Do schizophrenics' brains respond abnormally to sensory stimuli? Adler, Freedman, and associates, using a stimulus sequence of paired-clicks, claimed that inhibition of a particular early feature of the auditory evoked response (P50) at 500 msec intervals is strong in normal adults but weak or absent in schizophrenic patients. However, this phenomenon has not been replicated in normal subjects, nor has its relation been investigated to the positive wave at the same latency (known variously as P1 or Pb) evoked in many experiments employing much higher repetitive rates of stimulation (1-10/s). Part I of this proposal will comprise three sets of intensive electrophysiological experiments using multiple scalp electrodes on a small group of normal adult subjects. In each experiment adequate numbers of responses will be recorded to explore within- and across-subject variability, as well as measurement of the topographic distribution and temporal stability of the phenomena observed. Part I will first explore the relation of the auditory P50 wave recorded using stimulus rates of 1 per 10 sec to the positive wave(s) near 50 msecs referred to by others as P1 of the Late Wave Sequence (using rates near 1/s), or Pb of the Middle Latency Sequence (rates near 10/s). Second, it will investigate the timecourse of P50 inhibition using a set of paired-click experiments similar to those of Adler and Freedman, et al. but with varying inter- and intra-pair intervals. Third, it will compare the timecourse of P50 inhibition to the timecourse of perturbation (inhibition, augmentation, phase shift) of the 40 Hz steady-state response following paired-dropouts in a 40 Hz auditory click probe train, as in the recent experiments of Makeig on the """"""""40 Hz CERP."""""""" Part II will compare the P50 and/or CERP inhibition measured in a small pilot group of adult schizophrenics with that of the normal subjects in Part I. Selection of experimental parameters in Part II will depend upon the results of Part I.
