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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2018,10,16]]},"abstract":"<jats:p>NMDA-receptor antibodies (NMDAR-Abs) cause an autoimmune encephalitis with a diverse range of EEG abnormalities. NMDAR-Abs are believed to disrupt receptor function, but how blocking this excitatory synaptic receptor can lead to paroxysmal EEG abnormalities\u2014or even seizures\u2014is poorly understood. Here we show that NMDAR-Abs change intrinsic cortical connections and neuronal population dynamics to alter the spectral composition of spontaneous EEG activity and predispose brain dynamics to paroxysmal abnormalities. Based on local field potential recordings in a mouse model, we first validate a dynamic causal model of NMDAR-Ab effects on cortical microcircuitry. Using this model, we then identify the key synaptic parameters that best explain EEG paroxysms in pediatric patients with NMDAR-Ab encephalitis. Finally, we use the mouse model to show that NMDAR-Ab\u2013related changes render microcircuitry critically susceptible to overt EEG paroxysms when these key parameters are changed, even though the same parameter fluctuations are tolerated in the in silico model of the control condition. These findings offer mechanistic insights into circuit-level dysfunction induced by NMDAR-Ab.<\/jats:p>","DOI":"10.1073\/pnas.1804846115","type":"journal-article","created":{"date-parts":[[2018,9,27]],"date-time":"2018-09-27T15:55:19Z","timestamp":1538063719000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":50,"title":["NMDA-receptor antibodies alter cortical microcircuit dynamics"],"prefix":"10.1073","volume":"115","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0316-5818","authenticated-orcid":false,"given":"Richard E.","family":"Rosch","sequence":"first","affiliation":[{"name":"Wellcome Trust Centre for Neuroimaging, Institute of Neurology, University College London, London WC1N 3AR, United Kingdom;"},{"name":"Developmental Neurosciences Programme, Great Ormond Street Institute of Child Health, University College London, London WC1N 3EH, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sukhvir","family":"Wright","sequence":"additional","affiliation":[{"name":"School of Life and Health Sciences, Aston University, Birmingham B4 7ET, United Kingdom;"},{"name":"Department of Paediatric Neurology, Birmingham Children\u2019s Hospital, Birmingham B4 6NH, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8321-7085","authenticated-orcid":false,"given":"Gerald","family":"Cooray","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for Neuroimaging, Institute of Neurology, University College London, London WC1N 3AR, United Kingdom;"},{"name":"Department of Clinical Neurophysiology, Karolinska Institute, 171 77 Solna, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita","family":"Papadopoulou","sequence":"additional","affiliation":[{"name":"ToNIC Toulouse Neuroimaging Center, INSERM\/Universit\u00e9 Toulouse III-Paul Sabatier (UPS), 31024 Toulouse, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sushma","family":"Goyal","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurophysiology, Evelina London Children\u2019s Hospital, Guy\u2019s and St. Thomas\u2019 NHS Foundation Trust, London SE1 7EH, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Lim","sequence":"additional","affiliation":[{"name":"Children\u2019s Neurosciences, Evelina London Children\u2019s Hospital, Guy\u2019s and St. Thomas\u2019 NHS Foundation Trust, London SE1 7EH, United Kingdom;"},{"name":"Faculty of Life Sciences and Medicine, Kings College London, London SE1 7EH, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Vincent","sequence":"additional","affiliation":[{"name":"Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6618-1199","authenticated-orcid":false,"given":"A. 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