Schizophrenia is associated with a fundamental deficit in selectivity that operates at all levels of information processing from basic sensory to higher order semantic processing. However the neurobiological bases of these deficits and their modulation through the course of the disease has not been established. We propose a series of studies that assess information selection deficits in schizophrenia within the framework of a multistage model, comprising an initial stage of sensory filtering or gating, a subsequent stage of sensory discrimination and memory processing, and a final stage of response selection. Parallel experiments will examine the functional and structural substrates of attention deficits in schizophrenia, using converging evidence from behavioral, electrophysiological (ERP) and functional Magnetic Resonance Imaging (fMRI) techniques. Electrophysiological (event-related potential, or ERP) studies will compare ERPs evoked in sensory gating, automatic and voluntary attention allocation, and response selection tasks in groups of schizophrenic patients and healthy controls. These studies will document ERP abnormalities at each level of processing previously observed in schizophrenic patients by the PI and her colleagues. Functional magnetic resonance imaging (functional MRI, or fMRI) studies will then be conducted using the same tasks and patterns of activation will be compared in healthy and schizophrenic subjects. Event-related fMRI analysis will be used to isolate activations evoked by task relevant and irrelevant stimuli. Group differences in activation patterns will be used to identify critical brain regions engaged at these levels of stimulus and response selection. The clinical objective of the proposed studies is to relate selective attention deficits in schizophrenia to symptomatology and chronicity of this illness. Information from these studies will further our understanding of the functional and structural basis of distractibility and information processing deficits in schizophrenia.
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