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Reduced Parahippocampal Connectivity Produces Schizophrenia-like Memory Deficits in Simulated Neural Circuits With Reduced Parahippocampal Connectivity
Lucia M. Talamini, PhD;
Martijn Meeter, PhD;
Brita Elvevåg, PhD;
Jaap M. J. Murre, PhD;
Terry E. Goldberg, PhD
Arch Gen Psychiatry. 2005;62:485-493.
Context Episodic memory impairments are well characterized in schizophrenia, but their neural origin is unclear.
Objective To determine whether the episodic memory impairments in schizophrenia may originate from reduced parahippocampal connectivity.
Design Experimental in silico model.
Setting Department of Psychology, University of Amsterdam, Amsterdam, the Netherlands.
Interventions A new, in silico medial temporal lobe model that simulates normal performance on a variety of episodic memory tasks was devised. The effects of reducing parahippocampal connectivity in the model (from perirhinal and parahippocampal cortex to entorhinal cortex and from entorhinal cortex to hippocampus) were evaluated and compared with findings in schizophrenic patients. Alternative in silico neuropathologies, increased noise and loss of hippocampal neurons, were also evaluated.
Results In the model, parahippocampal processing subserves integration of different cortical inputs to the hippocampus and feature extraction during recall. Reduced connectivity in this area resulted in a pattern of deficits that closely mimicked the impairments in schizophrenia, including a mild recognition impairment and a more severe impairment in free recall. Furthermore, the schizophrenic model was not differentially sensitive to interference, also consistent with behavioral data. Notably, neither increased noise levels nor a reduction of hippocampal nodes in the model reproduced this characteristic memory profile.
Conclusions Taken together, these findings highlight the importance of parahippocampal neuropathology in schizophrenia, demonstrating that reduced connectivity in this region may underlie episodic memory problems associated with the disorder.
Author Affiliations: Department of Psychology, University of Amsterdam, Amsterdam, the Netherlands (Drs Talamini, Meeter, and Murre); Division of CNS-Psychiatry I, Johnson & Johnson PR&D, Beerse, Belgium (Dr Talamini); and Clinical Brain Disorders Branch, National Institute of Mental Health, Bethesda, Md (Drs Elvevåg and Goldberg).
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