NMDA-receptor antibodies alter cortical microcircuit dynamics

Rosch, Richard; Wright, Sukhvir; Cooray, Gerald; Papadopoulou, Margarita; Goyal, Sushma; Lim, Ming; Vincent, Angela; Upton, Amy L.; Baldeweg, Torsten; Friston, Karl J.

doi:10.1073/pnas.1804846115

Cited by 43 publications

(32 citation statements)

References 66 publications

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“…Anti-NMDA receptor encephalitis is a major type of autoimmune encephalitis; anti-NMDA receptor antibodies cause internalization of surface NMDA receptors, resulting in a decrease in receptor density on the cellular surface [61][62][63][64]. Previous studies in rodents provided no evidence that NMDA antagonists elicit seizures [65,66], and anti-NMDA encephalitis seems controversial in the light of positive results with NMDA antagonists in rodent studies [67][68][69][70]. However, it has been documented that D-CPP-ene, a competitive NMDA antagonist, worsened seizures in 3/8 patients with epilepsy in a clinical study [21], suggesting that acute reduction of NMDA receptor function may result in an excitatory and inhibitory imbalance.…”

Section: Anti-nmda Antibody Encephalitismentioning

confidence: 99%

Ionotropic Glutamate Receptors in Epilepsy: A Review Focusing on AMPA and NMDA Receptors

2020

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It is widely accepted that glutamate-mediated neuronal hyperexcitation plays a causative role in eliciting seizures. Among glutamate receptors, the roles of N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors in physiological and pathological conditions represent major clinical research targets. It is well known that agonists of NMDA or AMPA receptors can elicit seizures in animal or human subjects, while antagonists have been shown to inhibit seizures in animal models, suggesting a potential role for NMDA and AMPA receptor antagonists in anti-seizure drug development. Several such drugs have been evaluated in clinical studies; however, the majority, mainly NMDA-receptor antagonists, failed to demonstrate adequate efficacy and safety for therapeutic use, and only an AMPA-receptor antagonist, perampanel, has been approved for the treatment of some forms of epilepsy. These results suggest that a misunderstanding of the role of each glutamate receptor in the ictogenic process may underlie the failure of these drugs to demonstrate clinical efficacy and safety. Accumulating knowledge of both NMDA and AMPA receptors, including pathological gene mutations, roles in autoimmune epilepsy, and evidence from drug-discovery research and pharmacological studies, may provide valuable information enabling the roles of both receptors in ictogenesis to be reconsidered. This review aimed to integrate information from several studies in order to further elucidate the specific roles of NMDA and AMPA receptors in epilepsy.

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Section: Anti-nmda Antibody Encephalitismentioning

confidence: 99%

Ionotropic Glutamate Receptors in Epilepsy: A Review Focusing on AMPA and NMDA Receptors

2020

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“…Recently, DCM for neuroimaging has been extended to accommodate fusion of several different imaging modalities 87 . This raises the possibility of fusing immunological and neurobiological DCMs, to model conditions—like multiple sclerosis 88 , 89 or autoimmune encephalitides 90 —in which the immune and nervous systems interact. Here the aim would be to generate both neurophysiological and immunological measurements.…”

Section: Discussionmentioning

confidence: 99%

Dynamic causal modelling of immune heterogeneity

Parr

Bhat

Zeidman

et al. 2021

Sci Rep

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An interesting inference drawn by some COVID-19 epidemiological models is that there exists a proportion of the population who are not susceptible to infection—even at the start of the current pandemic. This paper introduces a model of the immune response to a virus. This is based upon the same sort of mean-field dynamics as used in epidemiology. However, in place of the location, clinical status, and other attributes of people in an epidemiological model, we consider the state of a virus, B and T-lymphocytes, and the antibodies they generate. Our aim is to formalise some key hypotheses as to the mechanism of resistance. We present a series of simple simulations illustrating changes to the dynamics of the immune response under these hypotheses. These include attenuated viral cell entry, pre-existing cross-reactive humoral (antibody-mediated) immunity, and enhanced T-cell dependent immunity. Finally, we illustrate the potential application of this sort of model by illustrating variational inversion (using simulated data) of this model to illustrate its use in testing hypotheses. In principle, this furnishes a fast and efficient immunological assay—based on sequential serology—that provides a (1) quantitative measure of latent immunological responses and (2) a Bayes optimal classification of the different kinds of immunological response (c.f., glucose tolerance tests used to test for insulin resistance). This may be especially useful in assessing SARS-CoV-2 vaccines.

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“…This ensured the neural mass model has construct validity in relation to the compartmental model. DCM approach has been used to infer changes in synaptic plasticity in large cortical networks 17 in healthy and clinical populations 19 among other applications. It exploits the stationarity of variance of neuronal firing over the course of the task to efficiently fit neural mass models to MEG data.…”

Section: Resultsmentioning

confidence: 99%

Differences in visually induced MEG oscillations reflect differences in deep cortical layer activity

Pinotsis

Miller

2020

Commun Biol

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Neural activity is organized at multiple scales, ranging from the cellular to the whole brain level. Connecting neural dynamics at different scales is important for understanding brain pathology. Neurological diseases and disorders arise from interactions between factors that are expressed in multiple scales. Here, we suggest a new way to link microscopic and macroscopic dynamics through combinations of computational models. This exploits results from statistical decision theory and Bayesian inference. To validate our approach, we used two independent MEG datasets. In both, we found that variability in visually induced oscillations recorded from different people in simple visual perception tasks resulted from differences in the level of inhibition specific to deep cortical layers. This suggests differences in feedback to sensory areas and each subject’s hypotheses about sensations due to differences in their prior experience. Our approach provides a new link between non-invasive brain imaging data, laminar dynamics and top-down control.

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NMDA-receptor antibodies alter cortical microcircuit dynamics

Cited by 43 publications

References 66 publications

Ionotropic Glutamate Receptors in Epilepsy: A Review Focusing on AMPA and NMDA Receptors

Ionotropic Glutamate Receptors in Epilepsy: A Review Focusing on AMPA and NMDA Receptors

Dynamic causal modelling of immune heterogeneity

Differences in visually induced MEG oscillations reflect differences in deep cortical layer activity

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