title: A computational model for spatial working memory deficits in schizophrenia.
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 network mimic the behavioral results for schizophrenic patients. Thus, dynamics in our model network support a role of both global inhibition reduction and hypofunctional NMDA receptors in interneurons in generating the behavioral deficits of simple spatial working memory tasks in schizophrenia.
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Cano-Colino
authors.forename: A
authors.initials: A
authors.lastname: Compte
mesh_terms: D000465:Algorithms; D000818:Animals; D003198:Computer Simulation; D003463:Cues; D055724:Electrophysiological Phenomena; D005403:Fixation, Ocular / Q000502:physiology; D000882:Haplorhini; D007395:Interneurons / Q000502:physiology; D015640:Ion Channel Gating / Q000502:physiology; D008569:Memory Disorders / Q000209:etiology / Q000523:psychology*; D008570:Memory, Short-Term / Q000502:physiology*; D008959:Models, Neurological; D018091:Receptors, AMPA / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D012565:Schizophrenic Psychology; D013028:Space Perception / Q000502:physiology*
chemical_list: D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate