This 4 year project will develop, in a resource-efficient manner, a direct, stable, reliable and quantitative measure of sensory gating, and determine whether this measure detects gating deficits in clinical populations. Several disorders are characterized by symptoms that suggest the intrusion into consciousness of unwanted sensory information. Failures in the normal suppression (""""""""gating"""""""") of sensory information are associated with cognitive disturbances in schizophrenia, and with sensory tics and premonitory urges in Tourette Syndrome (TS). The biological basis for deficient sensory gating has been studied by """"""""surrogate"""""""" measures, in which a first stimulus inhibits (gates) the electrophysiological or motor response to a second stimulus (P50 gating, and prepulse inhibition of startle (PPI), respectively). These measures detect deficits in clinical populations, and are valuable in experimental models. Nonetheless, these surrogate measures do not directly assess the perceptual impact of deficient sensory gating as it is experienced by patients. In fact, little data supports the assumption that either P50 gating or PPI directly assess processes linked to an individual's perception of sensory information, or that deficits in these measures reflect dysfunction responsible for clinical symptoms. A measure that more directly assesses sensory gating, as it impacts perceptual experience, was first reported in 1939, and is termed """"""""prepulse inhibition of perceived stimulus intensity"""""""" (PPIPSI). PPIPSI is assessed by a direct report of the perceived intensity of a stimulus, in the presence and absence of a prestimulus. Under appropriate conditions, subjects report that they perceive an intense abrupt stimulus - a 118 dB noise burst, a 40 psi air puff, or a 170 V cutaneous shock - to be less intense if it is preceded by a weak prepulse. PPIPSI has received little attention as a measure of sensory gating, compared to more complex, surrogate measures (P50 suppression and PPI). This application will establish important, new information about PPIPSI, that will allow its use in systematic studies of sensory gating in normal and disordered populations. Studies will assess important features of PPIPSI, including: 1) stimulus parameters that elicit a full range of gating effects; 2) test-retest stability; 3) reliability across experimental settings; 4) generalizability across sensory modalities; 5) its sensitivity in children; and 6) the impact of attentional manipulations. Finally, preliminary studies will assess the utility of this measure in detecting deficits in patients with schizophrenia or TS - disorders characterized by symptoms of deficient sensory and motor inhibition, and by deficits in PPI.
