A computational model for spatial working memory deficits in schizophrenia

Pharmacopsychiatry
M Cano-Colino, A Compte

Abstract

Cognitive deficits in schizophrenia have been hypothesized to be caused by altered synaptic transmission in circuits of the prefrontal cortex. 2 main hypotheses have been put forward: reduced inhibition and hypofunctional NMDA receptors. Recently, Lee et al. (2008) found that spatial working memory deficits in schizophrenic patients include a disproportionately high incidence of high-confidence error responses. Here, we have studied what synaptic dysfunction can generate this specific behavioral deficit using a computational network model of spatial working memory. We developed quantitative behavioral readout from our network simulations, which reflected the qualitative properties of underlying neural dynamics. We then analyzed the behavioral effect of the GABAergic and glutamatergic hypotheses on our network simulations. We found that reduction in inhibitory transmission in the network caused a reduction in performance through an increase of high-confidence errors, as in the experimental data. In contrast, a concerted reduction in NMDA-receptor-dependent transmission reduced performance via increased low-confidence errors. Only when NMDA receptors were specifically depleted in interneurons did the behavioral read-out of our ne...Continue Reading

Citations

Jul 28, 2013·CPT: Pharmacometrics & Systems Pharmacology·H GeertsA Spiros
Oct 22, 2014·Schizophrenia Bulletin·Rodrigo PavãoOlavo B Amaral
May 12, 2015·Clinical Psychological Science : a Journal of the Association for Psychological Science·Alan AnticevicDeanna M Barch
Apr 20, 2019·PLoS Computational Biology·Alexander SeeholzerWulfram Gerstner
Jul 4, 2020·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Quentin J M HuysMichael J Frank

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