Visual P300 Amplitude Research Articles

Amplitude of Visual P3 Event-Related Potential as a Phenotypic Marker for a Predisposition to Alcoholism

Recent data collected at six identical electrophysiological laboratories from the large national multisite Collaborative Study on the Genetics of Alcoholism provide evidence for considering the P3 amplitude of the event-related potential as a phenotypic marker for the risk of alcoholism. The distribution of P3 amplitude to target stimuli at the Pz electrode in individuals 16 years of age and over from 163 randomly ascertained control families (n = 687) was compared with those from 219 densely affected alcoholic families (n = 1276) in which three directly interviewed first-degree relatives met both DSM-III-R and Feighner criteria at the definite level for alcohol dependence (stage II). The control sample did not exclude individuals with psychiatric illness or alcoholism to obtain incidence rates of psychiatric disorders similar to those of the general population. P3 amplitude data from control families was converted to Z-scores, and a P3 amplitude beyond 2 SD's below the mean was considered an "abnormal trait." When age- and sex-matched distributions of P3 amplitude were compared, members of densely affected stage II families were more likely to manifest low P3 amplitudes (2 SD below the mean) than members of control families, comparing affected and unaffected offspring, and all individuals; all comparisons of these distributions between groups were significant (p < 0.00001). P3 amplitude means were also significantly lower in stage II family members, compared with control family members for all comparisons, namely probands, affected and unaffected individuals (p < 0.0001), and offspring (p < 0.01). Furthermore, affected individuals from stage II families, but not control families, had significantly lower P3 amplitudes than unaffected individuals (p < 0.001). Affected males from stage II families had significantly lower P3 amplitudes than affected females (p < 0.001). Recent linkage analyses indicate that visual P3 amplitude provides a biological phenotypic marker that has genetic underpinnings.

Measurement of P300 and sleep characteristics in patients with hypersomnia: do P300 latencies, P300 amplitudes, and multiple sleep latency and maintenance of wakefulness tests measure different factors?

To explore further the relationship between ease of falling asleep, ability to maintain wakefulness, attention and information processing in sleep apnea and other sleep disorders, we conducted a thorough analysis of the similarities, differences and correlations between auditory and visual P300 amplitudes and latencies, and tests of sleepiness. The 283 consecutive patients presenting with hypersomnia were administered nocturnal polysomnography. Next day they underwent auditory and visual P300 recordings, Multiple Sleep Latency Test (MSLT) and Maintenance of Wakefulness Test (MWT). Correlation coefficients were calculated between auditory and visual P300 amplitudes and latencies, respiratory disturbance index (RDI), sleep efficiency, % stage 1, and the tests for sleepiness. Factor analysis was performed with data from P300 testing, MSLT and MWT. Auditory P300 amplitude was correlated with sleep efficiency. Auditory P300 latency was correlated with % stage 1, RDI, MSLT and MWT. Visual P300 latency was correlated with % stage 1, sleep efficiency and MWT. MSLT but not MWT was negatively correlated with sleep efficiency. Factor analysis suggests three factors: attention, information processing, and sleepiness. We conclude that P300 latencies and tests of sleepiness (MSLT and MWT) measure different abilities in patients with diagnosable disorders of daytime sleepiness.

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.

Amplitude and area of the auditory P300 recorded with eyes open reflect remission of schizophrenia

Schizophrenic patients reportedly demonstrate smaller P300 amplitudes, which have been related to cognitive deficits, as well as structural and chemical abnormalities (Ford et al 1994a; Pritchard 1986). Auditory P300 amplitude is known to be resistant to changes in neuroleptic medication or clinical state, so it has been deemed a candidate for a trait marker for vulnerability to schizophrenia (Blackwood et al 1987; Eikmeir et al 1992; Ford et al 1994a, 1994b; Pritchard 1986). Duncan et al (1987), however, have shown that the visual P300 ampiitude is negatively correlated with clinical improvement as measured by brief psychiatric rating scale (BPRS) scores. Thus they suggested that visual P300 amplitude may serve as a state marker in schizophrenia (Duncan et al 1987). We recorded serial sessions of auditory event-related potentials (ERPs) in schizophrenic patients during the course of their treatment for up to 6 months following admission. Since withinsession and between-session reliabilities of P300 measures recorded with eyes open are usually higher than those recorded with eyes closed (Maeda et al 1995), eyes-open and eyes-closed recordings were both made to provide further data regarding the long-term reliability of P300 recorded under these two sets of conditions. In addition, P300 area seems to be more reliable than P300 amplitude (Maeda et al 1995), so P300 area was measured as well.

A Simple Auditory Oddball Task in Young Adult Males at High Risk for Alcoholism

The reduction in the amplitude of the auditory P300 in young adult males at high risk for alcoholism has not been as consistently replicated as has been the reduction in the visual P300 amplitude in the same group. The easier nature of the auditory task was thought to be responsible for the inconsistency. We examined the auditory P300 amplitude in a group that has not yet been studied, young adult sons of alcoholics (mean age = 24.9 years, n = 48), and compared them with age and sex-matched controls (mean age = 27.8 years, n = 23). We found the auditory P300 amplitude to be reduced in the high-risk group and this reduction to be the greatest over the posterior centroparietal and occipital areas when individual leads were examined. We further analyzed the data using current source density, a mathematical transformation that circumvents some of the errors inherent in measuring scalp-evoked potentials, and found reduced current source density in the high-risk group in the posterior central and parietal areas. Thus, we found that a simple auditory oddball task was effective in eliciting P300 differences in groups at high and low risk for alcoholism. The clinical significance of the P300 is discussed, as well as the relevance of task difficulty in eliciting auditory P300 differences in young males at high risk for alcoholism.

Topography of auditory and visual P300 in normal children.

Auditory and visual P300 recordings were performed on 39 normal, right-handed individuals from age 6 through 15, 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 latencies, but not for amplitudes. The younger age group (6-10) had longer auditory and visual P300 latencies than the older age group. Visual P300 amplitudes were of an overall larger magnitude than auditory amplitudes. There were no other differences including 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. 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 children.

Tc99m HMPAO brain SPECT with visuospatial and verbal activation in normal subjects

The P300 component of the event-related brain potential (ERP) is reduced in schizophrenia. Cross--sectional analyses suggest smaller P300 amplitudes are associated with worse clinical status. We used a longitudinal design to ask if P300 is a stable reflection of chronic severity or if it tracks short-term clinical fluctuations. Thirty-six male veterans with schizophrenia (DSM-III-R) participated in as many as seven ERP sessions, under various medication regimens, and sometimes over multiple hospitalizations. ERPs were collected during auditory and visual paradigms in which frequent events occurred on 80% of the trials, and rare events on 20%. Subjects pressed a button in response to rare events. The clinical status of the subject was assessed within several days of each ERP session using the Brief Psychiatric Rating Scale (BPRS). Relationships between P300 and clinical status were addressed using hierarchical multiple regression analyses in which BPRS scores were regressed on Subject, P300 (amplitude or latency), and their interaction. In no case was the interaction term significant, allowing a common slope of the BPRS-P300 regression lines to be assumed across subjects. The Subject effect was entered into the regression analysis at the first step, controlling for BPRS variation associated with intersubject differences, leaving only within-subject variation over time as the source of BPRS variance available for prediction. At the second step, P300 measures were entered and the increment in R 2 tested. Auditory and visual P300 amplitude, but not latency, significantly predicted total BPRS scores, but not positive or negative symptom subscores. Thus, within an individual patient over time, increases in both auditory and visual P300 amplitude track clinical improvement. (Supported by NIMH (MH30854) & Department of Veterans Affairs.) 285. Tc99m HMPAO BRAIN SPECT WITH VISUOSPATIAL AND VERBAL ACTIVATION IN NORMAL SUBJECTS

Auditory and visual P300 event related potentials are not altered in medically and psychiatrically normal chronic marihuana users

Attempts to use Event Related Potentials, particularly the cognitive or P300 evoked potential, as measures of CNS effects of THC use have been infrequent and have produced inconsistent results. We published a pilot study in which psychiatric patient THC users had significantly prolonged auditory P300 latencies and reduced amplitudes as contrasted with non-users. Because psychiatric diagnoses and medication effects could not be controlled, we repeated the study with medically and psychiatrically normal subjects selected with extremely stringent exclusion criteria and screening procedures. P300 latency differences between THC users and controls were not detected. Using all subjects, THC users displayed reduced auditory and visual P300 amplitudes. However, when age differences between THC users and controls were removed, all significant P300 amplitude differences were removed as well. The contaminating effect of using psychiatric patients in THC research is discussed and the importance of using carefully screened normal subjects in studies of neurophysiological abuse drug effects is stressed.

Season, gender, and P300

Light therapy in patients with seasonal affective disorder has been reported to enhance visual P300 amplitude. This finding raises the possibility that variations in P300 occur naturally in nonpatients as a function of seasonal variation in sunlight. In the present investigation, P300 was studied in a sample of psychiatrically screened normal subjects who were tested at different times of the year. P300 was larger in women than men and varied in relation to season. This pattern is relevant to studies in which subjects are tested under varying sunlight conditions, such as different seasons. In addition, variations in P300 in normal subjects may be relevant to an understanding of the effectiveness of light therapy for patients with seasonal affective disorder.

P3 in Schizophrenia Is Affected by Stimulus Modality, Response Requirements, Medication Status, and Negative Symptoms

Eighteen schizophrenics who were not taking medication, 13 schizophrenics who were taking medication, and 37 age-matched controls were tested with event-related potential paradigms designed to elicit P3 response automatically or effortfully (ie, with a choice reaction time task). Electroencephalograms were recorded from the 19 standard 10-20 electrode sites. Compared with controls, both groups of schizophrenics had reduced P3 amplitudes for both effortful and automatic paradigms. P3 latencies were delayed relative to controls for the medication-taking schizophrenics in the effortful paradigms. Negative symptoms derived from the Brief Psychiatric Rating Scale within 1 week of event-related potential testing correlated negatively with both auditory and visual P3 amplitude in the subjects who were not taking medication. There was no evidence that P3 is smaller over left temporal electrode sites in schizophrenics, as has been reported by others. P3 amplitude reduction in schizophrenia is a robust psychobiological phenomenon that is present regardless of medication status or task demands.

Auditory and visual P300s in temporal lobectomy patients: evidence for modality-dependent generators.

The P300 component of the event-related brain potential (ERP) was studied in epileptic patients with unilateral resections of medial temporal lobe areas of the brain. The patients and controls were tested in an oddball paradigm in two conditions: counting and reaction time. Both auditory and visual stimuli were used to elicit ERP activity in different blocks. Despite the reported presence of locally-generated auditory and visual P300-like potentials in these areas, no evidence was found of any surgically-related hemispheric asymmetries in the scalp distribution of the P300 or Slow Wave for stimuli in either modality. Moreover, compared to normal controls, there were no significant reductions in overall P300 amplitude in the patients. The patients did show a double dissociation in their frontal ERP activity: the left temporal lobectomy patients showed apparent decreased frontal auditory P300 amplitudes but normal visual P300 amplitudes, whereas the right temporal lobectomy patients showed the opposite pattern. These results appeared to be due to the presence of a long-duration slow wave rather than to alterations in P300 amplitude. These data do not support the presence of a significant contribution by a hippocampal/amygdala generator to the activity of the scalp-recorded P300 in the oddball paradigm. Topographic comparisons on normalized amplitudes revealed significantly different scalp distributions as a function of stimulus modality, event probability, and task for both the P300 and Slow Wave components. These data indicate that the amplitude variations associated with each experimental variable are due to the activity of a separate underlying neural source. The sources of task and probability effects on P300 and Slow Wave amplitude each appeared to be modality-independent generators. The nature of the third, modality-related generator is less clear. These results uphold the tenets of the model of P300 amplitude proposed by Johnson (1986) and argue against the idea that the P300 is a unitary phenomenon.

The relationship between neuropsychological and late component evoked potential measures in chronic alcoholics.

The relationships between event-related potential (ERP) measures and neuropsychological measures were investigated in a group of 39 male alcoholics and 22 age-matched male controls. Late component ERP measures such as N1, Nd, and P3 components and neuropsychological measures of perceptual-motor function, semantic and figural memory and verbal abstracting functions were included in a correlational analysis. No significant correlations between N1 amplitude or latency and neuropsychological tests were obtained. However, visual Nd amplitude correlated significantly with perceptual-motor tests and figural memory scores in the alcoholics. Significant correlations were found in alcoholics for visual P3 amplitude at PZ and delayed figural memory scores and two of the perceptual-motor tests. No significant correlations were obtained among the controls. These data indicate that significant relationships exist between some neuropsychological and ERP measures but that these relationships are restricted to measures of perceptual-motor functioning and to delayed figural memory.

No decrement in visual P300 amplitude during extended performance of the oddball task.

Research indicates that in visual sustained attention paradigms, the amplitude of the P300 component of the event-related potential invoked by target (critical) stimuli shows a decrement in amplitude. This amplitude decrement parallels decrements in vigilance performance that result from the difficult discrimination that is typically required between the infrequent targets and the frequent nontargets (neutral stimuli). In contrast, target stimulus P300 does not appear to show a decrement across large numbers of trials during performance of the "oddball" paradigm, in which targets and nontargets are highly discriminable. The present study measured target and nontarget P300 amplitude during performance of a visual oddball paradigm extended over an interval of some 3 1/2 hours, a period well in excess of the 3/4 hour intervals employed in previous research. The results indicated no decrement in P300 amplitude as a function of time for either targets or nontargets. The only significant relationship between P300 and behavioral data was an inverse correlation across oddball runs between average nontarget P300 amplitude and total number of targets missed.