Early Cortical Processing In Schizophrenia

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Schizophrenia has traditionally been associated with deficits in high order processing involving cortical regions such as prefrontal or temporohippocampal brain regions. More recently, however, dysfunction of early stages of sensory processing have been demonstrated as well. In the auditory system, schizophrenia patients show impaired generation of mismatch negativity (MMN), an index of neurophysiological dysfunction at the level of auditory sensory cortex, along with impaired generation of auditory N1. Deficits in MMN generation correlate with deficits in performance on tests of tone matching, reflecting impaired auditory sensory memory(ASM) performance. Similar deficits have now been documented in the visual system. Thus, patients with schizophrenia show impaired ability to close fragmented images, reflecting dysfunction at the level of lateral occipital cortex (LO). In addition, amplitude of the P1 visual component is reduced over dorsal stream regions, whereas amplitudes of the ventral stream P1 and N1 components are relatively intact. Visual findings are consistent with impaired visual processing particularly within the magnocellular visual pathway and with impaired dorsal/ventral system interaction. The overall goals of the present study are to further define mechanisms of neurophysiological dysfunction within the auditory and visual systems deficits and to evaluate the degree to which a single underlying deficit (e.g., NMDA dysfunction) could account for the pattern of dysfunction observed. Finally, this project will begin to evaluate the degree to which separate deficits in auditory and visual processing lead to impairments in higher order processes. Relevance to public health: Schizophrenia is a severe mental disorder that affects up to 1% of the population worldwide. Deficits in cognitive function predict poor out come and continued disability. This project will analyze neural basis of cognitive dysfunction.