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Alexander Schielke, Bart Krekelberg; Behavioral and Neural Changes in Early Visual Processing in an Animal Model of Schizophrenia. Journal of Vision 2018;18(10):32. doi: https://doi.org/10.1167/18.10.32.
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© ARVO (1962-2015); The Authors (2016-present)
Schizophrenia (Sz) affects about 1% of the population. Alterations of visual perception are frequently reported in schizophrenia. They offer information on disease progression and severity beyond what can be gathered through traditional neuropsychological tests alone. In line with established theories of Sz, we hypothesize that NMDA-receptor hypofunction might underlie changes in visual processing. To test this hypothesis, we are developing a nonhuman primate model to quantify both visual perception and its underlying neural mechanisms. To test the NMDA hypofunction hypothesis, we injected rhesus monkeys (M. mulatta) either with an intramuscular injection of a sub anesthetic dose of the NMDA-receptor antagonist ketamine (0.3 mg/kg), or with saline (control). We performed behavioral experiments to quantify visual perception and multi-electrode array recordings in V1 to document neural response changes. In the behavioral experiments, we quantified the strength of a contrast-contrast illusion: in healthy human subjects, the perceived contrast of a grating is reduced by its surround, patients with Sz are less susceptible to this so-called Chubb illusion. In each trial, we presented two gratings with variable contrasts and with or without surrounds. The monkey's behavior reflected a clear Chubb illusion. Consistent with the NMDA hypofunction hypothesis, the strength of the illusion was reduced after the injection of ketamine. In the electrophysiology experiments, we investigated neuronal gain, which is thought to be reduced in Sz. We presented whole-field visual flicker to quantify the steady state visual response gain and found that ketamine injections led to an overall reduction in the gain. Our current efforts are focused on corroborating these findings in additional animals and on performing simultaneous behavioral and electrophysiological recordings to establish a direct link between neural and behavioral responses.
Meeting abstract presented at VSS 2018
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