Computational Modeling of Contrast Sensitivity and Orientation Tuning in First-Episode and Chronic Schizophrenia

摘要

Computational modeling is a useful method for generating hypotheses about the contributions of impaired neurobiological mechanisms, and their interactions, to psychopathology. Modeling is being increasingly used to further our understanding of schizophrenia, but to date, it has not been applied to questions regarding the common perceptual disturbances in the disorder. In this article, we model aspects of low-level visual processing and demonstrate how this can lead to testable hypotheses about both the nature of visual abnormalities in schizophrenia and the relationships between the mechanisms underlying these disturbances and psychotic symptoms. Using a model that incorporates retinal, lateral geniculate nucleus (LGN), and V1 activity, as well as gain control in the LGN, homeostatic adaptation in V1, lateral excitation and inhibition in V1, and self-organization of synaptic weights based on Hebbian learning and divisive normalization, we show that (a) prior data indicating increased contrast sensitivity for low-spatial-frequency stimuli in first-episode schizophrenia can be successfully modeled as a function of reduced retinal and LGN efferent activity, leading to overamplification at the cortical level, and (b) prior data on reduced contrast sensitivity and broadened orientation tuning in chronic schizophrenia can be successfully modeled by a combination of reduced V1 lateral inhibition and an increase in the Hebbian learning rate at V1 synapses for LGN input. These models are consistent with many current findings, and they predict several relationships that have not yet been demonstrated. They also have implications for understanding changes in brain and visual function from the first psychotic episode to the chronic stage of illness.