P50 Suppression Deficits Research Articles

Dynamic brain functional network based on EEG microstate during sensory gating in schizophrenia

Objective. Cognitive impairment is one of the core symptoms of schizophrenia, with an emphasis on dysfunctional information processing. Sensory gating deficits have consistently been reported in schizophrenia, but the underlying physiological mechanism is not well-understood. We report the discovery and characterization of P50 dynamic brain connections based on microstate analysis. Approach. We identify five main microstates associated with the P50 response and the difference between the first and second click presentation (S1-S2-P50) in first-episode schizophrenia (FESZ) patients, ultra-high-risk individuals (UHR) and healthy controls (HCs). We used the signal segments composed of consecutive time points with the same microstate label to construct brain functional networks. Main results. The microstate with a prefrontal extreme location during the response to the S1 of P50 are statistically different in duration, occurrence and coverage among the FESZ, UHR and HC groups. In addition, a microstate with anterior–posterior orientation was found to be associated with S1-S2-P50 and its coverage was found to differ among the FESZ, UHR and HC groups. Source location of microstates showed that activated brain regions were mainly concentrated in the right temporal lobe. Furthermore, the connectivities between brain regions involved in P50 processing of HC were widely different from those of FESZ and UHR. Significance. Our results indicate that P50 suppression deficits in schizophrenia may be due to both aberrant baseline sensory perception and adaptation to repeated stimulus. Our findings provide new insight into the mechanisms of P50 suppression in the early stage of schizophrenia.

Sensorimotor and sensory gating in depression, anxiety, and their comorbidity

Objectives Abnormal attentional and cognitive processes are thought to increase the risk for depression and anxiety. To improve understanding of brain mechanisms of anxiety and depressive disorders and condition of their comorbidity, the study of early attentional processes was provided. Methods Participants were patients with depressive (80 s.), anxiety (69 s.), and comorbid (41 s.) disorders, and healthy volunteers (50 s.). Acoustic startle response (ASR) and P50 component of the auditory event-related potential were recorded. Results In the ASR model decreased startle response amplitude at the left eye in patients with comorbid disorder was found, and ASR latency was lengthened in all clinical groups. Deficit of prepulse inhibition was unique for comorbid disorder, and might be considered as risk of evolution to more serious condition. Reduced prepulse facilitation was revealed in patients with comorbid and anxiety disorders. In P50 suppression paradigm decreased S1 response amplitude was revealed in all clinical groups, P50 latency was prolonged in depressive and comorbid patients, and P50 suppression deficit was observed in depression and anxiety groups. Conclusions The obtained results might be useful for development of integrative neural models of comorbidity of anxiety and depression, and elaboration of diagnostic and therapeutic approaches.

Association of cognitive and P50 suppression deficits in chronic patients with schizophrenia

ObjectiveCognitive deficits are core symptoms of schizophrenia; however, their pathophysiological mechanisms are still unclear. A sensory gating deficit, as reflected by P50 suppression, has been repeatedly shown in schizophrenia patients, which may be associated with cognitive deficits in this disorder. The present study was to examine the relationship between the P50 suppression and cognitive deficits in patients with schizophrenia, which is still under-investigated. MethodWe recruited 38 chronic schizophrenia patients and 32 matched healthy controls, and assessed their cognition with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and P50 suppression with the electroencephalography system. ResultsThe total and its 4 index scores (all p < 0.05) except for the visuospatial/ constructional index of RBANS were significantly lower in patients compared with healthy controls. However, only the language and attention passed Bonferroni corrections. Patients displayed a significantly higher P50 ratio, higher S2 amplitude, and lower S1 amplitude (all p < 0.05) than healthy controls. Interestingly, only in the patients, the S1 amplitude was associated with both language and attention, and the S2 amplitude with both visuospatial/ constructional and language (all p < 0.05), although all of these significances did not pass the Bonferroni corrections. The P50 ratio was not associated with any of the RBANS scores (all p > 0.05). ConclusionsOur results suggest the P50 suppression deficits in Chinese patients with schizophrenia, which may be associated with cognitive impairments of this illness. Moreover, the amplitude of S1 and the amplitude of S2 may be involved in the different cognitive domain deficits in schizophrenia patients. SignificanceThis study suggests that the P50 components may possibly be effective biomarkers for cognitive deficits in patients with schizophrenia.

F34. AUDITORY SENSORY GATING IN YOUNG ADOLESCENTS WITH EARLY-ONSET PSYCHOSIS: A COMPARISON WITH ADHD

BackgroundNumerous studies have demonstrated impaired sensory gating in schizophrenia and this phenomenon has been proposed as a candidate biomarker for the disorder. Sensory gating is typically assessed during an auditory paired-click test commonly referred to as a P50 suppression paradigm. When two identical stimuli are presented, healthy subjects show a decrease in their neural response to the second stimulus, reflected in a decreased P50 amplitude, whereas schizophrenia patients on average show a much smaller decrease. So far, sensory gating has primarily been investigated in adult patients with schizophrenia, but gating disturbances have also been demonstrated in other illnesses, e.g. in schizotypal personality disorder, albeit less marked. Although the typical age of onset for schizophrenia is late adolescence to early adulthood, a sizable group of patients presents with psychotic symptoms during childhood or early adolescence. Manifestation of psychotic symptoms before the age of 18 is commonly referred to as early-onset psychosis (EOP). Various studies have reported a more severe course of illness and a poorer outcome in EOP compared to the adult-onset form of the disorder. In parallel, we expect more pronounced sensory gating deficits in EOP.Impaired sensory gating may not be specific to psychosis, but rather a shared disturbance of neuropsychiatric disorders. Although symptoms of attention deficit hyperactivity disorder (ADHD) differ in many ways from those found in schizophrenia, there are common characteristics. Compared to schizophrenia, relatively few studies have investigated sensory gating in ADHD, and some report P50 gating deficits similar to those frequently found in patients with schizophrenia.MethodsWe investigated P50 suppression in a large cohort of adolescents (12–17 years old) consisting of patients with either EOP (N=56) or ADHD (N=28) as well as age and gender matched healthy controls (N=72). In our paradigm two identical sounds (clicks) were presented separated by a 500ms interval. The amount of suppression was expressed as the ratio between the P50 amplitude of a subject’s response to the first click and his/her amplitude in response to the second click.ResultsThe EOP patients scored significantly higher on PANSS (positive, negative, general, and total PANSS scores) compared to both ADHD patients and healthy controls. However, there were neither significant group differences in raw P50 amplitude, nor in the gating ratios between young adolescents with EOP, ADHD and healthy controls.DiscussionThis is the first study to investigate sensory gating in young adolescents with EOP. We found no P50 suppression deficits in these patients which, given the relatively large sample size in our study, cannot merely be ascribed to power issues. The results are in contrast with the majority of studies investigating sensory gating in schizophrenia and ADHD. However, the results are in agreement with earlier studies from our lab showing evidence of inconsistent P50 suppression deficits in two separate cohorts of adult, antipsychotic naïve, first-episode patients with schizophrenia. Based on our findings, P50 sensory gating cannot differentiate between young adolescents with EOP or ADHD, and deficient P50 suppression does not seem to be a valid biomarker for EOP.

Clinical and Cognitive Significance of Auditory Sensory Processing Deficits in Schizophrenia.

Although patients with schizophrenia exhibit impaired suppression of the P50 event-related brain potential in response to the second of two identical auditory stimuli during a paired-stimulus paradigm, uncertainty remains over whether this deficit in inhibitory gating of auditory sensory processes has relevance for patients' clinical symptoms or cognitive performance. The authors examined associations between P50 suppression deficits and several core features of schizophrenia to address this gap. P50 was recorded from 52 patients with schizophrenia and 41 healthy comparison subjects during a standard auditory paired-stimulus task. Clinical symptoms were assessed with the Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms. The MATRICS Consensus Cognitive Battery was utilized to measure cognitive performance in a subsample of 39 patients. Correlation and regression analyses were conducted to examine P50 suppression in relation to clinical symptom and cognitive performance measures. Schizophrenia patients demonstrated a deficit in P50 suppression when compared with healthy subjects, replicating prior research. Within the patient sample, impaired P50 suppression covaried reliably with greater difficulties in attention, poorer working memory, and reduced processing speed. Impaired suppression of auditory stimuli was associated with core pathological features of schizophrenia, increasing confidence that P50 inhibitory processing can inform the development of interventions that target cognitive impairments in this chronic and debilitating mental illness.

Spectral decomposition of P50 suppression in schizophrenia during concurrent visual processing

Reduced suppression of the auditory P50 event-related potential has long been associated with schizophrenia, but the mechanisms associated with the generation and suppression of the P50 are not well understood. Recent investigations have used spectral decomposition of the electroencephalograph (EEG) signal to gain additional insight into the ongoing electrophysiological activity that may be reflected by the P50 suppression deficit. The present investigation extended this line of study by examining how both a traditional measure of sensory gating and the ongoing EEG from which it is extracted might be modified by the presence of concurrent visual stimulation — perhaps better characterizing gating deficits as they occur in a real-world, complex sensory environment. The EEG was obtained from 18 patients with schizophrenia and 17 healthy control subjects during the P50 suppression paradigm and while identical auditory paired-stimuli were presented concurrently with affectively neutral pictures. Consistent with prior research, schizophrenia patients differed from healthy subjects in gating of power in the theta range; theta activity also was modulated by visual stimulation. In addition, schizophrenia patients showed intact gating but overall increased power in the gamma range, consistent with a model of NMDA receptor dysfunction in the disorder. These results are in line with a model of schizophrenia in which impairments in neural synchrony are related to sensory demands and the processing of multimodal information.

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.

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.

Attentional modulation of the P50 suppression deficit in recent-onset and chronic schizophrenia.

Schizophrenia is associated with deficits in P50 suppression to the second stimulus in a pair, a process often conceptualized as a preattentive index of sensory gating. This study assessed the malleability of the deficit by determining whether early attentional control can influence P50 gating across different phases of schizophrenia. Participants included 28 patients in the recent-onset (n = 16) or chronic (n = 12) phase of illness and 28 healthy comparison subjects. During the standard paradigm, chronic schizophrenia patients exhibited impaired P50 suppression relative to healthy subjects, whereas recent-onset schizophrenia patients were intermediate. Directing voluntary attention toward the initial stimulus yielded substantial improvements in the P50 ratio; recent-onset schizophrenia patients achieved ratio scores comparable to those of healthy participants, whereas chronic patients also improved and could no longer be distinguished clearly from the healthy comparison sample. Directing attention toward the second stimulus enhanced P50 amplitude to the second stimulus across groups, possibly because activation of the inhibitory mechanism was overridden or circumvented by task demands. Thus, P50 suppression may be primarily preattentive under standard conditions, but manipulation of early attention can exert a modulatory influence on P50, indicating that the suppression deficit is malleable in schizophrenia without pharmacological agents.

P50 sensory gating is related to performance on select tasks of cognitive inhibition

P50 suppression deficits have been documented in clinical and nonclinical populations, but the behavioral correlates of impaired auditory sensory gating remain poorly understood. In the present study, we examined the relationship between P50 gating and healthy adults' performance on cognitive inhibition tasks. On the basis of load theory (Lavie, Hirst, de Fockert, & Viding, 2004), we predicted that a high perceptual load, a possible consequence of poor auditory P50 sensory gating, would have differential (i.e., positive vs. negative) effects on performance of cognitive inhibition tasks. A dissociation was observed such that P50 gating was negatively related to interference resolution on a Stroop task and positively related to response inhibition on a go/no-go task. Our findings support the idea that a high perceptual load may be beneficial to Stroop performance because of the reduced processing of distractors but detrimental to performance on the go/no-go task because of interference with stimulus discrimination.

Alterations of Auditory P50 Suppression in Human Fear Conditioning and Extinction

Auditory P50 suppression, assessed by using a paired auditory stimulus (S1 and S2) paradigm to record P50 mid-latency evoked potential, is assumed to reflect sensory gating. Recently, P50 suppression deficits were found in patients with anxiety disorders, including panic disorder, obsessive compulsive disorder, and posttraumatic stress disorder. The processes of fear conditioning are thought to play roles in pathophysiology of anxiety disorders. Our aim was to investigate whether sensory gating would be physiologically altered by fear conditioning. To clarify the relationship between classical fear conditioning and the sensory gating mechanism, we measured changes of P50 and N100 suppression of 21 healthy volunteers in control (baseline) phase, in fear acquisition phase, and in fear extinction phase. The mean P50 S2/S1 ratio in fear acquisition phase was significantly elevated in comparison with that in control phase, and it recovered into basal level in extinction phase. In contrast, the mean N100 S2/S1 ratio showed no changes through all phases from fear acquisition to extinction. These results suggest that the P50 but not N100 sensory gating mechanism might be physiologically associated with fear acquisition and extinction.

Further evidence for shared genetic effects between psychotic bipolar disorder and P50 suppression: A combined twin and family study

P50 suppression deficit has been reported in patients with psychotic bipolar disorder. In our previous report on twin pairs concordant and discordant for bipolar disorder, we found significant genetic overlap between bipolar disorder and P50 sensory gating. However, the sample size in that study was relatively small. A separate study, the Maudsley Bipolar Family Study, reported diminished P50 gating in unaffected relatives of psychotic bipolar patients. However, genetic and environmental influences are confounded in family studies due to lack of monozygotic (MZ) twin pairs. The current study combines the twin sample and the family sample in order to improve statistical power and study design, with the aims of: (1) substantiating the association between psychotic bipolar disorder and diminished P50 suppression and (2) verifying the genetic overlap between the two traits reported in the twin sample. We also assessed the relationship between bipolar disorder and an alternative suppression index, the P50 Condition-Testing (C-T) amplitude difference. A total of 309 subjects was included in this study, comprising 91 twin pairs, 31 bipolar families, and 45 unrelated healthy controls. Statistical analyses were based on structural equation modeling. Bipolar disorder was significantly associated with a diminished P50 suppression ratio and decreased C-T amplitude difference. Shared genetic factors were the main source of these associations. Suppression impairment was due to larger, poorly gated, T amplitude responses. The results provide further evidence that impaired P50 suppressions are promising endophenotypes for psychotic bipolar disorder. The non-specificity of impaired P50 suppression may reflect the impact of shared psychosis susceptibility genes.

Haloperidol Differentially Modulates Prepulse Inhibition and P50 Suppression in Healthy Humans Stratified for Low and High Gating Levels

Schizophrenia patients exhibit deficits in sensory gating as indexed by reduced prepulse inhibition (PPI) and P50 suppression, which have been linked to psychotic symptom formation and cognitive deficits. Although recent evidence suggests that atypical antipsychotics might be superior over typical antipsychotics in reversing PPI and P50 suppression deficits not only in schizophrenia patients, but also in healthy volunteers exhibiting low levels of PPI, the impact of typical antipsychotics on these gating measures is less clear. To explore the impact of the dopamine D2-like receptor system on gating and cognition, the acute effects of haloperidol on PPI, P50 suppression, and cognition were assessed in 26 healthy male volunteers split into subgroups having low vs high PPI or P50 suppression levels using a placebo-controlled within-subject design. Haloperidol failed to increase PPI in subjects exhibiting low levels of PPI, but attenuated PPI in those subjects with high sensorimotor gating levels. Furthermore, haloperidol increased P50 suppression in subjects exhibiting low P50 gating and disrupted P50 suppression in individuals expressing high P50 gating levels. Independently of drug condition, high PPI levels were associated with superior strategy formation and execution times in a subset of cognitive tests. Moreover, haloperidol impaired spatial working memory performance and planning ability. These findings suggest that dopamine D2-like receptors are critically involved in the modulation of P50 suppression in healthy volunteers, and to a lesser extent also in PPI among subjects expressing high sensorimotor gating levels. Furthermore, the results suggest a relation between sensorimotor gating and working memory performance.

Noradrenergic antagonism of the P13 and N40 components of the rat auditory evoked potential

Two rat auditory evoked potential (AEP) components P13 and N40 are suggested as analogues to the human P50, which has abnormal suppression properties in schizophrenia. However, P50 likely reflects neural activity from several different brain areas. Studies examining each of these components in the rat model have proposed circuitry that involves alpha2 norepinephrine (NE) receptors, and different disruption effects are predicted depending on whether effects are presynaptic or postsynaptic. The aim of this paper is to test differential effects of NE antagonism on disruption of normal P13 and N40 expression. AEPs were recorded simultaneously in alert, freely moving rats using the alpha2 antagonist yohimbine. Amplitudes of P13 and N40 elicited by 500-ms interstimulus interval click pairs were measured after administration of a placebo and three doses of the yohimbine. A high dose of yohimbine yielded smaller P13 amplitudes to both clicks, consistent with presynaptic action. However, a moderate yohimbine dose yielded increased P13 amplitudes to both clicks. For N40, a moderate dose of yohimbine yielded increased amplitudes to the second stimulus, and a high dose restored normal suppression, which is consistent with previously reported findings. This study demonstrated that noradrenergic activity differentially affects P13 and N40 components. As P13 and N40 are each models of human P50, these findings highlight the complex circuitry that likely underlies P50. An appreciation for these complexities is critical for understanding the mechanisms of the P50 suppression deficit in schizophrenia, which may be influenced by both trait and state factors.

Failure to Find P50 Suppression Deficits in Young First-Episode Patients With Schizophrenia and Clinically Unaffected Siblings

To evaluate whether the P50 gating deficit is present in young first-episode patients with schizophrenia and their healthy young siblings. An auditory paired-click paradigm was used to assess P50 gating in 53 patients, 27 unaffected siblings, and 28 healthy controls. P50 parameters were compared between patients, sibs, and unrelated controls by a mixed-effects regression model. P50 gating was not significantly impaired in patients with schizophrenia and healthy siblings as compared with controls. P50 gating was not found to be significantly impaired in young first-episode schizophrenia patients and in healthy young siblings. These results are in contrast with the existing literature. We suggest that P50 gating impairment may be developmentally or age dependent.

The Adenosine Antagonist Theophylline Impairs P50 Auditory Sensory Gating in Normal Subjects

In the P50 suppression paradigm, when two auditory stimuli are presented 500 ms apart, the amplitude of the second response (S2), compared with the first (S1), is markedly attenuated in healthy subjects. This is an index of sensory gating. Most schizophrenic patients fail to inhibit the P50 response to the second stimulus, which is assumed to reflect an inhibitory deficit. Adenosine is a neuromodulator with mostly inhibitory activity which is released by physiological stimuli. Since this inhibitory pattern resembles the phenomenon of sensory gating, the contribution of adenosine to P50 suppression was investigated in normal volunteers after treatment with the adenosine antagonist theophylline or placebo. P50 recordings were conducted in thirteen healthy subjects at baseline and 5, 30, 60, and 90 min after oral administration of theophylline (0.66 mg/kg, maximum dose of 500 mg) or placebo in a cross-over design. Baseline results from 17 drug-treated schizophrenic patients were included for comparison. Compared with placebo, theophylline treatment significantly increased P50 ratio (S2/S1) from 0.28 ± 0.03 to 0.82 ± 0.11 at 30 min and 0.61 ± 0.07 at 60 min (mean ± SEM), which were not significantly different from the schizophrenia group (0.74 ± 0.05). The increased P50 ratio by theophylline was due to a combined decrease in S1 and increase in S2 amplitude. The impairment of P50 suppression by theophylline in normal subjects suggests a modulatory role of adenosine in sensory gating, which may be related to P50 suppression deficit in schizophrenia and is in agreement with a hypoadenosinergic model of schizophrenia.

Associations of P50 suppression and desensitization with perceptual and cognitive features of “unreality” in schizotypy

Background: P50 suppression is an electrophysiologic index of early sensory gating and has consistently been found deficient in schizophrenic patients. This gating deficit is thought to lead to sensory overload and cognitive fragmentation, and correspondingly many symptoms of the disorder. However, the link between P50 suppression deficits and symptomatology is yet to be established, and so this study was designed to determine whether such a relation is present within a nonclinical population. Methods: P50 suppression and schizotypy measures were obtained from 36 healthy volunteers, and correlation analyses determined whether measures of schizotypy were related to P50 suppression. Results: Consistent with the view that P50 gating deficits are related to schizophrenic symptoms, subjects with poorer P50 suppression reported more perceptual anomalies and magical ideation—an unreality syndrome—in contrast to other positive symptoms and to withdrawal. This study also found a trend to P50 suppression desensitization, and that whereas subjects low on “unreality” demonstrated desensitization to the second of the paired clicks, subjects high on “unreality” demonstrated sensitization. Conclusions: It is concluded that early sensory gating deficits, in the form of poor P50 suppression, are related to unreality aspects of schizotypy. This supports the view that poor P50 suppression in schizophrenia is related to symptomatology.

Amphetamine disrupts P50 suppression in normal subjects

Background: P50 suppression is viewed as an operational measure of sensory “gating” that is reduced in patients with schizophrenia and their family members. Previous reports have demonstrated that neural gating is regulated by monoaminergic tone in rodent models of P50 suppression. Methods: In this study, 11 healthy subjects participated in P50 event-related potential recordings at baseline and after either oral administration of dextroamphetamine (.3 mg/kg) or placebo, to determine if the administration of a monoaminergic agonist produces P50 suppression deficits similar to those observed in patients with schizophrenia. Results: As hypothesized, amphetamine disrupted the suppression of the P50 event-related potential. There was a statistically significant decrement in P50 suppression during the amphetamine challenge condition ( t 10 = 3.15, p < .01, mean difference = −44.1%, d = −2.5) relative to the baseline P50 condition. A comparison of P50 suppression in the placebo and amphetamine conditions (both after a baseline recording session) revealed a significant amphetamine-induced disruption of P50 suppression ( t 6 = 3.71, p < .01, mean difference = −54.4%, d = −3.14). Conclusions: The biochemical alterations associated with an amphetamine-induced disruption of P50 suppression in this study may be related to the pathophysiology of P50 suppression deficits in schizophrenia. The findings are consistent with several careful examinations of suppression deficits in rodent models that have identified the monoaminergic regulation of P50 suppression. These data indicate that amphetamine induces a disruption of P50 suppression in normal subjects.

Human and animal studies of schizophrenia-related gating deficits.

Prepulse Inhibition (PPI) of the startle response and the P50 auditory-evoked potential suppression are used to assess impairments in the regulation of the neural substrates and to determine the clinical significance of inhibitory deficits in schizophrenia. The study of gating deficits in schizophrenia and in related animal model studies have already advanced our understanding of the neural substrates of information processing abnormalities in patients with schizophrenia. Individuals with schizotypal personality disorder as well as clinically unaffected family members of patients with schizophrenia show PPI and P50 suppression deficits. These "schizophrenic spectrum" populations are not grossly psychotic, nor are they receiving antipsychotic medications. Therefore, the gating deficits are presumed to reflect core (eg, intermediate phenotypic) schizophrenia-linked information processing abnormalities. Several studies have reported that gating deficits are associated with clinical ratings of psychiatric symptoms, thought disorder, and neuropsychologic deficits in patients with schizophrenia. In addition, recent human pharmacologic studies have indicated that gating deficits can be reversed by rationally-selected compounds. Animal model studies have generally shown convergence with the human studies and may lead to improved identification of efficacious new antipsychotic medications for patients with schizophrenia.

Multiple site evaluation of P50 suppression among schizophrenia and normal comparison subjects

Normally, when two brief, non-startling auditory stimuli are presented 500 ms apart, with long (e.g., 10 s) interpair intervals, the positive potential occurring approx. 50 ms after the first stimulus (P50) is relatively large, and the P50 to the second stimulus is smaller. In schizophrenia patients, however, the P50 to the second stimulus is larger than normal. In this study, 36 schizophrenia and 36 normal comparison subjects were tested in a two-click paradigm. Data were recorded from six electrode locations (F3, Fz, F4, C3, Cz, C4). The results support the hypothesis that schizophrenia patients have poor P50 suppression that is not an artifact of differential P50 wave morphology or differences in the number of usable trials between groups. In addition, the vertex location alone (Cz) was equal to, if not better than, any combination of sites for differentiating between groups. These results support the use of the Cz site alone in most investigations of P50 suppression deficits among schizophrenia spectrum patients. Further work investigating the neuropathological correlates of poor P50 suppression among schizophrenia patients by recording from multiple electrode locations, however, could be helpful.