NMDA-receptor antibodies alter cortical microcircuit dynamics

Rosch, R. E.; Wright, S.; Cooray, G.; Papadopoulou, M.; Goyal, S.; Lim, M.; Vincent, A.; Upton, L. A.; Baldeweg, T.; Friston, K. J.

doi:10.1101/160309

bioRxiv · 10.1101/160309

NMDA-receptor antibodies alter cortical microcircuit dynamics

Rosch, R. E.·Wright, S.·Cooray, G.·Papadopoulou, M.·Goyal, S.·Lim, M.·Vincent, A.·Upton, L. A.·Baldeweg, T.·Friston, K. J.

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Abstract

NMDA-receptor antibodies (NMDAR-Ab) cause an autoimmune encephalitis with a diverse range of electroencephalographic (EEG) abnormalities. NMDAR-Ab are believed to disrupt receptor function, but how blocking this excitatory neurotransmitter can lead to paroxysmal EEG abnormalities - or even seizures - is poorly understood. Here, we show that NMDAR-Ab change intrinsic cortical connections and neuronal population dynamics to alter the spectral composition of spontaneous EEG activity, and predispose to paroxysmal EEG 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 paediatric patients with NMDAR-Ab encephalitis. Finally, we use the mouse model to show that NMDAR-Ab- related changes render microcircuitry critically susceptible to overt EEG paroxysms, when these key parameters are changed. These findings offer mechanistic insights into circuit-level dysfunction induced by NMDAR-Ab.

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Rosch, R. E., Wright, S., Cooray, G., Papadopoulou, M., Goyal, S., Lim, M., Vincent, A., Upton, L. A., Baldeweg, T., Friston, K. J.. 2017-07-07. NMDA-receptor antibodies alter cortical microcircuit dynamics. https://doi.org/10.1101/160309

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