Experimental modification of P 50 suppression

White and Yee~1997! found that normal suppression of the P50 component of the event-related potential was disrupted during a paired-click paradigm when nonpsychiatric subjects performed mental arithmetic ~MA ! problems aloud, concurrently with the presentation of auditory stimuli. In fact, the degree of disruption reflected in the P50 suppression ratio fell within the range that is typically observed in schizophrenia patients. The present study was conducted to clarify the processes that might underlie the apparent disruption of P50 suppression during performance of an oral MA task. Participants completed a series of tasks designed to examine the impact of competing cognitive activity, competing auditory stimulation, muscle activity, and acute psychological stress on P50 amplitude and P50 suppression. Results suggested that psychological stress and heightened facial muscle activity may exert modulatory effects on P50 suppression. Descriptors: P50, Sensory gating, Psychological stressor, Mental arithmetic task, Schizophrenia Studies conducted on the P50 component of the auditory eventrelated potential ~ERP! have generated considerable research interest, as there is some evidence that P50 suppression may be a viable psychophysiological marker of vulnerability for schizophrenia ~e.g., Freedman et al., 1997 ! Schizophrenia patients and their biological relatives typically fail to exhibit a reduced response to a second auditory click~“Click 2” ! when presentation of this stimulus is preceded by a first click ~“Click 1” ! at an interclick interval of 500 ms. In contrast, nonpsychiatric subjects who are assumed to have intact filtering or gating processes generally exhibit a suppressed P50 to Click 2 ~e.g., Adler et al., 1982; Judd, McAdams, Budnick, & Braff, 1992; Yee, Nuechterlein, Morris, & White, 1998! Theorists have argued that the first auditory stimulus activates an inhibitory mechanism that protects processing of this initial stimulus from the potentially disruptive effects associated with the occurrence of subsequent, rapidly succeeding stimuli ~see discussions by Freedman et al., 1987, 1994; Leonard et al., 1996 ! Although inhibitory effects on P50 were initially hypothesized to be largely automatic or preattentive and to primarily reflect neuronal rather than psychological phenomena ~e.g., Freedman et al., 1987! , experimental manipulations have been found to influence P50 and its suppression. Research by Guterman, Josiassen, and Bashore~1992! , for instance, suggests that inhibitory effects on P50 suppression in nonpsychiatric subjects may be altered transiently by manipulating voluntary attention. Utilizing a different set of paradigms, however, other researchers have not observed this effect ~Jerger, Biggins, & Fein, 1992; White & Yee, 1997! A potential explanation for this discrepancy is that different aspects or degrees of attention may have been engaged across studies. Laboratory stressors also have been found to influence inhibiry effects on P50. Johnson and Adler ~1993! demonstrated that a cold pressor manipulation can disrupt P50 suppression in normal control subjects. Relying upon a behavioral manipulation, Waldo and Freedman ~1986! instructed nonpsychiatric subjects to perform a silent mental arithmetic ~MA ! task while listening to paired clicks. Although the MA task did not alter the P50 ratio, there was some suggestion that P50 suppression was reduced in subjects who reported increased anxiety. White and Yee ~1997! also directed nonpsychiatric subjects to engage in an MA task, concurrent with the P50 paired click paradigm, but the MA problems were performed aloud rather than silently. In addition, subjects were corrected when an incorrect response was provided and were periodically instructed to increase the speed of their performance. Under these more demanding conditions, the degree of disruption in P50 suppression, as indexed by the P50 ratio score, was of a similar magnitude to that obtained in outpatients diagnosed with schizophrenia ~e.g., Ward et al., 1996; Yee et al., 1998 ! These data are largely consistent with current models that have been offered to account for the neuronal mechanisms that potentially underlie P50 suppression and its impairment. Freedman and colleagues~Leonard et al., 1996 ! propose that gating of the P50 wave involves interneuron inhibition of pyramidal cells through GABAergic and other inhibitory synapses. Because interneurons and pyramidal neurons also receive cholinergic input from the septum, blockade of the septal cholinergic input is believed to remove the inhibitory effect of the interneurons and to allow Portions of this research were presented at the annual meeting of the Society for Psychophysiological Research, Vancouver, Canada, 1996. The research was supported in part by the Committee on Research of the Academic Senate of the Los Angeles Division of the University of California, and by a predoctoral fellowship from the National Institute of Mental Health~MH14584! We thank Maria Nazarin, Halle Jones, and Valerie Gilman for assistance with data collection, and Bill Troyer for technical and software support. Address reprint requests to: Cindy M. Yee-Bradbury, Department of Psychology, University of California, Los Angeles, 405 Hilgard Avenue, Los Angeles, CA 90095-1563, USA. E-mail: yee@psych.ucla. edu. Psychophysiology, 38 ~2001! , 531–539. Cambridge University Press. Printed in the USA. Copyright © 2001 Society for Psychophysiological Research