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

Mkael Symmonds, Catherine H. Moran, M. Isabel Leite, Camilla Buckley, Sarosh R. Irani, Klaas Enno Stephan, Karl J. Friston, Rosalyn J. Moran*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

16 Citations (Scopus)

Abstract

See Roberts and Breakspear (doi:10.1093/brain/awy136) for a scientific commentary on this article. 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.

Original languageEnglish
Pages (from-to)1691-1702
Number of pages12
JournalBrain
Volume141
Issue number6
Early online date30 Apr 2018
DOIs
Publication statusPublished - 1 Jun 2018

Keywords

  • dynamic causal modelling
  • EEG
  • encephalopathy
  • NMDA receptor antibody encephalitis

Fingerprint Dive into the research topics of 'Ion channels in EEG: Isolating channel dysfunction in NMDA receptor antibody encephalitis'. Together they form a unique fingerprint.

Cite this