ELECTROPHYSIOLOGY OF STIMULUS PROCESSING &ENCODING IN SCHIZOPHRENIA

University Of Pennsylvania, Philadelphia PA

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Abstract

DESCRIPTION (provided by applicant): Patients with schizophrenia exhibit a variety of behavioral and physiological impairments in the perception, modulation and evaluation of environmental stimuli. These information processing deficits disrupt patients' efforts to appropriately interpret and assign salience to incoming stimuli, resulting in disturbances in subsequent behavioral response formulation. The range of deficits extends from the earliest pre-attentive stages of information processing to relatively late higher-cortical processes, including memory encoding and storage. However, the precise nature of these deficits, and how impairments in different components of stimulus processing might relate to one another, remains unclear. Are there, for instance, differential deficits in one or more of these components, perhaps during early stimulus perception, that account for subsequent deficits? Might there be differential impairment of processes that facilitate response to novel or salient stimuli, relative to those that inhibit responses to repetitive or irrelevant stimuli? Are there different profiles of deficits evident in different sets of patients, that might distinguish Deficit from Nondeficit or male from female patients? This last would support the idea that schizophrenia is a heterogeneous set of disorders, rather than a single entity. We will employ electrophysiological methods to assess multiple aspects of information processing within the same subjects. A total of 80 patients and 80 controls will be studied. Tasks will include P50 sensory gating, prepulse inhibition of startle, simple sensory perception, mismatch negativity, P300 target and deviant responses, N-back working memory and recognition memory, in both auditory and visual modalities. The interrelationships among specific processing deficits, and the relationship of deficit profiles to clinical, demographic and neuropsychological variables will be considered. Event-related potentials (ERPs), with their exquisite temporal resolution, permit a fine dissection of the various stimulus processing stages and components, permitting independent and correlative analyses. Findings from this project will be integrated with the fMRI data from Project II, to provide both temporal and spatial specificity for observed deficits in patients. These will similarly integrated with those from Projects III, IV and V, to identify more precise neural circuit and neurochemical deficits.