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Ion channels in EEG: isolating channel dysfunction in NMDA receptor antibody encephalitis

Symmonds, M; Moran, CH; Leite, MI; Buckley, C; Irani, SR; Stephan, KE; Friston, KJ; (2018) Ion channels in EEG: isolating channel dysfunction in NMDA receptor antibody encephalitis. Brain , 141 (6) pp. 1691-1702. 10.1093/brain/awy107. Green open access

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Abstract

Neurological and psychiatric practice frequently lack diagnostic probes that can assess mechanisms of neuronal communication non-invasively in humans. In N-methyl-D-aspartate (NMDA) receptor antibody encephalitis, functional molecular assays are particularly important given the presence of NMDA antibodies in healthy populations, the multifarious symptomology and the lack of radiological signs. Recent advances in biophysical modelling techniques suggest that inferring cellular-level properties of neural circuits from macroscopic measures of brain activity is possible. Here, we estimated receptor function from EEG in patients with NMDA receptor antibody encephalitis (n = 29) as well as from encephalopathic and neurological patient controls (n = 36). We show that the autoimmune patients exhibit distinct fronto-parietal network changes from which ion channel estimates can be obtained using a microcircuit model. Specifically, a dynamic causal model of EEG data applied to spontaneous brain responses identifies a selective deficit in signalling at NMDA receptors in patients with NMDA receptor antibody encephalitis but not at other ionotropic receptors. Moreover, though these changes are observed across brain regions, these effects predominate at the NMDA receptors of excitatory neurons rather than at inhibitory interneurons. Given that EEG is a ubiquitously available clinical method, our findings suggest a unique re-purposing of EEG data as an assay of brain network dysfunction at the molecular level.

Type: Article
Title: Ion channels in EEG: isolating channel dysfunction in NMDA receptor antibody encephalitis
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/brain/awy107
Publisher version: https://doi.org/10.1093/brain/awy107
Language: English
Additional information: © The Author(s) (2018). Published by Oxford University Press on behalf of the Guarantors of Brain. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/).
Keywords: NMDA receptor antibody encephalitis, EEG, encephalopathy, dynamic causal modelling
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Imaging Neuroscience
URI: https://discovery.ucl.ac.uk/id/eprint/10057679
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