P50 Suppression Research Articles

P50 suppression in human discrimination fear conditioning paradigm using danger and safety signals

Auditory P50 suppression, which is assessed using a paired auditory stimuli (S1 and S2) paradigm to record the P50 mid-latency evoked potential, is assumed to reflect sensory gating. Recently, P50 suppression deficits were observed in patients with anxiety disorders, including panic disorder, post-traumatic stress disorder and obsessive–compulsive disorder, as we previously reported. The processes of fear conditioning are thought to play a role in the pathophysiology of anxiety disorders. In addition, we found that the P50 sensory gating mechanism might be physiologically associated with fear conditioning and extinction in a simple human fear-conditioning paradigm that involved a light signal as a conditioned stimulus (CS+). Our objective was to investigate the different patterns of P50 suppression in a discrimination fear-conditioning paradigm with both a CS+ (danger signal) and a CS− (safety signal). Twenty healthy volunteers were recruited. We measured the auditory P50 suppression in the control (baseline) phase, in the fear-acquisition phase, and in the fear-extinction phase using a discrimination fear-conditioning paradigm. Two-way (CSs vs. phase) Analysis of variance with repeated measures demonstrated a significant interaction between the two factors. Post-hoc LSD analysis indicated that the P50 S2/S1 ratio in the CS+ acquisition phase was significantly higher than that in the CS− acquisition phase. These results suggest that the auditory P50 sensory gating might differ according to the cognition of the properties (potentially dangerous or safe) of the perceived signal.

Association Analysis of 94 Candidate Genes and Schizophrenia-Related Endophenotypes

While it is clear that schizophrenia is highly heritable, the genetic basis of this heritability is complex. Human genetic, brain imaging, and model organism studies have met with only modest gains. A complementary research tactic is to evaluate the genetic substrates of quantitative endophenotypes with demonstrated deficits in schizophrenia patients. We used an Illumina custom 1,536-SNP array to interrogate 94 functionally relevant candidate genes for schizophrenia and evaluate association with both the qualitative diagnosis of schizophrenia and quantitative endophenotypes for schizophrenia. Subjects included 219 schizophrenia patients and normal comparison subjects of European ancestry and 76 schizophrenia patients and normal comparison subjects of African ancestry, all ascertained by the UCSD Schizophrenia Research Program. Six neurophysiological and neurocognitive endophenotype test paradigms were assessed: prepulse inhibition (PPI), P50 suppression, the antisaccade oculomotor task, the Letter-Number Span Test, the California Verbal Learning Test-II, and the Wisconsin Card Sorting Test-64 Card Version. These endophenotype test paradigms yielded six primary endophenotypes with prior evidence of heritability and demonstrated schizophrenia-related impairments, as well as eight secondary measures investigated as candidate endophenotypes. Schizophrenia patients showed significant deficits on ten of the endophenotypic measures, replicating prior studies and facilitating genetic analyses of these phenotypes. A total of 38 genes were found to be associated with at least one endophenotypic measure or schizophrenia with an empirical p-value<0.01. Many of these genes have been shown to interact on a molecular level, and eleven genes displayed evidence for pleiotropy, revealing associations with three or more endophenotypic measures. Among these genes were ERBB4 and NRG1, providing further support for a role of these genes in schizophrenia susceptibility. The observation of extensive pleiotropy for some genes and singular associations for others in our data may suggest both converging and independent genetic (and neural) pathways mediating schizophrenia risk and pathogenesis.

Reduced prepulse inhibition as an early vulnerability marker of the psychosis prodrome in adolescence

BackgroundThe onset of psychosis is thought to be preceded by neurodevelopmental changes in the brain. However, the timing and nature of these changes have not been established. The aim of the present study was to determine whether three “classic” neurophysiological markers of schizophrenia are also characteristic of young adolescents (12–18years) at ultra-high risk for psychosis (UHR). Methods63 young UHR individuals and 68 typically developing, age-, sex- and IQ-matched controls were recruited for neurophysiological assessment. Data for P50 suppression, prepulse inhibition (PPI) and smooth pursuit eye movements (SPEM) were gathered and compared. ResultsUHR individuals showed reduced PPI compared to controls, which became more pronounced when controls were directly compared to medication-naive UHR individuals (N=39). There were no group differences in P50 or SPEM measures. ConclusionsThese results suggest that PPI is a relatively early vulnerability marker, while changes in other neurophysiological measures may only be detected or affected later during the illness course. Antipsychotic and antidepressant medication may aid in elevating PPI levels and potentially have a neuroprotective effect.

The effects of sertindole on sensory gating, sensorimotor gating, and cognition in healthy volunteers

Sensory gating, indexed by P50 suppression, and sensorimotor gating, indexed by prepulse inhibition (PPI), are impaired in schizophrenia spectrum disorders. There is considerable evidence that schizophrenia patients treated with atypical antipsychotics exhibit relatively less gating deficits than do other patients with schizophrenia. Some recent studies have investigated the effects of antipsychotic medications on gating in healthy volunteers exhibiting low levels of gating, rather than in patients. Therefore, the current study investigated the influence of sertindole versus placebo in two separate experimental sessions, on PPI, P50 suppression, and cognition in 30 male volunteers stratified for low and high baseline gating levels. Sertindole increased PPI and P50 suppression in healthy subjects exhibiting low baseline PPI and low baseline P50 suppression, respectively, while sertindole attenuated gating in subjects exhibiting high baseline gating. Furthermore, subjects exhibiting low PPI chose worse strategies in a spatial working memory task. These findings suggest that mixed D(2)/5-HT(2) receptor antagonists enhance both PPI and P50 suppression in a way that enhances it in healthy subjects exhibiting low baseline gating. Furthermore, the results militate in favor of the concomitant assessment of PPI, P50 suppression and cognitive measures while investigating the effect of antipsychotic medication in healthy subjects.

Neuromagnetic oscillations and hemodynamic correlates of P50 suppression in schizophrenia

Behavioral and electrophysiological data indicate compromised stimulus suppression in schizophrenia. The physiological basis of this effect and its contributions to the etiology of the disease are poorly understood. We examined neural and metabolic measures of P50 suppression in 12 patients with schizophrenia and controls. First, whole-head magnetoencephalography (MEG) assessed amplitudes of left- and right-hemispheric evoked responses and induced oscillations. Secondly, functional magnetic resonance imaging (fMRI) measured the hemodynamic responses to pairs of beeps with a short interval (500 ms) as compared with those with a long interval (1500 ms). The suppression of alpha power (8–13 Hz) time-locked to the stimuli was negatively correlated with the suppression of evoked components and the hemodynamic measures. Remarkably, the suppression of alpha power was reduced in the patients already prior to stimulus onset. Conceivably, alpha oscillations play a central role in stimulus adaptation of neuronal networks and reflect an active mechanism for sensory suppression. The reduced stimulus suppression in schizophrenia seems to be in part due to impaired generation of alpha oscillations in the auditory cortex, resulting in higher metabolic demand as detected by fMRI. Delayed recovery of alpha rhythm may reflect an impaired gating function and contribute to sensory and cognitive deficits in schizophrenia.

Pattern of P50 suppression deficit in patients with epilepsy and individuals with schizophrenia

To identify P50 suppression in patients with epilepsy, to investigate the effect of seizure control on P50 suppression, and to compare epilepsy patients with individuals with schizophrenia and healthy volunteers. P50 evoked potential parameters and P50 suppression were studied crossectionally in patients with uncontrolled or controlled epilepsy, in individuals with schizophrenia and in healthy volunteers. Individuals with schizophrenia had significantly smaller conditioning stimulus (S1) amplitude, and patients with epilepsy had larger test stimulus (S2) amplitude. Mean S2/S1 ratio was 0.71 ± 0.33 for patients with uncontrolled epilepsy; 0.68 ± 0.36 for patients with controlled epilepsy; 0.96 ± 0.47 for individuals with schizophrenia, and 0.42 ± 0.24 for healthy volunteers. The sensory filter of patients with epilepsy is altered, and this alteration is not associated with seizure control. Also, it works differently from the sensory filter of individuals with schizophrenia.

Psychophysiological Markers of Vulnerability to Psychopathology in Men with an Extra X Chromosome (XXY)

Studying genetically defined syndromes associated with increased risk for psychopathology may help in understanding neurodevelopmental mechanisms related to risk for psychopathology. Klinefelter syndrome (47,XXY) is one of the most common sex chromosomal aneuploidies (1 in 650 male births) and associated with increased vulnerability for psychopathology, including psychotic symptoms. Yet, it remains unknown whether this increased risk is associated with underlying psychophysiological mechanisms that are typically deficient in individuals with psychotic disorders. The present study assessed three “classic” psychophysiological markers of psychosis in Klinefelter syndrome (KS): smooth pursuit eye movements (SPEM), prepulse inhibition (PPI) and P50 suppression. Fourteen adults with KS and 15 non-clinical adults participated in the study. Data on SPEM (reflecting visuo-motor control) as well as PPI and P50 suppression (reflecting sensory gating) were collected. Dysfunctions in SPEM were observed in individuals with KS, with less smooth pursuit as expressed in lower position gain. Also, reduced sensory gating in individuals with KS was suggested by significantly reduced prepulse inhibition of the startle response (PPI) (effect size 1.6). No abnormalities were found in suppression of the P50 (effect size 0.6). We speculate that impairments in these psychophysiological mechanisms may reflect core brain dysfunctions that may also mediate the described increased vulnerability for psychotic symptoms in KS. Although speculative, such deficit specific, rather than disorder specific, psychophysiological dysfunctions in KS might convey vulnerability to other types of psychopathology as well. As KS already can be diagnosed prenatally, the predictive value of childhood impairments in prepulse inhibition and smooth pursuit for development of psychopathology later in life could be assessed. In sum, studying individuals with KS may prove to be an avenue of research leading to new hypotheses and insights into “at risk” pathways to psychopathology.

Sensory gating, inhibition control and child intelligence: an event-related potentials study

The current study explored the relationship among sensory gating, inhibition control and human intelligence in two groups of children with different intellectual levels. A Go-Nogo task was adopted to investigate children's behavioral performances in inhibition control processing, and a paired-click paradigm with event-related potentials (ERP) recording was used to explore children's neural activation during sensory gating processing. The behavioral results showed that the intellectually gifted children committed significantly less commission error rate, which indicated that gifted children had better inhibition control than their average peers. The electrophysiological results showed that the gifted group had lower S2P50/S1P50 amplitude ratio than the average group and illustrated that gifted children had stronger sensory gating. The results of correlation analysis between inhibition control performances and sensory gating showed that children with stronger P50 suppression (lower S2/S1 latency ratio) in the fronto-central area and stronger N100 suppression (lower S2/S1 amplitude ratio) in the frontal and fronto-central areas had shorter reaction time in the Go-Nogo task. Moreover, the correlation patterns between sensory gating and inhibition control were different between two groups of children. The present findings further demonstrated the close relationship among sensory gating, inhibition control and human intelligence in children.

P01-418 - The influence of deviant behavior on inhibitory gating measures in schizophrenic patients

Schizophrenia patients exhibit inhibitory gating deficit in the prepulse inhibition (PPI) of acoustic startle response (ASR) and in the P50 auditory evoked potential suppression.Deviant sexual behavior (DSB) often complicates early clinical identifying of schizophrenic disorder. In this study we assessed the inhibitory gating measures in schizophrenic patients with DSB.Participants (males) were 12 schizophrenic patients with DSB, 14 schizophrenic controls (SC) and 26 healthy controls (HC). DSB was mainly related to disorders of sexual preference. P50 suppression was measured during two runs of 50 click pairs with 500-msec interval. PPI was measured using a series of prepulse-pulse pairs with lead intervals (LI) 60 ms and 120 ms.SC group showed reduced PPI compared to HC. PPI deficit was the most prominent at 60 ms LI, and was right-sided only at 120-ms LI. DSB group demonstrated left-sided reduced PPI at 60 ms LI and left eye ASR latency reduction at 120 ms LI. SC exhibited the highest (0,87), and HC the lowest (0,39) S2/S1 ratio in P50 paradigm; the intermediate value (0,67) was found in DSB patients. In both patient groups S2/S1 ratio significantly (p &lt; 0,001) differed from that in HC. No significant differences were revealed in P50 and PPI measures between patient groups that may be related to high variability in SC group.Left-side PPI deficit in DSB patients is possibly related to right hemisphere disturbances that are inherent to patients with sexual disorders. P50 and PPI measures may be useful to identify schizophrenic disorder in patients with DSB.

Differential sensory gating functions between smokers and non-smokers among drug-naive first episode schizophrenic patients

Although an acute effect of cigarette smoking and nicotine on sensory gating of schizophrenias has been investigated in published papers, the chronic effect of cigarette smoking on this phenomenon has not yet been reported. We report the effects of chronic cigarette smoking, without new acute exposure before testing, on sensory gating using the P50 auditory evoked potential in a group of drug-naive first episode schizophrenic smokers and healthy smokers. Sensory gating was evaluated using auditory P50 suppression elicited using the conditioning (S1)–testing (S2) paradigm. Fifty six male drug-naive first episode schizophrenic patients were compared to 41 healthy male controls. Patients were classified into subgroups of current smokers (n=18) and non-smokers (n=38) to explore the effects of smoking on sensory gating. All subjects did not smoke a cigarette for at least 1h prior to testing. Schizophrenic patients showed an increased S2 amplitude and a poorer sensory gating as measured by both S2/S1 ratio and S1–S2 difference of P50 amplitude, as compared to healthy controls. However, smokers showed an increased S1 amplitude and better sensory gating than did non-smokers both in schizophrenia patients and healthy controls. Our findings support a sensory gating deficit among first episode schizophrenic patients. However, it was less pronounced among schizophrenic patients who were current cigarette smokers, suggesting a positive effect of chronic cigarette smoking on ameliorating this sensory gating deficit in schizophrenia. Our findings of the present study present new evidence supporting the self-medication hypothesis of self-medication by cigarette smoking in schizophrenia to possibly ameliorate pre-existing functional deficits.

Source localization of sensory gating: A combined EEG and fMRI study in healthy volunteers

Reduced sensory gating appears to be among the core features in schizophrenia. The sources of sensory gating however are largely unknown. The aim of the current study was to identify these sources, with concurrent EEG and fMRI methodology. Twenty healthy male volunteers were tested with identical P50 suppression paradigms in two separate sessions: an EEG setting, and an EEG concurrent with fMRI setting. The stimuli in the P50 paradigm consisted of weak electrical stimulation of the left median nerve. The stimuli were presented in pairs with either 500ms or 1000ms interstimulus intervals (ISI). No difference was found between the EEG setting and the concurrent EEG and fMRI setting. P50 suppression was, in both settings, found only in the 500ms trials, not in the 1000ms trials. EEG-dipole modeling resulted in 4 sources located in the medial frontal gyrus, the insula, the hippocampus, and primary somatosensory cortex. These sources corresponded to significant fMRI clusters located in the medial frontal gyrus, the insula, the claustrum, and the hippocampus. Activity in the hippocampus and the claustrum was higher in the trials with suppression, suggesting that these brain areas are involved in the inhibitory processes of P50 suppression. The opposite was found for activity in the medial frontal gyrus and the insula, suggesting that these brain areas are involved in the generation of the P50 amplitude. To our knowledge, this is the first study demonstrating that P50 suppression can be reliably assessed inside an MRI scanner.

A single high dose of escitalopram disrupts sensory gating and habituation, but not sensorimotor gating in healthy volunteers

Early mechanisms to limit the input of sensory information to higher brain areas are important for a healthy individual. In previous studies, we found that a low dose of 10mg escitalopram (SSRI) disrupts habituation, without affecting sensory and sensorimotor gating in healthy volunteers. In the current study a higher dose of 15mg was used. The hypothesis was that this higher dose of escitalopram would not only disrupt habituation, but also sensory and sensorimotor gating. Twenty healthy male volunteers received either placebo or 15mg escitalopram, after which they were tested in a P50 suppression, and a habituation and prepulse inhibition (PPI) of the startle reflex paradigm. Escitalopram significantly decreased P50 suppression and habituation, but had no effect on PPI. The results indicate that habituation and sensory gating are disrupted by increased serotonergic activity, while sensorimotor gating seems relatively insensitive to such a rise. Since the patients who are frequently treated with SSRIs (patients with schizophrenia and affective disorders) might already suffer from disrupted sensory gating and habituation, the current results call for caution in the determination of a proper dose.

How human electrophysiology informs psychopharmacology: from bottom-up driven processing to top-down control.

This review surveys human event-related brain potential (ERP) and event-related magnetic field (ERF) approaches to psychopharmacology and psychopathology, and the way in which they complement behavioral studies and other neuroimaging modalities. The major paradigms involving ERP/ERF are P50 suppression, loudness-dependent auditory evoked potential (LDAEP), mismatch negativity (MMN), P300, mental chronometry, inhibitory control, and conflict processing (eg, error-related negativity (ERN)). Together these paradigms cover a range of more bottom-up driven to more top-down controlled processes. A number of relationships between the major neurotransmitter systems and electrocortical mechanisms are highlighted. These include the role of dopamine in conflict processing, and perceptual processing vs motor preparation; the role of serotonin in P50 suppression, LDAEP, and MMN; glutamate/NMDA and MMN; and the role of acetylcholine in P300 generation and memory-related processes. A preliminary taxonomy for these relationships is provided, which should be helpful in attuning possible new treatments or new applications of existing treatments to various disorders.

P17-3 Evaluating event-related potential P50 suppression for diagnostic biomaker for psychiatric disorders

P17-3 Evaluating event-related potential P50 suppression for diagnostic biomaker for psychiatric disorders

An evaluation of P50 suppression methodologies

P50 suppression', an index of sensory gating, has demonstrated utility in schizophrenia research. It is widely reported that P50 suppression is deficient in schizophrenia patients and an endophenotypic marker for the disorder. However, unresolved methodological issues including the unestablished reliability of the measure, unknown effects of time-on-task and long protocol undermine its usefulness. In order to address these methodological issues, twenty healthy participants' P50 suppression was measured in a long P50 paradigm. This enabled the measurement of within-session reliability, temporal course of P50 suppression, and effects of the inter-pair interval parameter. Results indicated good within-session reliability for P50 suppression (ICC = .668); changes in P50 suppression across the session (a 31% increase over the 78 minute recording); and comparable P50 suppression at long (9 s) and short (3 s) inter-pair intervals. It is concluded that given appropriate conditions, P50 suppression can be measured reliably within-session. Further, time-on-task effects need to be taken into account when measuring P50 suppression in a long paradigm or calculating reliability. Lastly, the inter-pair interval can be substantially shortened in studies with healthy participants allowing for an appreciable reduction in P50 suppression recording time.

Sensory gating and sensorimotor gating in medication-free obsessive-compulsive disorder patients

Obsessive-compulsive disorder (OCD) is associated with deficits in inhibition mechanisms. This is reflected in reports showing impaired sensorimotor and sensory gating in OCD patients, as measured with prepulse inhibition (PPI) of the startle reflex and P50 suppression paradigms. However, most of the patients in these studies used medication and the results were not controlled for menstrual cycle phase in women. In this study PPI and P50 suppression were tested in 25 medication-free OCD patients and 25 healthy controls, using auditory stimuli and controlling for menstrual cycle effects. Subgroups were established, based on clinical variables (e.g. 'washers' and 'checkers'). No impairments in PPI or P50 suppression were found in the OCD group when compared with healthy controls. However, a subgroup of OCD patients ('checkers', n=12) showed increased P50 suppression. It was concluded that sensorimotor and sensory gating is not impaired in drug-free OCD patients, taking into account the menstrual cycle effects in women. These results do not support hypotheses linking deficits in these inhibition paradigms and the pathogenesis of OCD. The finding of an increased P50 suppression in the subgroup of 'checkers' deserves further investigation and underlines the value of studying subgroups of OCD.

Electroencephalography (EEG) and Event‐Related Potentials (ERPs) with Human Participants

Understanding the basic neural processes that underlie complex higher-order cognitive operations and functional domains is a fundamental goal of cognitive neuroscience. Electroencephalography (EEG) is a non-invasive and relatively inexpensive method for assessing neurophysiological function that can be used to achieve this goal. EEG measures the electrical activity of large, synchronously firing populations of neurons in the brain with electrodes placed on the scalp. This unit outlines the basics of setting up an EEG experiment with human participants, including equipment, and a step-by-step guide to applying and preparing an electrode cap. Also included are support protocols for two event-related potential (ERP) paradigms, P50 suppression, and mismatch negativity (MMN), which are measures of early sensory processing. These paradigms can be used to assess the integrity of early sensory processing in normal individuals and clinical populations, such as individuals with schizophrenia.

Impairment of Phosphatidylinositol 3-Kinase Signaling in Schizophrenia: State or Trait?

Back to table of contents Previous article Next article Letter to the EditorFull AccessImpairment of Phosphatidylinositol 3-Kinase Signaling in Schizophrenia: State or Trait?Undine E. Lang, M.D., Ph.D.Undine E. LangSearch for more papers by this author, M.D., Ph.D.Published Online:1 Jun 2010https://doi.org/10.1176/appi.ajp.2010.10010103AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: In their article, published in the April 2010 issue of the Journal, Szabolcs Kéri, M.D., Ph.D., D.Sc., et al. (1) showed that neuregulin 1-dependent activation of phosphatidylinositol 3-kinase signaling was impaired in schizophrenia patients, which was connected to P50-evoked response and thereby influenced sensory gating in patients with first-episode schizophrenia. Phosphatidylinositol 3-kinase and phosphoinositide-dependent protein kinase-1 signaling inhibit glycogen synthase kinase-3β. Our workgroup found increased anxiety behavior in phosphoinositide-dependent protein kinase 1 hypomorphic mice (2) and stress-resistant behavior in glycogen synthase kinase-3β knock-in mice, supporting the role of phosphatidylinositol 3-kinase signaling in anxiety and stress (3). However, Dr. Kéri et al. did not examine the influence of neuroleptic treatment on phosphatidylinositol 3-kinase activity. The highly effective atypical antipsychotics olanzapine and clozapine in contrast to haloperidol have been shown to activate the protein kinase B (AKT) glycogen synthase kinase-3β axis (4). These effects might explain heterogenous findings on the P50-evoked response in schizophrenia patients, which seems to normalize after treatment with clozapine and olanzapine but not after typical drugs (5).Berlin, GermanyThe author reports no financial relationships with commercial interests.References1 Kéri S , Beniczky S , Kelemen O : Suppression of the P50 evoked response and neuregulin 1-induced AKT phosphorylation in first-episode schizophrenia. Am J Psychiatry 2010; 167:444–450 Link, Google Scholar2 Ackermann TF , Hörtnagl H , Wolfer DP , Colacicco G , Sohr R , Lang F , Hellweg R , Lang UE : Phosphatidylinositide dependent kinase deficiency increases anxiety and decreases GABA and serotonin abundance in the amygdala. Cell Physiol Biochem 2008; 22:735–744 Crossref, Medline, Google Scholar3 Ackermann TF , Kempe DS , Lang F , Lang UE : Hyperactivity and enhanced curiosity of mice expressing PKB/SGK-resistant glycogen synthase kinase-3 (GSK–3). Cell Physiol Biochem 2010 (in press) Crossref, Google Scholar4 Aubry JM , Schwald M , Ballmann E , Karege F : Early effects of mood stabilizers on the Akt/GSK-3beta signaling pathway and on cell survival and proliferation. Psychopharmacology 2009; 205:419–429 Crossref, Medline, Google Scholar5 Light GA , Geyer MA , Clementz BA , Cadenhead KS , Braff DL : Normal P50 suppression in schizophrenia patients treated with atypical antipsychotic medications. Am J Psychiatry 2000; 157:767–771 Link, Google Scholar FiguresReferencesCited byDetailsCited ByProgress in Neuro-Psychopharmacology and Biological Psychiatry, Vol. 64Reduced Brain-Derived Neurotrophic Factor Serum Concentrations in Acute Schizophrenic Patients Increase During Antipsychotic TreatmentJournal of Clinical Psychopharmacology, Vol. 31, No. 3 Volume 167Issue 6 June 2010Pages 719-719 Metrics PDF download History Accepted 1 March 2010 Published online 1 June 2010 Published in print 1 June 2010

Assessment of auditory sensory processing in a neurodevelopmental animal model of schizophrenia—Gating of auditory-evoked potentials and prepulse inhibition

The use of translational approaches to validate animal models is needed for the development of treatments that can effectively alleviate cognitive impairments associated with schizophrenia, which are unsuccessfully treated by the current available therapies. Deficits in pre-attentive stages of sensory information processing seen in schizophrenia patients, can be assessed by highly homologues methods in both humans and rodents, evident by the prepulse inhibition (PPI) of the auditory startle response and the P50 (termed P1 here) suppression paradigms. Treatment with the NMDA receptor antagonist PCP on postnatal days 7, 9, and 11 reliably induce cognitive impairments resembling those presented by schizophrenia patients. Here we evaluate the potential of early postnatal PCP (20mg/kg) treatment in Lister Hooded rats to induce post-pubertal deficits in PPI and changes, such as reduced gating, in the P1 suppression paradigm in the EEG. The results indicate that early postnatal PCP treatment to rats leads to a reduction in PPI of the acoustic startle response. Furthermore, treated animals were assessed in the P1 suppression paradigm and produced significant changes in auditory-evoked potentials (AEP), specifically by an increased P1 amplitude and reduced P2 (P200 in humans) gating. However, the treatment neither disrupted normal P1 gating nor reduced N1 (N100 in humans) amplitude, representing two phenomena that are usually found to be disturbed in schizophrenia. In conclusion, the current findings confirm measures of early information processing to show high resemblance between rodents and humans, and indicate that early postnatal PCP-treated rats show deficits in pre-attentional processing, which are distinct from those observed in schizophrenia patients.

Sensory Gating Event–Related Potentials and Oscillations in Schizophrenia Patients and Their Unaffected Relatives

The P50 event-related potential sensory gating deficit, a failure to inhibit responses to repeated stimuli, is a leading endophenotype for schizophrenia (SZ). Both gamma and beta event-related oscillations (EROs) are major contributors to the auditory P50 response. However, the topographic distribution of gamma and beta ERO responses to initial (S1) and repeat (S2) stimuli and the association of these oscillations with P50 sensory gating are not clear. A total of 51 schizophrenic patients, 25 unaffected first-degree relatives, and 34 healthy comparison subjects were tested using a paired-click paradigm. Evoked power of gamma- and beta-band responses using wavelet analyses to S1 and S2 stimuli and gating of EROs and P50 were the main outcome measures. A P50 gating deficit was found in patients (P < .001) and at a trend level in relatives (P = .087). Patients showed widely distributed reductions in gamma and beta EROs to S1 stimuli and S2 stimuli, respectively, and impaired gating in both frequencies. Reduced gamma and beta ERO activity in patients was associated primarily with age of onset. Relatives did not differ significantly from control subjects in either EROs power or gating. Gating of P50, gamma, and beta were not significantly correlated (r = .18-.19, P > .05). These results suggest that ERO deficits in gamma to S1 and beta to S2 stimuli and impaired ERO gating are associated with SZ, but are not related to genetic liability for the illness. The components of information processing assessed by gamma- and beta gating appear to be independent from those mediated by P50 suppression.