P300 Amplitude Differences Research Articles

Affective and psychotic symptoms relate to different types of P300 alteration in depressive disorder

Background: Previous findings of P300 alterations in depressive disorder have been controversial. We therefore used multivariate methods to study the relationship between P300 and affective and psychotic symptoms in depressive disorder. Methods: The P300 of 22 psychotropic drug-free depressed out-patients was registered within an auditory oddball paradigm. Affective and psychotic symptoms were evaluated using the depression and psychoticism subscales of SCL-90. The relationship of P300 amplitude and latency with affective and psychotic symptoms was assessed with multiple linear regression analysis and ANOVA. P300 values of the depressed patients were also compared with those of 22 healthy controls. Results: Psychotic symptoms were associated with an overall reduction in P300 amplitude, which was pronounced in the left temporocentral electrode chain (T3, C3, Cz). Psychotic symptoms were also associated with a prolonged P300 latency. Affective symptoms were associated with a relational amplitude reduction at the right temporal scalp sites. There were no statistically significant differences in P300 amplitude or latency between depressed and control-subjects. Limitations: Rather small number of study subjects. The psychotic scores were low in all subjects. Multiple statistical analyses were used, and no specific a priori hypothesis was tested. Conclusions: In depressive disorder, affective and psychotic symptoms are associated with different types of P300 alteration, which may indicate different underlying neurobiological processes.

P300 asymmetry in schizophrenia: a meta-analysis

P300 event-related brain potential (ERP) amplitude is smaller in patients with schizophrenia compared to unaffected controls, but whether left temporal component amplitude is also smaller is debated. The present study employed meta-analytical methods to quantitatively assess previous P300 schizophrenia asymmetry findings. All P300 articles on schizophrenia using an auditory oddball paradigm published before January 2000 were obtained by comprehensive literature searches and cross-referencing for related articles. A total of 19 original articles reporting complete midline electrode data and 11 articles reporting lateral asymmetry electrode data were reviewed, which included different independent conditions that yielded 50 independent data sets. P300 amplitude differences between patients with schizophrenia and control subjects from the midline electrodes yielded effect sizes that differed among recording sites, such that Fz was significantly smaller than Pz, with Cz effect sizes smaller than Pz but larger than Fz. Comparison of P300 amplitude from the lateral data for the T3 and T4 electrodes found no reliable effect size difference when these electrodes were analyzed separately. However, comparison of P300 amplitude effect sizes from the TCP1 was significantly larger than that from the TCP2 when these electrodes were analyzed separately. P300 amplitude is smaller overall in patients with schizophrenia compared to control subjects and differs in its effect size topography across the midline and temporal electrode sites, with the strongest effect sizes obtained for the Pz midline and TCP1 lateral electrodes.

P300 event-related potential amplitude as an endophenotype of alcoholism--evidence from the collaborative study on the genetics of alcoholism.

There is substantial information supporting the role of genetic factors in the susceptibility for alcohol dependence. However, the identification of specific genes that contribute to this predisposition has proven elusive, although several theoretically relevant candidates, e.g. DRD2 or 5-HT(1B), have been considered. The difficulty in identifying specific genes may be related to the clinical heterogeneity of the disorder resulting in a poorly defined phenotype for genetic analysis. An alternative approach to the use of a diagnostic phenotype for identifying alcoholism susceptibility genes may lie in the examination of the neurobiological correlates of the disorder, the so-called endophenotypes. One possible endophenotype of alcohol dependence may be related to the P300 waveform of the event-related brain potential (ERP). Using data obtained from the Collaborative Study on the Genetics of Alcoholism (COGA), a multi-site family-based study, the utility of P300 amplitude as an endophentype was examined. Differences in P300 amplitude were found between alcoholics and nonalcoholics, between unaffected relatives of alcoholics and relatives of controls, as well as between unaffected offspring of alcoholic fathers and offspring of controls. A genetic analysis indicated that attributes of the P(3) ERP waveform are heritable, and a quantitative trait locus analysis found linkage to several chromosomal regions. These data provide significant support for P300 as an endophenotype for alcohol dependence.

Stability of genetic and environmental influences on P300 amplitude: a longitudinal study in adolescent twins.

This study examined the stability of genetic and environmental influences on individual differences in P300 amplitude during adolescence. The P300 component is an event-related brain potential (ERP) that has attracted much attention as a biological marker for disturbed cognitive processing in psychopathology. Understanding the genetics of this biological marker may contribute to understanding the genetics of the associated psychopathologies. In a group of 213 adolescent twin pairs, the P300 component was measured twice, the first time at age 16 and the second time 18 months later. A large part of the variance of the P300 amplitude could be explained by familial factors, with estimates ranging from 30% to 81%. Whether the familial resemblance was due to genetic or shared environmental factors depended on sex. For males, genetic factors explained familial resemblance in P300 amplitude, but for females such resemblance was likely due to shared environmental factors. The phenotypic stability of the P300 amplitude from 16 to 18 years was high in both sexes, and stability could be attributed largely to the same familial factors. There was no evidence that new familial influences emerged at age 18.

ERP Indices of Resource Allocation Difficulties in Mild Head Injury

This study examined the hypothesis that distractibility is a characteristic sequela of mild closed head injury (MHI). The Minnesota Multiphasic Personality Inventory (MMPI-2) was used to study whether comorbid stress-related symptoms are associated with behavioral and electrophysiological indexes of attention. Event-related potentials (ERPs) and performance (reaction time, accuracy) were studied in patients with MHI (n = 20), patients with frontal lesions (n = 14), and healthy controls (n = 20) during a three-tone oddball task. Participants were instructed to detect rare target (2000 Hz) tones, and to withhold responding to equally rare distractor (500 Hz) tones and frequently occurring standard (1000 Hz) tones. All groups distinguished the two classes of deviants as indicated by the larger P3 amplitude to target relative to distractor tones. This indicates that the group with MHI was capable of differential allocation of attentional resources to target and non-target events. However, impaired performance and attenuated ERP amplitudes to both classes of deviants relative to patients with frontal lesions and controls, suggest limited availability, or expenditure of the resources needed for adequate task performance. In the group with MHI, both P3 amplitude and reaction time (RT) were significantly related to subjectively reported distress. The difference in RT disappeared, whereas the P3 amplitude differences between the patient groups remained when adjusting for level of distress.

Correlation between coefficient of variation of choice reaction time and components of event-related potentials (P300): effect of benzodiazepine

We studied the relationship between accuracy in the cognitive process and components of event-related potentials (P300) in 21 young and healthy subjects. Benzodiazepine was used to manipulate the cognitive state of the subjects. We recorded the serial changes in P300, choice reaction time (CRT), and error ratio (ER) before and after oral administration of 0.4 mg of alprazolam. After administration, the coefficient of variation of CRT tended to decrease in nine subjects (group I) and increase in 12 subjects (group II). Prolongation of the P300 latency was observed in all subjects after treatment; however, such change was more predominant in group II than in group I. In group I, there was no error and no significant difference in P300 amplitude before and after administration. In group II, alprazolam significantly reduced P300 amplitude and increased ER. Our results suggest that the accuracy and P300 amplitude were preserved when the central nerve system managed to reduce fluctuations in CRT but P300 amplitude diminished and the error ratio increased following deterioration of these processes.

Absence of visual and auditory P300 reduction in nondepressed male and female alcoholics

Background: The P300 component of the event-related potential has been extensively studied as a possible neurobiological risk marker for the development of alcoholism. Although P300 amplitude reduction has frequently been documented in high-risk children, studies of adult alcoholics are inconsistent. Methods: P300 amplitude from 121 adult alcoholics was compared to 68 controls utilizing event-related potential paradigms from the auditory and visual modalities. All participants were evaluated clinically with psychiatric interviews and administered the MMPI. Results: Male alcoholics did not show a reduction in amplitude in either the auditory or visual modality. Female alcoholics showed reduced P300 amplitude, but only when a comorbid lifetime diagnosis of depression was present. Similar results were found using current depressed mood (Scale 2 from the MMPI). Conclusions: No differences in P300 amplitude were found between alcoholics and controls unless comorbid depression was present. Therefore, P300 amplitude reduction seen in children at high-risk for developing alcoholism seems to represent a neurodevelopmental delay that normalizes by adulthood.

Reduced P300 responses in criminal psychopaths during a visual oddball task

Background: Clinicians have long recognized that psychopaths show deficits in cognitive function, but there have been few experimental studies exploring these deficits. We present here the first in a series of event-related potential (ERP) experiments designed to elucidate and characterize the neural correlates of cognitive processes of psychopaths. Methods: We recorded ERPs from a topographic array from 11 psychopathic and 10 nonpsychopathic prison inmates, assessed with the Hare Psychopathy Checklist–Revised, during performance of a visual oddball task. ERPs to target (25% of trials) and nontarget (75% of trials) visual stimuli were analyzed. Results: Consistent with previous research, there were no group differences in the latency or amplitude of the ERPs for the nontarget stimuli. For nonpsychopaths, the P300 amplitude was larger when elicited by the target stimuli than when elicited by the nontarget stimuli. In contrast, psychopaths failed to show reliable P300 amplitude differences between the target and nontarget conditions. Psychopaths had a smaller amplitude P300 to target stimuli than did nonpsychopaths. In addition, the amplitude of the P300 was less lateralized in psychopaths than in nonpsychopaths. Psychopaths also had a larger centrofrontal negative wave (N550) during the target condition than did nonpsychopaths. Conclusions: The results of this study indicate that there are substantial differences between psychopaths and others in the processing of even simple cognitive tasks and provide support for information processing models of psychopathy.

Event-related potentials in schizophrenic patients during a degraded stimulus version of the visual continuous performance task

Previous studies of the auditory P300 event-related potential (ERP) have reported smaller amplitudes in chronic schizophrenics but similar consistencies have not been observed with visual P300s. This study examined P300s in symptomatically stable, medicated, chronic schizophrenics ( n=14) and normal controls ( n=14) performing a visual continuous performance task utilizing degraded stimuli to burden encoding processes. Performance analysis found slower response times, fewer target detections and more false alarms in patients than in controls. Analysis of ERPs showed P300 amplitudes of schizophrenics to be significantly smaller than those of controls and, unlike controls, schizophrenics failed to exhibit significant target vs. non-target P300 amplitude differences. Discriminant analysis indicated target and non-target midline ( F Z, C Z, P Z) P300 amplitudes together correctly classified all patients and controls. Exploratory topographic analysis indicated that P300 amplitudes were not asymmetrical in patients, as has been observed with auditory P300s, and, unlike the performance measures, the P300s did not correlate with the patient's positive or negative symptom ratings. The implications of these findings are described in relation to attentional disturbances and trait versus state issues in schizophrenics.

P300 and stress in mild head injury patients

Objective: The P300 component of event-related potentials is affected by personal meaningfulness of the stimulus to the subject. Thus, the P300 component could provide an objective parameter in the emotional assessment of road accident mild head injury patients, when exposed to relevant stimuli. Methods: Thirteen patients with post-traumatic symptoms and 14 healthy controls were evaluated in this study. Two word types, distinguished by color, were presented on a computer screen in active `oddball' paradigm conditions. In the first subtest, the targets were accident-related (stressful) words; in the second subtest, the targets were non-accident-related (neutral) words. Target (20%) and non-target (80%) were defined by word color. Data recorded from Pz were analyzed for P300 parameters. Results: Patients and controls differed in their reaction to word types (group×word main effect P=0.0089), regardless of the oddball presentation. Overall, accident-related words produced a significantly larger P300 wave than neutral words in patients ( P=0.0001), but not in controls ( P=0.5741). Significant correlation was found between combined P300 amplitude difference (all stressful words vs. all neutral words) and the patient's Zung state anxiety score ( r=0.68, P=0.01). Conclusion: We suggest the P300 component can provide a useful, objective tool in the assessment of mild head injury patients.

275 Effects of film-induced emotions on n100 and P300 of a visually presented subsequent cognitive task

The aim of this study was to investigate whether P300 could predict the short-term prognosis of subjects at clinical high risk (CHR) for psychosis who do not convert to psychotic disorder (non-converters).CHR subjects were examined with auditory P300 at baseline, and their clinical state was regularly assessed up to 2 years. 45 CHR non-converters were divided into remitter and non-remitter groups. Repeated-measures analysis of variance (ANOVA) was performed to compare baseline P300 between the two groups. Multiple regression analysis was used to identify factors predicting symptomatic or functional improvement in CHR subjects during the follow-up period.There were no group differences in P300 amplitude or latency between CHR remitters and non-remitters. In the multiple regression analysis, P300 amplitude at Pz (β = 0.206, 95% confidence interval [95CI] = 0.035 to 0.567, p = 0.028) significantly predicted later amelioration of the Scale of Prodromal Symptoms (SOPS) negative symptoms. Improvement in SOPS general symptoms was significantly predicted by P300 amplitude at Pz (β = 0.255, 95CI = 0.065 to 0.455, p = 0.010) and mood stabilizer use (β = 0.199, 95CI = 0.081 to 4.154, p = 0.042).These results indicate that P300 may be a possible predictor of improvement in negative and general symptoms in CHR non-converters. Our findings support the recommendation that a broader concept of assessment guidelines is needed to forecast clinical outcome and provide appropriate interventions for CHR non-converters.

Individual differences in P300 amplitude: a genetic study in adolescent twins

Using quantitative genetic research designs, we decomposed phenotypic variance in P300 parameters into genetic and environmental components. The twin method was used to carry out this decomposition. Event related potentials (ERPs) were measured during a visual oddball paradigm in a sample of 213 adolescent twin pairs. The presence of male and female same-sex and opposite-sex twins in the sample enabled us to study sex differences in the contributions of genetic and environmental effects to P300 parameters. For targets and nontargets, half of the variance in the P300 amplitude is attributable to factors shared by the family members. However, it remains unclear whether this resemblance is attributable to shared environmental or genetic influences. The same factors (genetic or shared environmental) were found to contribute to the individual differences in males and females. The contributions do, however, differ across gender. Multivariate genetic analyses investigated the covariance among various brain areas to determine whether the covariance between two or more leads is attributable to the same genetic and/or the same environmental factors. The covariance of the P300 amplitude measured at different locations was attributable both to unshared environmental and to shared factors. Again it was not possible to show that the shared factors where either genetic or shared environmental.

Event-related potential negative shift in sons of polysubstance- and alcohol-use disorder fathers

Previous research has considered event-related potentials (ERPs) in relation to liability for alcohol and other substance use. This study explored ERPs in preadolescent boys at elevated risk for substance use due to paternal history of substance abuse or dependence. Sons (age 10–12) of fathers with an alcohol-use disorder (ALC, n = 29) were matched by age, IQ, education and parental alcohol use with sons of fathers with a polysubstance abuse or dependence diagnosis (POLY, n = 37). These two groups were matched with a low-risk comparison group (LOW, n = 29) of boys whose fathers had no substance-use disorder diagnosis. No boy in the study met criteria for a substance-use disorder. ERPs were collected from midline (Fz, Cz, Pz) and parietal (P3, P4) electrode leads during an auditory oddball task. ERPs of boys from the ALC and POLY groups showed a slow negative shift prominent at Cz and Pz. This negative shift, evident by 100 ms post-stimulus and lasting for the duration of the 1000-ms recording period, overlapped temporally with N1, N2 and P3 amplitude differences distinguishing the ALC and POLY groups from the LOW group. The ALC and POLY groups differed from each other in N2 amplitude at Cz, which was larger for ALC subjects. These findings offer a possible alternative explanation for previously observed amplitude anomalies noted in children at risk for substance-use disorders and suggest new avenues of inquiry.

Single trial variability within the P300 (250–500 ms) processing window in adolescents with attention deficit hyperactivity disorder

The traditional averaging process used to derive event related potential components (ERPs) is a soundly based method of determining the underlying ERP. Averaging, however, ignores the variability due to the single-trial ERPs that constitute the traditional average ERP. This variability may reflect complementary functional information to the average measure. Our group applied a simple procedure, the response variance curve (RVC), which measures single-trial ERP variability relative to their average. In this study, the average ERP and RVC measures (generated from the same single-trial task-relevant target ERPs) were assessed in an auditory oddball paradigm, in 17 unmedicated male adolescents with attention deficit hyperactivity disorder (ADHD) and in 17 age- and sex-matched normal controls. P300 amplitude, latency and point of maximum variability of the RVC were measured within the P300 processing window (250–500 ms post-stimulus). There were no significant differences in P300 amplitude or latency between the groups. Unmedicated ADHD patients, however, showed significantly increased single-trial variability within the P300 window compared with controls. This variability was significantly reduced with stimulant medication.

Electrophysiological indices of information processing in methylphenidate responders

Event-related potential (ERP) studies report that the positive deflection following stimulus evaluation at 300 msec (P3) in hyperactive children is augmented by methylphenidate (MP). This study investigates P3 and preceding ERP components using an auditory oddball task in attention-deficit hyperactivity disorder (ADHD). Mismatch negativity, negativity at 100 and 200 msec, and positivity at 200 msec and 300 msec (P3) were obtained from 14 control and hyperkinetic children. ADHD children who responded to MP were tested on two separate days while receiving either MP or placebo. Controls were tested once. No differences were found between groups for ERP components preceding P3. P3 amplitude was significantly larger under MP than under placebo, but did not differ from controls. Under MP, differences in P3 amplitude unexpectedly occurred when no response was required. A P3 amplitude increase under MP and the unexpected P3 suggest that MP affects attention regulation.

Neurophysiological intracerebral correlates of attentional and motor disengagement in man

In order to determine the effects of attention and distraction on painful and non-painful stimuli, the amplitude changes of 3 components (N150, P200, P300) of the Somatosensory event-related potential (SERF) elicited by painful and non-painful electrical stimuli were investigated. Painful and non-painful stimuli were determined using a visual analog scale. SERPs were recorded from 16 healthy volunteers at 5 midline and 4 left and 4 right hemispheric sites. The differences between the amplitudes of attended and ignored stimuli were quantified with a baseline-to-peak measure. ANOVA results revealed no significant attention or stimulus intensity effects for N150 but highly significant differences in P200 and P300 amplitudes between attended and ignored stimuli. In addition, P200 and P300 amplitudes were larger for strong stimuli than for weak stimuli, with no significant differences between non-painful and painful stimuli. These findings are consistent with the existence of a relative, rather than an absolute, relationship between SERP component amplitudes and subjective pain reports. Furthermore, the data give evidence that attentional manipulations represent a powerful method to decrease the perception of pain and that, when used with subjective and behavioral measures, the SERP represents a valuable asset in the multidimensional approach to pain measurement and assessment.

P300 assessment of opiate and cocaine users: Effects of detoxification and buprenorphine treatment

We assessed cognitive function following heroin and cocaine detoxification and investigated whether buprenorphine treatment improves the disruptive effects of detoxification. Three groups of male volunteers meeting DSM-III-R criteria for concurrent opiate and cocaine dependence were tested using an auditory oddball paradigm before and after detoxification, and again on the 15th day of either buprenorphine or placebo treatment. There were no significant differences in P300 amplitude, latency, or topographic distribution between drug-dependent subjects and controls on admission day. Following detoxification there was a significant decrease in P300 amplitude in the drug-dependent group at a time when self-reported signs of withdrawal were minimal. Buprenorphine treatment significantly reversed the P300 amplitude decrement following detoxification, whereas placebo-treated subjects continued to show depressed P300 amplitudes. These data demonstrate that buprenorphine treatment is effective in eliminating detoxification-induced impairments in one measure of cognitive ability.

P300 from one-, two-, and three-stimulus auditory paradigms

P300 event-related potentials (ERPs) from 1-, 2-, and 3-tone oddball paradigms were elicited and compared from the same subjects. In the 1-tone paradigm, only a target tone was presented, with the standard tone replaced by silence. The 2-tone paradigm was a typical oddball task, wherein the target and standard tones were presented every 2.0 s in a random order with a target-tone probability of 0.10. In the 3-tone paradigm, in addition to the infrequent target ( p = 0.10) and the frequent standard ( p = 0.80), infrequent nontarget tones ( p = 0.10) also were presented. The subject responded with a button press only to the target stimulus in each task. The target stimulus in each paradigm elicited a P300 component with a parietal maximum distribution. No P300 amplitude differences were found among paradigms, although peak latency from the 1-tone paradigm was shorter than those from the other two tasks. Both P300 peak amplitude and latency demonstrated strong positive correlations between each pair of paradigms. The results suggest that P300 was produced by the same neural and cognitive mechanisms across tasks. The possible utility of each paradigm in clinical testing is discussed.

Topography of Auditory and Visual P300 in Normal Adults

Auditory and visual P300 recordings were performed on 40 normal, right-handed individuals from age 16 through 65, using 31 evenly spaced scalp electrodes. Amplitude at the P300 peak and latency to this peak at each electrode site were measured. Age was significantly correlated with the 31-electrode mean for auditory and visual P300 amplitudes and auditory and visual P300 latencies. The younger age group (16-40) had shorter auditory and visual P300 latencies than the older group (41-65). Visual P300 amplitudes were of an overall larger magnitude than auditory P300 amplitudes. There were no other differences in P300 amplitudes or latencies by gender, modality, or side of scalp, and no significant topographical differences in P300 amplitudes or latencies by gender, age-group, modality, or side of scalp. Radial current density maps on group-averaged auditory and visual P300 waveforms at the group mean P300 latency at Cz, showed a right centroparietal sink surrounded by sources. This suggests a major right centroparietal P300 generator. Except for the change in P300 amplitudes with age, and the direction of the change in P300 latencies with age, these data on adults are similar to our previous description of P300 topography in normal children. Description of the normal topography of the P300, and demonstration of the lack of topographic differences by gender, age group, modality, or side of scalp, may facilitate the meaningful examination of P300 topography in cognitive disorders. Such an examination might lead to better diagnostic tools and more appropriate treatment of cognitive disorders in adults.

Premature disinhibition of P3 generation in schizophrenia

P300 (P3) is a long-latency cognitive event-related potential (ERP) elicited by relevant target stimuli. P3 was recorded from 11 schizophrenics and 13 normal controls during a cued visual continuous performance task (CPT-AX). Cue-target sequences were presented at short and long interstimulus intervals (ISIs), in order to investigate working memory in schizophrenia. There was no significant between-group difference in P3 amplitude to validly or invalidly cued targets at short ISI. In contrast, P3 amplitude to invalidly cued targets at long ISI was significantly greater in schizophrenics than in controls, suggesting decreased ability to encode or maintain inhibitory representations of stimulus context. P3 amplitude is typically reduced in schizophrenic subjects in the auditory modality, and normal or reduced in the visual modality. This study, which demonstrates a paradoxical P3 increase to targets at long ISI, suggests that P3 impairment in schizophrenia cannot be attributed solely to structural deficits within P3-generator regions.