Ion channels in EEG: isolating channel dysfunction in NMDA receptor antibody encephalitis
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 anti...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
Oxford University Press
2018
|
| _version_ | 1826292991554224128 |
|---|---|
| author | Symmonds, M Moran, C Leite, M Buckley, C Irani, S Stephan, K Friston, K Moran, R |
| author_facet | Symmonds, M Moran, C Leite, M Buckley, C Irani, S Stephan, K Friston, K Moran, R |
| author_sort | Symmonds, M |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T03:23:13Z |
| format | Journal article |
| id | oxford-uuid:b82611af-8eb9-4910-911b-a556eddb656f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:23:13Z |
| publishDate | 2018 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | oxford-uuid:b82611af-8eb9-4910-911b-a556eddb656f2022-03-27T04:53:52ZIon channels in EEG: isolating channel dysfunction in NMDA receptor antibody encephalitisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b82611af-8eb9-4910-911b-a556eddb656fEnglishSymplectic Elements at OxfordOxford University Press2018Symmonds, MMoran, CLeite, MBuckley, CIrani, SStephan, KFriston, KMoran, RNeurological 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. |
| spellingShingle | Symmonds, M Moran, C Leite, M Buckley, C Irani, S Stephan, K Friston, K Moran, R Ion channels in EEG: isolating channel dysfunction in NMDA receptor antibody encephalitis |
| title | Ion channels in EEG: isolating channel dysfunction in NMDA receptor antibody encephalitis |
| title_full | Ion channels in EEG: isolating channel dysfunction in NMDA receptor antibody encephalitis |
| title_fullStr | Ion channels in EEG: isolating channel dysfunction in NMDA receptor antibody encephalitis |
| title_full_unstemmed | Ion channels in EEG: isolating channel dysfunction in NMDA receptor antibody encephalitis |
| title_short | Ion channels in EEG: isolating channel dysfunction in NMDA receptor antibody encephalitis |
| title_sort | ion channels in eeg isolating channel dysfunction in nmda receptor antibody encephalitis |
| work_keys_str_mv | AT symmondsm ionchannelsineegisolatingchanneldysfunctioninnmdareceptorantibodyencephalitis AT moranc ionchannelsineegisolatingchanneldysfunctioninnmdareceptorantibodyencephalitis AT leitem ionchannelsineegisolatingchanneldysfunctioninnmdareceptorantibodyencephalitis AT buckleyc ionchannelsineegisolatingchanneldysfunctioninnmdareceptorantibodyencephalitis AT iranis ionchannelsineegisolatingchanneldysfunctioninnmdareceptorantibodyencephalitis AT stephank ionchannelsineegisolatingchanneldysfunctioninnmdareceptorantibodyencephalitis AT fristonk ionchannelsineegisolatingchanneldysfunctioninnmdareceptorantibodyencephalitis AT moranr ionchannelsineegisolatingchanneldysfunctioninnmdareceptorantibodyencephalitis |