Debilitating deficits in attention, perception, and information processing are prominent features in individuals with schizophrenia .a number of theories suggest that schizophrenia is primarily a disease of disordered cognition, and that deficits in perception and attention are basic to the disorder and its symptoms. A central hypothesis, which has been proposed to account for these deficits is that schizophrenics cannot inhibit or 'gate' sensory input, leading to sensory inundation and an overload of information reaching consciousness. The two most commonly used physiological procedures to assess inhibitory mechanisms and test the gating hypothesis have been the auditory dual-click conditioning-testing (p50) and prepulse inhibition (PPI) of acoustic startle. Schizophrenics show less inhibition (or gating) in their p50 responses to the second stimulus and also have reduced amplitude to the first click. Similarly for PPI, schizophrenics have impaired inhibition of the acoustic startle response when it is preceded by a weaker auditory stimulus, compared to normal controls. These reports support hypotheses of neuronal hyperexcitability possibly related to a defect in inhibitory neuronal pathways, and are consistent with clinical observations of defective attention in schizophrenia. Schizophrenic patients have been characterized clinically by a constellation of positive, negative, and/or disorganized symptoms, but they also report perceptual abnormalities, which could be consistent with this kind of filtering deficit. Our laboratory has developed a structured clinical interview to record perceptual anomalies, which reflect sensory inundation and flooding by sensory stimuli. Self- reports of perceptual anomalies have face validity as behavioral exemplars of defective inhibitory mechanisms and sensory gating and would be expected to correlate with the physiological measures of sensory gating. No previous studies have assessed sensory gating as measured by p50and PPI and clinical reports of external sensory gating simultaneously and in the same subjects, and there is currently only one published report concurrently assessing p50 and PPI in human subjects. The purpose of this proposal is to test the meaning and significance of a sensory gating phenomenon in schizophrenia by assessing the correspondence among subjective assessments of perceptual anomalies using our structured clinical interview (siapa), and physiological measures (p50 and PPI) of sensory and sensorimotor inhibition, in normal controls and unmedicated individuals with schizophrenia, and to better characterize the sensory gating construct by relating these measures to neuropsychological function, and clinical measures including symptom profile, length of illness, chronicity, and insight.
