Stein, HeikeBarbosa, João MouraRosa Justicia, MireiaPrades-Senovilla, LaiaMorató, AlbaGalan-Gadea, AdriaAriño Rodríguez, HelenaMartínez Hernández, EugeniaCastro Fornieles, JosefinaDalmau Obrador, JosepCompte Braquets, Albert2020-12-172020-12-172020-08-252041-1723https://hdl.handle.net/2445/172844A 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.12 p.application/pdfengcc-by (c) Stein, Heike et al., 2020http://creativecommons.org/licenses/by/3.0/esMemòriaEsquizofrèniaEncefalitisMemorySchizophreniaEncephalitisinfo:eu-repo/semantics/article7053012020-12-17info:eu-repo/semantics/openAccess798006332843635