010evoked EEG potentials (TEPs). For TMS measures that were significantly affected by CNB dose (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05), we assessed differences between responders and non\u2010responders and correlations with seizure frequency.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Twenty\u2010eight participants completed the study (16 females; median age, 50\u2009years). rMT (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01) increased and cortical silent period (CSP) lengthened (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.03) with increasing CNB dose. These changes did not differ between responders and nonresponders, nor did they correlate with reduced seizure frequency. Short\u2010 and long\u2010interval intracortical inhibition, as well as all TEP parameters, remained unchanged.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>While CSP lengthening may merely reflect higher stimulation intensities, rMT increases align with CNB's suggested modulation of sodium channels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>rMT changes that are independent of clinical response suggest that sodium channel effects do not fully account for the therapeutic efficacy of CNB.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain Language Summary<\/jats:title>\n                    <jats:p>We used magnetic brain stimulation in people with epilepsy to find out how the antiseizure medication cenobamate affects brain activity. As its dose increased, cenobamate raised the stimulation strength required to activate a muscle, known as the resting motor threshold (rMT). These changes did not predict a reduction in seizures. This suggests that cenobamate's effectiveness involves more than its effects on mechanisms linked to the rMT.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi4.70255","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T10:41:12Z","timestamp":1778755272000},"page":"1171-1183","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Impact of cenobamate on cortical responses to transcranial magnetic stimulation in people with drug\u2010resistant focal\u00a0epilepsy"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0881-9315","authenticated-orcid":false,"given":"Silvano R.","family":"Gefferie","sequence":"first","affiliation":[{"name":"Stichting Epilepsie Instellingen Nederland (SEIN)  Heemstede Netherlands"},{"name":"Department of Neurology Leiden University Medical Centre  Leiden Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0147-107X","authenticated-orcid":false,"given":"Diego","family":"Jim\u00e9nez\u2010Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Epilepsy UCL Queen Square Institute of Neurology  London UK"},{"name":"Chalfont Centre for Epilepsy  Chalfont St Peter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6708-6396","authenticated-orcid":false,"given":"Gerhard H.","family":"Visser","sequence":"additional","affiliation":[{"name":"Stichting Epilepsie Instellingen Nederland (SEIN)  Heemstede Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0277-8484","authenticated-orcid":false,"given":"Robert M.","family":"Helling","sequence":"additional","affiliation":[{"name":"Stichting Epilepsie Instellingen Nederland (SEIN)  Heemstede Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arn M. 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