Of the symptoms associated with schizophrenia the deficit in filtering or gating of external sensory stimuli is researchable and lends itself to quantification and to pharmacological studies in animals and man. Several methods for the study of dysfunctional gating have been utilized and include repulse inhibition of acoustic startle (PPI startle) and cortical evoked responses using the P50 wave of the EEG (P50). None of these methods address the specific clinical external sensory deficits associated with schizophrenia. The thalamus is the first relay station where significant reduction of external sensory input can occur. Thus, information derived from the external sensory gating may define a subgroup of schizophrenic patients who show gating abnormalities theorized to be associated with thalamic dysfunction. Specific research aims will focus on: the development of an external sensory gating scale; specificity of gating deficits in psychiatric patients; sensory modality-specific aspects of gating deficits; concordance of measures of abnormal sensory gating as evaluated by the external sensory gating scale, PPI startle and P50 in schizophrenic patients; and the effect of compounds such as methamphetamine and ketamine on PPI startle, P50, and the external sensory gating scale.
