Schizophrenic patients have been shown to respond abnormally to sensory stimulation. They show a lack of prepulse inhibition (PPI) and a deficit of habituation of the acoustic startle reflex that have been interpreted as an inability to filter of gate sensory input. However, whether the PPI and habituation impairments are related to abnormal sensory processing is unclear. In addition, whether these deficits occur in all or only in a subgroup of schizophrenics has not been investigated. This proposal specifically outlines studies in human subjects that will investigate how sensory processing may relate to the PPI and habituation impairments that may underlie the cognitive fragmentation and thought disorder characteristic of schizophrenic patients. We will also assess the generality versus the specificity to a subgroup of schizophrenic patients of our results as it may relate to the heterogeneity of the schizophrenic disorder. Brainstem and middle latency auditory evoked potentials (BAEP and MAEP, respectively) will be used to explore the functioning of the auditory neural system. BAEP measures will test the integrity of the auditory periphery and of the brainstem functioning, whereas MAEP measures will explore auditory processing central to the brainstem up to the auditory cortex. Electromyographic recordings will be used to monitor the blink reflex component of the startle reaction. PPI will be induced by presenting weak prestimuli at short intervals prior to the startle stimulus, and habituation by presenting the same startle stimulus repeatedly, Auditory sensory functioning will be evaluated in a parametric study of BAEP and MAEP. Our main objective is to investigate the following questions: Are sensory gating and habituation deficits characteristic off all or a subgroup of schizophrenic patients? Do schizophrenic individuals with impairments in prepulse inhibition or habituation have abnormal auditory sensory processing?