Measuring P50 Suppression and Prepulse Inhibition in a Single Recording Session

Two distinct measures have been developed to assess inhibitory “gating” functioning in schizophrenia patients: suppression of the P50 event-related potential and prepulse inhibition of the startle response. P50 suppression and prepulse inhibition are conceptually related, operational measures of gating often used in schizophrenia research to identify deficits in the early stages of information processing. Deficient inhibition in P50 suppression (sensory gating) and prepulse inhibition (sensorimotor gating) are among the most consistent findings of information processing deficits in the schizophrenia literature (for reviews, see references 1 and 2).

The P50 is the positive component of the event-related potential that occurs about 50 msec after an auditory stimulus. The change in P50 amplitude is typically measured as response to click pairs separated by 500 msec. The percentage of the amplitude reduction of the P50 response from the first to the second click is the dependent variable, P50 suppression. Patients with schizophrenia have significantly lower than normal levels of P50 suppression, an operational measure of sensory gating (for reviews, see references 1 and 2).

The human startle reflex is typically assessed by using electromyographic (EMG) recordings of the eye-blink component of the startle reflex in response to sudden and powerful multimodal stimuli, most often acoustic stimuli. When the startling stimulus is preceded by a weak prestimulus (i.e., “prepulse”), the magnitude of the eye-blink response is normally reduced. The percentage of the reduction in the startle reflex is the operational measure of sensorimotor gating known as “prepulse inhibition.” As with P50 suppression, patients with schizophrenia often have low levels of prepulse inhibition (for reviews, see references 1 and 2).

Correlational studies (3, 4) of the relationship between P50 suppression and prepulse inhibition suggest that they are distinct, complementary measures of sensory and sensorimotor inhibition, respectively. In the present study, P50 suppression and prepulse inhibition were recorded during the same session to determine whether measurement of P50 and prepulse inhibition is possible in an integrated session. Next, we sought to determine whether levels of P50 suppression and prepulse inhibition measured in this integrated session would yield results equivalent to those obtained in separate sessions in which similar stimulus characteristics were used.

Method

Twelve healthy subjects underwent integrated P50/prepulse inhibition testing. Seven were men, and five were women, and their mean age was 27.3 years (SD=8.2). Subject recruitment, screening, and exclusion procedures have been described previously (5–9). The subjects were given a description of the study, and written consent was obtained (University of California, San Diego, Institutional Review Board number 990937). Reference samples of normal subjects previously and concurrently tested in our laboratory (6–9) were used to determine whether the values of P50 suppression and prepulse inhibition acquired from the single, integrated gating session were equivalent to those obtained by using separate sessions.

Each participant was seated in a recliner and instructed to sit still with his or her eyes open and to focus on a fixation point. During testing, the subjects were monitored visually and by EEG for signs of sleep or slow wave activity, which prompted the experimenter to intervene. Eye movements were assessed with vertical electro-oculography and rectified EMG recordings. The EMG of startle responses was recorded by using two electrodes over the right orbicularis oculi muscle. The EEG was recorded at the Cz site. Electrode resistances were below 5 kΩ.

The stimulus generation and acquisition equipment have been described previously (5–9). A 60-dB background noise was presented during the 2-minute acclimation period and throughout the session. To enhance comparability with separate-session recordings, the stimulus characteristics were based on our previous studies that identified differences between patients and comparison subjects (5–9). The P50-evoking stimuli consisted of 120 click pairs (89 dB, 1-msec duration, 500-msec interclick interval). EEG filtering, artifact rejection, and P50 identification procedures have been previously described (5, 8, 9). The 30 startle pulse-alone stimuli consisted of 40-msec, 115-dB bursts of white noise, and 30 startle prepulse trials were also used, in which a 20-msec noise burst (75 dB) preceded the startle pulse by 60 msec. The trial types were intermixed throughout the session with 6–10-second intertrial intervals (combined session length=26 minutes). The average magnitudes of the startle responses to the pulse-alone and prepulse trials obtained in the first half, second half, and across the entire session were used. Prepulse inhibition was defined as the percent decrease in startle magnitude in the presence of the prepulse compared to the startle magnitude without the prepulse.

Results

Significant P50 amplitude suppression was observed from the first click (mean=3.3 μV) to the second click (mean=0.9 μV) (t=5.32, df=11, p<0.001), resulting in 67.8% (SD=27.5%) mean suppression. These observed P50 values are comparable to those previously obtained in our laboratory by using similar stimuli with normal subjects: 70.1% mean P50 suppression (SD=22.8%) in one study (9) and 63.6% (SD=44.7%) in another (8).

Significant prepulse inhibition was observed by comparing the pulse-alone trials (mean=86.6 μV) with those including prepulses (mean=32.8 μV) (t=2.39, df=11, p<0.05), resulting in 54.9% (SD=29.1%) prepulse inhibition. Equivalent amounts of prepulse inhibition in tests using the same stimulus characteristics in our laboratory have been published: 55.2% prepulse inhibition (SD=40.9%) in one study (7) and 59.9% (SD=20.9%) in another study (6).

There were no significant correlations between startle measures (magnitude, habituation, prepulse inhibition) and P50 measures (amplitude, percent suppression, latency) in the first block, the second block, or the entire session (in all cases, r²<0.16, df=11, p>0.05). Grand average P50 and startle waveforms are presented in Figure 1.

Discussion

This study confirms that measures of P50 suppression and prepulse inhibition can be obtained from a single, combined recording session. The grand average waveforms (Figure 1) appear to be comparable to those obtained when P50 suppression and prepulse inhibition were measured in separate sessions. The levels of P50 suppression and prepulse inhibition are also similar to those obtained in our laboratory in the past (7, 9) and in subjects concurrently tested (6, 8) with comparable stimuli. The lack of significant correlations between the P50 and startle variables should be interpreted with caution, given the small number of subjects in the present study. Clearly, additional counterbalanced within-subjects studies are needed to determine whether the individual values of P50 suppression and prepulse inhibition obtained in a single session correlate with those obtained in separate sessions in future development of this integrated gating test. This will serve as a prelude to testing schizophrenia patients in an integrated P50/prepulse inhibition session, since collection of temporally “contemporaneous” data in a single test session may offer opportunities to better understand the relationships of schizophrenia deficits across both domains of inhibitory functioning.

Presented at the 55th annual meeting of the Society of Biological Psychiatry, May 11–14, 2000, Chicago. Received July 14, 2000; revision received May 14, 2001; accepted May 23, 2001. From the Department of Psychiatry, University of California, San Diego. Address reprint requests to Dr. Braff, Department of Psychiatry, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0804; [email protected] (e-mail). Supported in part by NIMH grant MH-42228 to Dr. Braff and by a grant from the Department of Veterans Affairs (Mental Illness Research, Education, and Clinical Center, Veterans Integrated Service Network 22). The authors thank Mark Geyer and Neal Swerdlow for their suggestions and Joyce Sprock for assistance in conducting the research.