Effect of alcohol and task on hemispheric asymmetry of visually evoked potentials in man.

The study examined the effect of a dose of alcohol producing a mean blood alcohol content of 90 mg% on components of the scalp-recorded visually evoked potential (VEP) both with and without a visual discrimination task to control the level of attention, and the interaction of amplitudinal hemispheric asymmetry of the VEP with alcohol treatment and the discrimination task. Ingestion of ethyl alcohol producing a mean blood alcohol content of 90 mg% affected VEPs recorded from the central scalp by attenuating the overall amplitude of the later VEP components (60-200 msec) and by significantly reducing hemispheric asymmetry in the amplitude of these VEP components. Alcohol attenuates VEP components P90-N120 and N120-P180, and the task of counting flashes and attending to discriminate double flashes increased amplitude of VEP components N60-P90 and P90-N120 in control and placebo conditions. Several studies have reported that the VEP recorded from the right hemisphere of human beings is larger than the VEP recorded from the homologous location in the left hemisphere. Evoked potentials recorded under control and placebo conditions in this study also demonstrated a hemispheric asymmetry with right larger than left for component P90-N120. We also found a reliable alcohol by hemispheric asymmetry interaction. Alcohol selectively depressed the amplitude of the right hemisphere VEP (P90-N120) component to a significantly greater extent than the left hemisphere VEP was affected.     

Quantitative EEG and cognitive evoked potentials in anemia.

OBJECTIVE: The anemic status may alter brain functions and electrogenesis, as reflected by EEG and cognitive EPs (CEPs). This study aims to evaluate CEPs and EEG power spectra in adult patients with iron-deficiency anemia and to determine the effects of appropriate iron therapy on electrodiagnostic findings. METHODS: Fifty-one patients with iron-deficiency anemia underwent CEP and EEG recording. All patients were re-assessed after three months of oral-iron therapy. RESULTS: All patients had recovered from their anemia through the three-month iron therapy. Central N1 amplitude and parietal P2 amplitude was increased. N2 latencies were shortened in frontal and central regions. P3 latencies were shortened in frontal, central and parietal areas and P3 amplitude was increased in the parietal region. Except in the gamma-band, all pretreatment and post-treatment mean-power values were significantly lower at the temporal, parietal and occipital regions. CONCLUSIONS: This study indicates that in iron-deficiency anemia, appropriate iron therapy can improve brain electrogenesis, as reflected by P300 and EEG power spectra.     

Cerebrovascular accident alters P300 event-related potential characteristics

P300 event-related potentials to counted (target) and uncounted (background) visual stimuli were recorded from subjects who had sustained either a right or a left middle cerebral artery cerebrovascular accident (CVA) and from appropriate normal control subjects. Subjects were asked to count target stimuli and to ignore non-target stimuli. Standard measurements of the amplitude and latency of P300 components as well as intercorrelations among P300 wave forms from 3 brain regions (Fz, Cz, Pz) were collected. Amplitudes of N1-P2 and N2-P3 components as well as overall amplitude of the ERP wave form were reliably reduced by a CVA, but component latencies were not significantly affected. The amplitude reduction associated with a CVA cannot be simply interpreted as evidence for reduced cognitive efficiency because overall amplitudes and intercorrelations between brain regions of CVA patients were reduced for both counted and uncounted stimuli. The intercorrelations between brain regions were particularly reduced if the CVA was localized in the right hemisphere. For CVA patients, reduced component amplitudes may reflect decreased cortical intercommunication associated with damage to subcortical brain structures.     

Analysis of magnetic source localization of P300 using the multiple signal classification algorithm

The authors studied the localization of P300 magnetic sources using the multiple signal classification (MUSIC) algorithm. Six healthy subjects (aged 24-34 years old) were investigated with 148-channel whole-head type magnetencephalography using an auditory oddball paradigm in passive mode. The authors also compared six stimulus combinations in order to find the optimal stimulus parameters for P300 magnetic field (P300m) in passive mode. Bilateral MUSIC peaks were located on the mesial temporal, superior temporal and parietal lobes. Interestingly, all MUSIC peaks in these regions emerged earlier in the right hemisphere than in the left hemisphere, suggesting that the right hemisphere has predominance over the left in the processing activity associated with P300m. There were no significant differences among the six stimulus combinations in evoking those P300m sources. The results of the present study suggest that the MUSIC algorithm could be a useful tool for analysis of the time-course of P300m.     

Inter- and intra-hemispheric processing of visual event-related potentials in the absence of the corpus callosum

Interhemispheric differences of the N100 latency in visual evoked potentials have been used to estimate interhemispheric transfer time (e.g., Saron & Davidson, 1989). Recent work has also suggested that the P300 component could reflect the efficacy of interhemispheric transmission (Polich & Hoffman, 1998). The purpose of the present study was to study the differential role of the corpus callosum (CC) and anterior commissure (AC) in the interhemispheric propagation of these two electrophysiological components. Thus, the amplitude and latency distribution of the N100 and P300 components were analyzed using high-density electrical mapping in a subject with agenesis of CC but preservation of AC, a subject with agenesis of both CC and AC, and 10 neurologically intact control subjects. The task consisted of a modified visual oddball paradigm comprising one frequent and two rare stimuli, one presented on the same and the other on the opposite side of the frequent stimulus. Interhemispheric differences in latency were found for the N100 component in controls. However, in the acallosal subjects, this component was not identifiable in the indirectly stimulated hemisphere. In controls, no interhemispheric differences were observed in the distribution of the P300 latency and amplitude to rare and frequent stimuli. The distribution of the P300 amplitude in the acallosal subject with an AC was identical to that of the controls, whereas in the acallosal subject lacking the AC, the amplitude was greater in the hemisphere receiving the frequent stimuli, regardless of the visual hemifield in which the rare stimuli were presented. In both acallosal subjects, hemispheric differences in the P300 latency were observed, the latencies being shorter in the hemisphere directly stimulated for all categories of stimuli. These results suggest that the interhemispheric transfer of both the N100 and P300 components relies on the integrity of cortical commissures. Possible P300 generator sources are discussed.     

P300 and genetic risk for schizophrenia

BACKGROUND: We assessed the suitability of event-related potential frontal and temporoparietal P300 changes as intermediate phenotypes in genetic studies of schizophrenia. We applied a principal component analysis approach based on the notion that P300 abnormalities in siblings of schizophrenic patients may involve a widespread network of relatively weak cortical generators and because an earlier, smaller study that used a topographic analysis of covariance model did not show that localized P300 changes predict risk for schizophrenia. METHODS: P300 changes in 66 schizophrenic patients, 115 healthy siblings of schizophrenic patients, and 89 unrelated controls were studied during a standard auditory oddball paradigm. Principal components were calculated across electrodes, revealing frontal and temporoparietal components for latency and amplitude, respectively. For the frontal and temporoparietal P300 amplitude and latency components, the intraclass correlations (ICCs) between sib-pairs (pairs of unaffected siblings and schizophrenic index patients) and the relative risk ratios (lambda) were determined. RESULTS: Compared with controls, schizophrenic patients and their unaffected siblings showed significant reductions in the temporoparietal P300 amplitude component. Both groups were also characterized by a significantly higher frontal P300 amplitude component. Significant ICCs and increased relative risk ratios were found for the frontal (ICCU = 0.18; P =.04; lambda = 3.4) and temporoparietal (ICCU = 0.24; P =.01; lambda = 1.7) P300 amplitude components. CONCLUSIONS: Temporoparietal P300 amplitude reduction and frontal P300 amplitude increase seem to be quantitative phenotypes associated with increased risk of schizophrenia. Both measures may be useful for increasing the statistical power of genetic studies of schizophrenia.     

Clinical and neuropsychological correlates of the P300 in schizophrenia

We investigated the relationship between the P300, neuropsychological test performance and symptomatology in recent-onset schizophrenic patients (n = 45) to gain insight into underlying mechanisms of abnormal P300 in schizophrenia. The P300 was recorded in two sessions with an intermission of five minutes, at the midline frontal, central and parietal electrode site. P300 amplitude and latency were compared with those obtained in 25 controls. Twenty patients were treated with olanzapine and 19 patients with risperidone. P300 amplitude was smaller and latency longer in patients than in controls. In the patient group, parietal P300 amplitude reduction was related to poorer performance on neuropsychological tests of memory. Frontal P300 amplitude reduction was related to impaired selective attention. In patients with negative symptomatology, P300 amplitude was reduced in the second P300 session compared with the first. Patients on risperidone demonstrated a smaller parietal P300 amplitude than patients using olanzapine. Reduced parietal P300 amplitude could signify a dysfunction in the continuous memory updating of current events. Negative symptomatology may be associated with a time dependent decrease in neuronal firing, as indicated by reduced P300 amplitude in the second P300 session.     

Neurophysiological signals of working memory in normal aging

To examine how neurophysiological signals of working memory (WM) change with normal aging, we recorded EEGs from healthy groups (n=10 each) of young (mean age=21 years), middle-aged (mean=47 years), and older (mean=69 years) adults. EEGs were recorded while subjects performed easy and difficult versions of a spatial WM task. Groups were matched for IQ (mean=123; WAIS-R) and practiced in task performance. Responses slowed with age, particularly in the more difficult task. Advanced age was associated with decreased amplitude and increased latency of the parietal P300 component of the event-related potential and an increase in the amplitude of a frontal P200 component. Spectral features of the EEG also differed between groups. Younger subjects displayed an increase in the frontal midline θ rhythm with increased task difficulty, a result not observed in older subjects. Age-related changes were also observed in the task-related alpha signal, the amplitude of which decreases as more neurons become involved in task-related processing. Young adults showed a decrease in alpha power with increased task difficulty over parietal regions but not over frontal regions. Middle-aged and older adults showed decreased alpha power with increased task difficulty over both frontal and parietal regions. This suggests that normal aging may be associated with changes in the fronto-parietal networks involved with spatial WM processes. Younger subjects appear to use a strategy that relies on parietal areas involved with spatial processing, whereas older subjects appear to use a strategy that relies more on frontal areas.     

A model for P300 generation based on responses to near-threshold visual stimuli

Near-threshold and suprathreshold visual ERPs and their frequency components were compared with the aim to obtain further information on the generation mechanism of the P300 wave. Decrease of the stimulus energy from suprathreshold to near-threshold level resulted in an increase of the P300 amplitude specifically in the occipital region. This finding was in contrast with the P300 amplitude decrease in central and frontal regions and its constancy in parietal area. Delta and theta responses showed a similar distribution pattern, whereas alpha responses decreased in all regions as the stimulus energy decreased. We conclude that P300 wave may correspond to a delta oscillation during a widespread, transient interruption of afferent inputs from subcortical structures to the cortical neurons including those in the visual sensory area and simultaneous increase of the cortico-cortical interactions. If visual inputs are of suprathreshold strength, they override this effect specifically in the primary visual area and disrupt the cortico-cortical interactions and the emergence of P300 in the occipital cortex.     

Impaired early visual response modulations to spatial information in chronic schizophrenia

Early visual processing stages have been demonstrated to be impaired in schizophrenia patients and their first-degree relatives. The amplitude and topography of the P1 component of the visual evoked potential (VEP) are both affected; the latter of which indicates alterations in active brain networks between populations. At least two issues remain unresolved. First, the specificity of this deficit (and suitability as an endophenotype) has yet to be established, with evidence for impaired P1 responses in other clinical populations. Second, it remains unknown whether schizophrenia patients exhibit intact functional modulation of the P1 VEP component; an aspect that may assist in distinguishing effects specific to schizophrenia. We applied electrical neuroimaging analyses to VEPs from chronic schizophrenia patients and healthy controls in response to variation in the parafoveal spatial extent of stimuli. Healthy controls demonstrated robust modulation of the VEP strength and topography as a function of the spatial extent of stimuli during the P1 component. By contrast, no such modulations were evident at early latencies in the responses from patients with schizophrenia. Source estimations localized these deficits to the left precuneus and medial inferior parietal cortex. These findings provide insights on potential underlying low-level impairments in schizophrenia.     

The intracranial topography of the P3 event-related potential elicited during auditory oddball.

In order to isolate the anatomical locus of neural activity primarily responsible for generating the scalp-recorded P3 (or P300), the topography of event-related potentials (ERPs) elicited during an auditory oddball task was compared between medial-to-lateral aspects of the frontal, parietal, and temporal lobes in 10 epileptic patients undergoing stereoelectroencephalography for seizure localization. Evidence of local ERP generation was obtained from each of these areas. Small amplitude P3-type potentials were sometimes observed to invert polarity across recording contacts in the frontal lobe. Large amplitude positive polarity P3-type components were observed in the lateral neocortex of the inferior parietal lobule (IPL), that rapidly attenuated in amplitude at more anterior, posterior, superior, inferior, and medial recording contacts. Large amplitude polarity inverting P3-type components were also observed to be highly localized to hippocampal contacts of temporal lobe electrodes. These data are discussed in the context of other recent studies of lesion effects, scalp topography, and intracranial recordings, and it is concluded that activity generated in the IPL is likely to make the major contribution to the scalp-recorded P3, with smaller contributions from these other sources. Finally, salient topographical differences between the intracranial distribution of the P3 and those of the N2 (or N200) and slow wave (SW) suggest that the generators of these components are not identical.     

Attention to central and peripheral visual space in a movement detection task: an event-related potential and behavioral study. I. Normal hearing adults

The effects of focussed attention to peripherally and centrally located visual stimuli were compared via an analysis of event-related brain potentials (ERPs) while subjects detected the direction of motion of a white square in a specified location. While attention to both peripheral and foveal stimuli produced enhancements of the early ERP components, the distribution over the scalp of the attention-related changes varied according to stimulus location. The attention-related increase in the amplitude of the N1 wave (157 ms) to the peripheral stimuli was greater over the parietal region of the hemisphere contralateral to the attended visual field. By contrast, the largest effects of foveally directed attention occurred over the occipital regions where the increase was bilaterally symmetrical. Additionally, the effects of attention on the ERPs were significantly larger for moving than for stationary stimuli, and this effect was greater for peripheral than for central attention. A long-latency positive displacement component (300-600 ms) was larger over the right than the left hemisphere during attention to the lateral visual fields, but was symmetrical in amplitude when central stimuli were attended. These results suggest that different pathways are modulated when attention is deployed to different regions of the visual fields. Further, they suggest that the special role of the right hemisphere in spatial attention may be limited to analysis of information in the visual periphery.     

Visual evoked potentials to lateralized visual stimuli and the measurement of interhemispheric transmission time

Visual evoked potentials (VEPs) to lateralized light flashes were recorded from the parietal midline, and from homologous occipital and central sites, in a GO/NOGO reaction time task. The N160 component of the VEP was found to be larger over the hemisphere contralateral to the visual field of stimulus exposure at all pairs of lateral electrodes. At the occipital sites only, N160 latency was also shorter from the contralateral hemisphere, by an average of approximately 14msec. This was not so centrally, where a non-significant value of approximately 4 msec was obtained. These data are considered to be consistent with Milner and Lines' hypothesis that callosal transmission occurs at different rates in different functional regions of the corpus callosum.     

Interhemispheric interzonal connections in the parietal cortex

In acute experiments on cats immobilized by tubarine transcallosal responses (TCRs) to the stimulation of the visual or auditory cortex of the opposite hemisphere were investigated in the parietal associative region. It was found that interzonal heterotopical TCRs could be recorded along the entire surface of the parietal cortex and were in two forms: positive-negative or negative-positive. Positive-negative evoked potentials (EPs) had greater latent periods. Negative-positive TCRs disappeared after the corpus callosum section or after the section of intracortical pathways on the side of recording and/or stimulation. EPs with initial positivity changed insignificantly as a result of these operations. Interzonal TCRs were characterized by the presence of interhemispheric asymmetry. The amplitude of early components in visual-parietal EPs of any configuration appeared to be greater in the right hemisphere. These responses also had a greater latent period. According to the magnitude of the late positive wave in visual-parietal TCRs the left hemisphere appeared to be dominant. Interhemispheric asymmetry in audioparietal EPs was individual. The amplitude of the early positive component prevailed as to magnitude in the right hemisphere in males and in the left hemisphere in females. The late negative wave in animals of either sex was greater in the right hemisphere. The peculiarities of generation and interhemispheric asymmetry of different components in visual-parietal and audioparietal TCRs are discussed. A symmetricising function of the parietal associative cortex is suggested.     

Intracortical generators of the flash VEP in monkeys

Flash visual evoked potentials (VEPs) in unanesthetized monkeys were recorded from the cortical surface and from closely spaced intracortical sites together with associated multiple unit activity (MUA). The VEP depth profiles were subjected to current source density (CSD) analysis to delineate the laminar pattern of transmembrane current flows manifested by extracellular source and sinks. The initial surface recorded components (P15 and P18) were generated subcortically within the thalamocortical radiations. The distribution of current sources and sinks associated with two subsequent surface negative components. N24 and N40. demonstrates their generation within laminae IVA and IVCb respectively, both parvocellular thalamorecipient layers. Oscillatory potentials resembling those seen in human VEPs are observed riding on N40; analysis of MUA in conjunction with sources and sinks coincident with these wavelets provides evidence that they derive from both thalamocortical and cortical activity. MUA in the 20-60 msec range shows phasic increases throughout lamina IV, which are maximum in amplitude within lamina IVA. This increased firing is concurrent with the sinks observed within the parvocellular thalamorecipient sublaminae IVCb and IVA. A subsequent component, P65, coincident with a decrease in MUA to below the spontaneous level co-located with a lamina IVCb current source, probably arises from intracortically generated inhibitory activity within IVCb. The next VEP component, a surface negative potential at 95 msec, is coincident with current sources and sinks in lamina III, and is consistent with stellate cell input to supragranular elements. VEP components after N95 are not associated with either MUA or CSD activity and are probably generated in extrastriate cortex. Human counterparts of the simian VEP are proposed.     

Cortical sources of the early components of the visual evoked potential

This study aimed to characterize the neural generators of the early components of the visual evoked potential (VEP) to isoluminant checkerboard stimuli. Multichannel scalp recordings, retinotopic mapping and dipole modeling techniques were used to estimate the locations of the cortical sources giving rise to the early C1, P1, and N1 components. Dipole locations were matched to anatomical brain regions visualized in structural magnetic resonance imaging (MRI) and to functional MRI (fMRI) activations elicited by the same stimuli. These converging methods confirmed previous reports that the C1 component (onset latency 55 msec; peak latency 90-92 msec) was generated in the primary visual area (striate cortex; area 17). The early phase of the P1 component (onset latency 72-80 msec; peak latency 98-110 msec) was localized to sources in dorsal extrastriate cortex of the middle occipital gyrus, while the late phase of the P1 component (onset latency 110-120 msec; peak latency 136-146 msec) was localized to ventral extrastriate cortex of the fusiform gyrus. Among the N1 subcomponents, the posterior N150 could be accounted for by the same dipolar source as the early P1, while the anterior N155 was localized to a deep source in the parietal lobe. These findings clarify the anatomical origin of these VEP components, which have been studied extensively in relation to visual-perceptual processes.     

Neural correlates of chromostereopsis: An evoked potential study

Chromostereopsis is an illusion of depth arising from colour contrast: ocular chromatic aberrations usually make red appear closer to the viewer than blue. Whereas this phenomenon is widely documented from the optical and psychophysical point of view, its neural correlates have not been investigated. To determine the cortical processing of this colour-based depth effect, visual evoked potentials (VEPs) to contrasts of colour were recorded in 25 subjects. Chromostereopsis was found with the stimuli combining spectra extremes. VEP amplitude but not latency effects were observed to colour depth cues, suggesting an underlying, depth-specific slow negative wave, located using source modelling first in occipito-parietal, parietal, then temporal areas. The component was larger over the right hemisphere consistent with RH dominance in depth processing, likely due to context-dependent top-down modulation. These results demonstrate that the depth illusion obtained from contrast of colour implicates similar cortical areas as classic binocular depth perception.     

Electro-oculographic and electroencephalographic correlative study of optokinetic responses in brain lesions.

Electro-oculograms of induced optokinetic responses (OKR) and EEG were recorded in 61 patients with either left or right hemisphere lesions. Of the 61 patients 55 showed focal EEG disturbances as follows: occipito-temporal (7 cases), parieto-temporal (10 cases), occipito-parieto-temporal (26 cases), temporal (9 cases) and frontal (3 cases). Symmetric OKR (21 cases) were recorded when no EEG changes were observed or when these were localized to left or right temporal and frontal electrodes and exceptionally when unilateral occipital and parietal regions were also involved. In 40 cases with unilateral hemispheric lesion a contralateral abnormal OKR was observed. Low frequency OKR with or without amplitude changes, especially of fast (saccadic) component, was mainly observed in parietal localization. In severely disturbed OKR, i.e. random jerks, the abnormal brain waves were mainly localized to the occipito-parieto-temporal region. In all cases in which no response was obtained the affected area was the occipito-parieto-temporal. These findings are discussed with reference to the regulating systems of slow (smooth) and fast (saccadic) eye movements triggered by visual stimuli.     

The P300 event-related potentials in dementia of the Alzheimer type. Correlations between P300 and monoamine metabolites.

We studied auditory event-related potentials (ERPs) in 40 patients with dementia of the Alzheimer type (DAT). Peak latencies and amplitudes of N100, P200 and P300 components were measured. To study the possible relationships between the ERPs and monoaminergic neurotransmitter functions, CSF neurotransmitter metabolites were also analyzed. In patients with DAT, the P300 amplitude was significantly reduced and the P300 latency was prolonged. CSF concentrations of 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) were decreased. The P300 amplitude was significantly correlated with the 5-HIAA concentration. There were no correlations between the P300 components and the HVA concentration. These findings suggest that the serotonergic system modulates the P300 component of ERPs in patients with DAT.     

Topographic mapping of cognitive event-related potentials in a double-blind, placebo-controlled study with the hemoderivative Actovegin in age-associated memory impairment

In a double-blind placebo-controlled study, the effects of Actovegin on cognitive event-related potentials were studied in 18 age-associated memory impairment (AAMI) patients. Actovegin is a protein-free metabolically active hemoderivative improving oxygen and glucose utilization. Each patient was treated, in randomized order, for 2 weeks with 250 ml 20% Actovegin and 250 ml placebo daily with an interval of 3 weeks in between. Psychophysiological tests were carried out by means of the Viennese Psychophysiological Test System (VPTS) before as well as 5 h after the administration of one single infusion on day 1 (acute effect), before (subacute effect) as well as after one additional superimposed infusion on day 15 (superimposed effect). There was no effect on earlier stages of information processing measured by N1 and P2 component of nontarget ERP nor on ERP latencies. However, P300 amplitude increased after acute, subacute as well as superimposed infusion of Actovegin as compared to placebo, confirming the hypothesis that nootropic drugs may influence the P300 amplitude in the sense of an improved availability of cognitive processing resources. This increase of P300 amplitude (up to 4.8 microV), seen specifically in central and parietal regions, proved to be significant in a confirmatory test.