Reduced serial dependence suggests deficits in synaptic potentiation in anti-NMDAR encephalitis and schizophrenia

A mechanistic understanding of core cognitive processes, such as working memory, is crucial to addressing psychiatric symptoms in brain disorders. We propose a combined psychophysical and biophysical account of two symptomatologically related diseases, both linked to hypofunctional NMDARs: schizophr...

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Autores: Stein, Heike, Barbosa, João Moura, Rosa Justicia, Mireia, Prades-Senovilla, Laia, Morató, Alba, Galan-Gadea, Adria, Ariño Rodríguez, Helena, Martínez Hernández, Eugenia, Castro Fornieles, Josefina, Dalmau Obrador, Josep, Compte Braquets, Albert
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/172844
Acceso en línea:https://hdl.handle.net/2445/172844
Access Level:acceso abierto
Palabra clave:Memòria
Esquizofrènia
Encefalitis
Memory
Schizophrenia
Encephalitis
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spelling Reduced serial dependence suggests deficits in synaptic potentiation in anti-NMDAR encephalitis and schizophreniaStein, HeikeBarbosa, João MouraRosa Justicia, MireiaPrades-Senovilla, LaiaMorató, AlbaGalan-Gadea, AdriaAriño Rodríguez, HelenaMartínez Hernández, EugeniaCastro Fornieles, JosefinaDalmau Obrador, JosepCompte Braquets, AlbertMemòriaEsquizofrèniaEncefalitisMemorySchizophreniaEncephalitisA mechanistic understanding of core cognitive processes, such as working memory, is crucial to addressing psychiatric symptoms in brain disorders. We propose a combined psychophysical and biophysical account of two symptomatologically related diseases, both linked to hypofunctional NMDARs: schizophrenia and autoimmune anti-NMDAR encephalitis. We first quantified shared working memory alterations in a delayed-response task. In both patient groups, we report a markedly reduced influence of previous stimuli on working memory contents, despite preserved memory precision. We then simulated this finding with NMDAR-dependent synaptic alterations in a microcircuit model of prefrontal cortex. Changes in cortical excitation destabilized within-trial memory maintenance and could not account for disrupted serial dependence in working memory. Rather, a quantitative fit between data and simulations supports alterations of an NMDAR-dependent memory mechanism operating on longer timescales, such as short-term potentiation.Nature Publishing Group2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/172844Articles publicats en revistes (Medicina)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1038/s41467-020-18033-3Nature Communications, 2020, vol. 11, num. 1, p. 4250https://doi.org/10.1038/s41467-020-18033-3info:eu-repo/grantAgreement/EC/H2020/713673cc-by (c) Stein, Heike et al., 2020http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1728442026-05-27T06:46:51Z
dc.title.none.fl_str_mv Reduced serial dependence suggests deficits in synaptic potentiation in anti-NMDAR encephalitis and schizophrenia
title Reduced serial dependence suggests deficits in synaptic potentiation in anti-NMDAR encephalitis and schizophrenia
spellingShingle Reduced serial dependence suggests deficits in synaptic potentiation in anti-NMDAR encephalitis and schizophrenia
Stein, Heike
Memòria
Esquizofrènia
Encefalitis
Memory
Schizophrenia
Encephalitis
title_short Reduced serial dependence suggests deficits in synaptic potentiation in anti-NMDAR encephalitis and schizophrenia
title_full Reduced serial dependence suggests deficits in synaptic potentiation in anti-NMDAR encephalitis and schizophrenia
title_fullStr Reduced serial dependence suggests deficits in synaptic potentiation in anti-NMDAR encephalitis and schizophrenia
title_full_unstemmed Reduced serial dependence suggests deficits in synaptic potentiation in anti-NMDAR encephalitis and schizophrenia
title_sort Reduced serial dependence suggests deficits in synaptic potentiation in anti-NMDAR encephalitis and schizophrenia
dc.creator.none.fl_str_mv Stein, Heike
Barbosa, João Moura
Rosa Justicia, Mireia
Prades-Senovilla, Laia
Morató, Alba
Galan-Gadea, Adria
Ariño Rodríguez, Helena
Martínez Hernández, Eugenia
Castro Fornieles, Josefina
Dalmau Obrador, Josep
Compte Braquets, Albert
author Stein, Heike
author_facet Stein, Heike
Barbosa, João Moura
Rosa Justicia, Mireia
Prades-Senovilla, Laia
Morató, Alba
Galan-Gadea, Adria
Ariño Rodríguez, Helena
Martínez Hernández, Eugenia
Castro Fornieles, Josefina
Dalmau Obrador, Josep
Compte Braquets, Albert
author_role author
author2 Barbosa, João Moura
Rosa Justicia, Mireia
Prades-Senovilla, Laia
Morató, Alba
Galan-Gadea, Adria
Ariño Rodríguez, Helena
Martínez Hernández, Eugenia
Castro Fornieles, Josefina
Dalmau Obrador, Josep
Compte Braquets, Albert
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Memòria
Esquizofrènia
Encefalitis
Memory
Schizophrenia
Encephalitis
topic Memòria
Esquizofrènia
Encefalitis
Memory
Schizophrenia
Encephalitis
description A mechanistic understanding of core cognitive processes, such as working memory, is crucial to addressing psychiatric symptoms in brain disorders. We propose a combined psychophysical and biophysical account of two symptomatologically related diseases, both linked to hypofunctional NMDARs: schizophrenia and autoimmune anti-NMDAR encephalitis. We first quantified shared working memory alterations in a delayed-response task. In both patient groups, we report a markedly reduced influence of previous stimuli on working memory contents, despite preserved memory precision. We then simulated this finding with NMDAR-dependent synaptic alterations in a microcircuit model of prefrontal cortex. Changes in cortical excitation destabilized within-trial memory maintenance and could not account for disrupted serial dependence in working memory. Rather, a quantitative fit between data and simulations supports alterations of an NMDAR-dependent memory mechanism operating on longer timescales, such as short-term potentiation.
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/172844
url https://hdl.handle.net/2445/172844
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1038/s41467-020-18033-3
Nature Communications, 2020, vol. 11, num. 1, p. 4250
https://doi.org/10.1038/s41467-020-18033-3
info:eu-repo/grantAgreement/EC/H2020/713673
dc.rights.none.fl_str_mv cc-by (c) Stein, Heike et al., 2020
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Stein, Heike et al., 2020
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv Articles publicats en revistes (Medicina)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.300719

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