Effects of Background and Prepulse Characteristics on Prepulse Inhibition and Facilitation: Implications for Neuropsychiatric Research

Abstract

Both prepulse inhibition (PPI) and prepulse facilitation (PPF) deficits have been reported in schizophrenia patients, but the use of different experimental parameters across laboratories makes direct comparisons of results difficult. We assessed the effects of different parameters on PPI and PPF in normal subjects. Eyeblink startle was measured in 14 healthy male subjects, using 115 dB[A] white noise startle pulses and 86 dB[A] prepulses. Analyses compared the effects of: 1) background noise level (ambient 54 vs. 70 dB[A]) on PPI and PPF, 2) prepulse duration (discrete 20 msec vs. continuous) on PPF, 3) prepulse frequency (1000 Hz vs. white noise) on PPI and PPF, and 4) prepulse interval (2000 vs. 4500 msec) on PPF. Compared to an experimentally delivered 70 dB[A] background, ambient 54 dB[A] background led to significantly more PPI (with discrete white noise prepulses), and more PPF (with continuous prepulses). Continuous and longer (4500 msec) prepulses induced more PPF than did discrete and shorter (2000 msec) prepulses. Paradigmatic differences appear likely to be responsible for divergent findings in studies of PPI and PPF in normal and schizophrenia subjects. The present study should guide investigators in the selection of parameters for assessing PPI and PPF in studies of normal subjects and schizophrenia patients. Attention to the 4 factors of 1) background noise, 2) prepulse duration, 3) frequency, and 4) interval will facilitate comparability of results across different laboratories, especially when using PPI/PPF in schizophrenia research as neural substrate probes, as biomarkers, and as endophenotypes.