Behavioural Brain Research 162 (2005) 256–263 Research report On the feasibility to detect and to quantify prepulse-elicited reaction in prepulse inhibition of the acoustic startle reflex in humans  Philipp A. Csomor a , Franz X. Vollenweider a , Joram Feldon b , Benjamin K. Yee b,∗ a Psychiatric University Hospital Zurich, Lenggstrasse 31, CH-8029 Zurich, Switzerland b LaboratoryofBehaviouralNeurobiology,SwissFederalInstituteofTechnology,Zurich,Schorenstrasse16,CH-8603Schwerzenbach,Switzerland Received 31 January 2005; received in revised form 20 March 2005; accepted 24 March 2005 Available online 28 April 2005 Abstract The possibility that the prepulse stimulus typically employed in the studies of prepulse inhibition (PPI) can produce observable response has been questioned recently. Conflicting reports range from observations of prepulse-elicited startle reaction to a complete lack of detectable prepulse-elicited reactions in healthy volunteers. This controversy is subjected to critical examination in the present study. The ability of prepulse stimuli to induce PPI and to elicit measurable responses was examined in two separate experiments using prepulses ranging from 6 to 18 dB above background (experiment 1), or 1 to 5 dB above background (experiment 2). Three levels of pulse stimulus were employed: 95, 105 and 115 dB A . Clear PPI and prepulse-elicited reaction were obtained in experiment 1, while neither effect was evident in experiment 2. Non-startle-eliciting prepulses that are of sufficient intensities to induce reliable PPI are associated with detectable and quantifiable response, confirming that direct evaluation of prepulse-processing is feasible and practical. This provides an additional measure of theoretical and potentially clinical relevance to PPI, and it ought to be included in future studies in patients as well as healthy subjects. © 2005 Elsevier B.V. All rights reserved. Keywords: Attention; Prepulse inhibition; Schizophrenia; Sensorimotor gating; Prepulse detection; Startle; Human 1. Introduction Prepulse inhibition (PPI) refers to the attenuation of the reflexive startle reaction towards an intense pulse stimulus when its presentation is shortly preceded by a weak prepulse stimulus [20,27]. PPI deficiency has been noted in a number of psychiatric conditions that are characterized by a general reduction of the ability to gate intrusive sensory, motor or cog- nitive information, for example in schizophrenia, schizotypal personality disorder, obsessive compulsive disorder, Hunt- ington’s disease and Tourette’s syndrome [7,12,29,30,36]. As a robust translational behavioural assay of sensorimotor gat- ing across the species, the PPI paradigm can be applied to invertebrate [19] and to all standard laboratory mammals in- cluding mice and rats, as effective as in human subjects [28].  The present report has been presented in abstract form at the Zurich Neuroscience Centre Meeting, Zurich, 2004. ∗ Corresponding author. Tel.: +41 1 6557417; fax: +41 1 6557203. E-mailaddress: benjamin.yee@behav.biol.ethz.ch (B.K. Yee). The expression of PPI is believed to involve active in- hibitory processes initiated by the perception and/or process- ing of the prepulse stimulus, and represents a form of early attentional control, which may be instrumental in preventing sensory overload. According to Graham [20–22] and Braff et al. [7], the nature of this inhibition is to protect the on-going processing of the prepulse stimulus from interference by the succeeding pulse stimulus. Thus, the magnitude of this inhi- bition (i.e., PPI) is assessed by the degree of startle reduction in prepulse-plus-pulse trials relative to pulse-alone trials. Although the focus of interest is on a presumably prepulse-initiated early attentional gating process, few attempts [1,14,25,37], until recently, have been made to directly assess the reaction to, or processing of, the prepulse (with the aim to identify and characterize the associated ini- tiation and execution of the inhibitory processes) in relation to the expression of PPI. It has been known that without altering the physical properties of the prepulse, manipulation designed to influence the perception of the prepulse stimulus, such as verbal instructions to attend or to ignore the prepulse 0166-4328/$ – see front matter © 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.bbr.2005.03.020