Clinical application of the P3 component of event-related potentials. I. Normal aging

Normal adult volunteer subjects ranging in age from 18 to 90 years participated in a study in which analogous auditory and visual paradigms, with infrequently occurring target and non-target events, were used to elicit event-related potentials (ERPs) with a prominent P3 component. Of the 135 subjects participating, 66 completed both auditory and visual paradigms. The amplitude and latency of P3 were analyzed using average ERPs, single trials (adaptive filter) and principal components analysis (PCA). Age regressions were calculated using measures derived from average ERPs and single trials. Single trial measures were better than average ERP measures in demonstrating age-related changes in P3 latency. There was a significant increase in P3 latency with age of 1–1.5 msec/year. The range of normal P3 latency for a given age (1 S.E. of the regression = 40 msec for the visual target stimuli) was much larger than obtained by other investigators.The visual paradigm produced higher P3 latency/age correlations than the auditory paradigm (visual target r = 0.52, non-target r = 0.42; auditory target r = 0.32, non-target r = 0.33). Within individuals, the amplitude and latency of P3 generated by auditory and visual stimuli were highly correlated, though the visual paradigm produced larger and later P3s than the auditory paradigm.There is an apparent change in the scalp topography of P3 with age. In young adults, P3s to target stimuli have a markedly parietal distribution. The distribution of P3 becomes more uniformly distributed from Pz to Fz with age. This may be due to changes in overlapping components such as the slow wave (SW) rather than to changes in the amplitude of P3 per se.     

P300 assessment of early Alzheimer's disease

The P300 (P3) event-related brain potential (ERP) was elicited in 16 demented patients presumed to be in the early stages of Alzheimer's disease and 16 normal control subjects well matched for age, sex, education and occupational level. All subjects performed a simple auditory discrimination task in which a target tone was presented randomly on 20% of the trials. P3 amplitude was smaller and peak latency longer for the Alzheimer patients compared to control subjects. A second ERP task also was administered in which the target tone occurred 50% of the time. Analysis of the target/standard tone presentation sequences indicated that the Alzheimer patient group demonstrated less amplitude difference between the target and standard sequences and longer overall latencies compared to the control group. The results that the P3 ERP component from auditory stimuli can provide useful information about Alzheimer's disease during its early stages.     

Prediction of Auditory and Visual P300 Brain-Computer Interface Aptitude

Objective

Brain-computer interfaces (BCIs) provide a non-muscular communication channel for patients with late-stage motoneuron disease (e.g., amyotrophic lateral sclerosis (ALS)) or otherwise motor impaired people and are also used for motor rehabilitation in chronic stroke. Differences in the ability to use a BCI vary from person to person and from session to session. A reliable predictor of aptitude would allow for the selection of suitable BCI paradigms. For this reason, we investigated whether P300 BCI aptitude could be predicted from a short experiment with a standard auditory oddball.

Methods

Forty healthy participants performed an electroencephalography (EEG) based visual and auditory P300-BCI spelling task in a single session. In addition, prior to each session an auditory oddball was presented. Features extracted from the auditory oddball were analyzed with respect to predictive power for BCI aptitude.

Results

Correlation between auditory oddball response and P300 BCI accuracy revealed a strong relationship between accuracy and N2 amplitude and the amplitude of a late ERP component between 400 and 600 ms. Interestingly, the P3 amplitude of the auditory oddball response was not correlated with accuracy.

Conclusions

Event-related potentials recorded during a standard auditory oddball session moderately predict aptitude in an audiory and highly in a visual P300 BCI. The predictor will allow for faster paradigm selection.

Significance

Our method will reduce strain on patients because unsuccessful training may be avoided, provided the results can be generalized to the patient population.     

The sensitivity of human event-related potentials and reaction time to mobile phone emitted electromagnetic fields

There is some evidence to suggest that exposure to mobile phones (MPs) can affect neural activity, particularly in response to auditory stimuli. The current investigation (n = 120) aimed to test recent findings in this area, namely that N100 amplitude and latency would decrease, and that P300 latency and reaction time (RT) would increase under active relative to sham exposure during an auditory task. Visual measures were also explored. A double blind, counterbalanced, crossover design was employed where subjects attended two sessions 1 week apart. In both sessions participants (1) performed auditory and visual oddball tasks while electroencephalogram (EEG) was recorded with a MP set to sham exposure mounted over the temporal region, and (2) performed the same tasks while the handset was set to active/sham. When active, the MP transmitted for 30 min at 895 MHz (average power 250 mW, pulse modulated at 217 Hz, average SAR 0.11 W/kg). Paired t-tests compared difference scores from the sham/sham session to those from the sham/active condition. The study was designed to detect differences of 1\4 of a standard deviation with a power of 0.80. There was no significant difference between exposure conditions for any auditory or visual event related potential (ERP) component or RT. As previous positive findings were not replicated, it was concluded that there is currently no evidence that acute MP exposure affects these indices of brain activity.     

Express Attentional Re-Engagement but Delayed Entry into Consciousness Following Invalid Spatial Cues in Visual Search

Background

In predictive spatial cueing studies, reaction times (RT) are shorter for targets appearing at cued locations (valid trials) than at other locations (invalid trials). An increase in the amplitude of early P1 and/or N1 event-related potential (ERP) components is also present for items appearing at cued locations, reflecting early attentional sensory gain control mechanisms. However, it is still unknown at which stage in the processing stream these early amplitude effects are translated into latency effects.

Methodology/Principal Findings

Here, we measured the latency of two ERP components, the N2pc and the sustained posterior contralateral negativity (SPCN), to evaluate whether visual selection (as indexed by the N2pc) and visual-short term memory processes (as indexed by the SPCN) are delayed in invalid trials compared to valid trials. The P1 was larger contralateral to the cued side, indicating that attention was deployed to the cued location prior to the target onset. Despite these early amplitude effects, the N2pc onset latency was unaffected by cue validity, indicating an express, quasi-instantaneous re-engagement of attention in invalid trials. In contrast, latency effects were observed for the SPCN, and these were correlated to the RT effect.

Conclusions/Significance

Results show that latency differences that could explain the RT cueing effects must occur after visual selection processes giving rise to the N2pc, but at or before transfer in visual short-term memory, as reflected by the SPCN, at least in discrimination tasks in which the target is presented concurrently with at least one distractor. Given that the SPCN was previously associated to conscious report, these results further show that entry into consciousness is delayed following invalid cues.     

Clinical and neuroimaging correlates of abnormal short-latency Somatosensory Evoked Potentials in elderly vascular dementia patients: A psychophysiological exploratory study

BACKGROUND: Short Latency Somatosensory Evoked Potentials (SEPs) may serve to the testing of the somatosensory tract function, which is vulnerable and affected in vascular encephalopathy. The aim of the current study was to search for clinical and neuroimaging correlates of abnormal SEPs in vascular dementia (VD) patients. MATERIALS AND METHODS: The study included 14 VD patients, aged 72.93 PlusMinus; 4.73 years, and 10 controls aged 71.20 PlusMinus; 4.44 years. All subjects underwent a detailed clinical examination, blood and biochemical testing, brain MRI and were assessed with the MMSE. SEPs were recorded after stimulation from upper and lower limbs. The statistical Analysis included 1 and 2-way MANCOVAs and Factor analysis RESULTS: The N13 latency was significantly prolonged, the N19 amplitude was lower, the P27 amplitude was lower and the N11-P27 conduction time was prolonged in severely demented patients in comparison to controls. The N19 latency was prolonged in severely demented patients in comparison to both mildly demented and controls. The same was true for the N13-N19 conduction time, and for the P27 latency. Patients with subcortical lesions had all their latencies prolonged and lower P27 amplitude. DISCUSSION: The results of the current study suggest that there are significant differences between patients suffering from VD and healthy controls in SEPs, but these are detectable only when dementia is severe or there are lesions located in the subcortical regions. The results of the current study locate the abnormal SEPs in the white matter, and are in accord with the literature.     

Dancers and fastball sports athletes have different spatial visual attention styles

Physical exercise and the training effects of repeated practice of skills over an extended period of time may have additive effects on brain networks and functions. Various motor skills and attentional styles can be developed by athletes engaged in different sports. In this study, the effects of fast ball sports and dance training on attention were investigated by event related potentials (ERP). ERP were recorded in auditory and visual tasks in professional dancer, professional fast ball sports athlete (FBSA) and healthy control volunteer groups consisting of twelve subjects each. In the auditory task both dancer and FBSA groups have faster N200 (N2) and P300 (P3) latencies than the controls. In the visual task FBSA have faster latencies of P3 than the dancers and controls. They also have higher P100 (P1) amplitudes to non-target stimuli than the dancers and controls. On the other hand, dancers have faster latencies of P1 and higher N100 (N1) amplitude to non-target stimuli and they also have higher P3 amplitudes than the FBSA and controls. Overall exercise has positive effects on cognitive processing speed as reflected on the faster auditory N2 and P3 latencies. However, FBSA and dancers differed on attentional styles in the visual task. Dancers displayed predominantly endogenous/top down features reflected by increased N1 and P3 amplitudes, decreased P1 amplitude and shorter P1 latency. On the other hand, FBSA showed predominantly exogenous/bottom up processes revealed by increased P1 amplitude. The controls were in between the two groups.     

Pain-related and cognitive components of somatosensory evoked potentials following CO2 laser stimulation in man

We recorded cortical potentials evoked by painful CO₂ laser stimulation (pain SEP), employing an oddball paradigm in an effort to demonstrate event-related potentials (ERP) associated with pain. In 12 healthy subjects, frequent (standard) pain stimuli (probability 0.8) were delivered to one side of the dorsum of the left hand while rare (target) pain stimuli (probability 0.2) were delivered to the other side of the same hand. Subjects were instructed to perform either a mental count or button press in response to the target stimuli. Two early components (N2 and P2) of the pain SEP demonstrated a Cz maximal distribution, and showed no difference in latency, amplitude or scalp topography between the oddball conditions or between response tasks. In addition, another positive component (P3) following the P2 was recorded maximally at Pz only in response to the target stimuli with a peak latency of 593 msec for the count task and 560 msec for the button press task. Its scalp topography was the same as that for electric and auditory P3. The longer latency of pain P3 can be explained not only by its slower impulse conduction but also by the effects of task difficulty in the oddball paradigm employing the pain stimulus compared with electric and auditory stimulus paradigms. It is concluded that the P3 for the pain modality is mainly related to a cognitive process and corresponds to the P3 of electric and auditory evoked responses, whereas both N2 and P2 are mainly pain-related components.     

P 300 latency, age and cognitive styles

20 normal subjects were submitted to seven auditory ERP paradigms in which they were required to count regularly presented cliks (A1, A2, A3), cliks presented in pseudorandom order (B) and in which they had to discriminate relevant from non relevant stimuli characterized by side of provenience (C1, C2) or intensity difference (D). In paradigms C and D a P 300 component was evoked. Age was significantly correlated with P 300 latency only in paradigm D. There was a significant relationship between differences in subjective feelings of difficulty or engagement in performing the counting tasks in C and D and P 300 latency.     

Task difficulty,probability, and inter-stimulus interval as determinants of P300 from auditory stimuli

The P300 event-related potential was elicited with auditory stimuli in 4 experiments which manipulated combinations of stimulus target probability (10% vs. 30%), task difficulty (easy vs. hard), and inter-stimulus interval (5 sec vs. 2 sec). P300 amplitude was smaller and peak latency longer for the more difficult relative to the easier tasks across experiments. Increases in stimulus target probability generally diminished P300 amplitude and shortened peak latency more for the easy relative to difficult task conditions. Increasing the number of non-target stimulus tones decreased P300 amplitude reliably, but increased latency only slightly. Task difficulty did not interact with variations in inter-stimulus interval which produced generally weak effects for both amplitude and latency. These findings suggests that P300 amplitude and latency obtained from auditory discrimination paradigms reflect processing difficulty independently of stimulus target probability unless differences in task requirements affect stimulus encoding.     

Auditory event-related potentials in well-characterized groups of children

Sixty-eight subjects ranging in age from 6 to 23 years were studied in an ‘auditory oddball’ event-related potential (ERP) paradigm. Our results replicate other studies, finding P3 as the most consistent component of ERPs since childhood, although great variability of this component was found in the 6-year-old group. Separate age/ERP component latency and amplitude linear regressions were computed for subjects 6–14 and 6–23 years old. Our data show in both groups a significant negative and positive correlation between age and P3 latency and N1-P2 amplitude respectively. The age/P3 latency slope for the subjects under 15 years old was −19.00 msec/year versus 8.15 msec/year for all subjects (6–23 years old). Our results indicate that P3 latency during childhood decreases with age, reaching an asymptote after or during the second decade of life. No curvilinear relationship between age and P3 latency was found over the child groups, although a significant curvilinear relationship was found over the entire age range.This study showed no significant gender differences in latency at any age group. However, in the adult group females showed significantly larger amplitudes than males.     

P300 and the menstrual cycle

Event-related potentials (ERPs) were elicited with an auditory discrimination paradigm in 20 adult female subjects on the first day of their menstrual cycles and approximately 14 days later. The amplitude and latency of the N1, P2, N2 and P3 (P300) components were measured for the two assessment times. No differences in either amplitude or latency for any of the components were observed as a function of menstrual cycle. Half the subjects who took oral contraceptives were compared to the other half who did not. No differences or interactions between these subgroups were obtained for any component amplitude or latency. It was concluded that menstrual cycle and use of oral contraceptives do not affect the P3 or other ERP components.     

P300 from a single auditory stimulus

The P3(00) event-related brain potential (ERP) was elicited with auditory stimuli to compare 2 different discrimination tasks. The oddball paradigm presented both target and standard tones; the single-stimulus paradigm presented at target but no standard tone stimulus. Experiment 1 manipulated target stimulus probability (0.20, 0.50, 0.80) and produced highly similar P3 amplitude and latency results across probability levels for each paradigm. Experiment 2 factorially varied inter-stimulus interval (2 sec, 6 sec) and target stimulus probability (0.20, 0.80). P3 amplitude and latency were highly similar for both the oddball and single-stimulus procedures across all conditions.     

Heritable features of the auditory oddball event-related potential: peaks,latencies, morphology and topography

Baseline auditory ERP data from a larger study of the genetic determinants of the response to alcohol were collected from 59 monozygotic (MZ) twin pairs and from 39 same-sex dizygotic (DZ) twin pairs who drank socially. Three methods for measuring genetic influence on the ERPs were applied. First, based on maximum-likelihood estimates, the heritability of conventional peak amplitude and latency of N1 and P3 components was computed for each of 16 lead locations using tests of the significance of heritability based on intraclass correlations. P3 amplitude provided the strongest results, distributed symmetrically over caudal leads, and implied gene dominance as the mode of genetic transmission for the P3 component. A substantial genetic influence on N1 latency suggested a mixture of additive and dominance effects in the left fronto-temporal region. N1 amplitude measures trended towards significant heritability, but none was observed for P3 latency. The second method used the maximum of the cross-correlation function to compare wave form shape in a lead-by-lead analysis of data from cotwins. Genetic influence was apparent in both target and non-target ERP responses, with a fronto-central topography of significant results. The third method reduced all spatial and temporal ERP differences from a pair of twins to a single scalar number for each response. Distributions of this global measure revealed significant genetic influence on both non-target and target ERPs. A post hoc analysis of the effect of gender on the heritability of N1 or P3 peaks and latencies revealed no statistically significant observations in this sample of young adult twins.     

Visual cognitive dysfunction in depression: an event-related potential study

The P3(00) event-related potentials (ERPs) elicited by visual stimuli in two visual tasks were assessed in depressed patients (12 patients with major depression and 11 patients with bipolar disorder) and compared with those of 20 age-matched normal controls. At remission, the ERPs from 18 of the depressed patients were again recorded. The visual oddball (VO) paradigm presented both target and standard visual stimuli and the simple visual (SV) paradigm presented a target but no standard visual stimulus. Subjects performed the VO task significantly less accurately than the SV task, as reflected by the behavioral measures (reaction-time and task accuracy). Depressed patients of the bipolar group showed longer P3 peak latency for the VO task and no change in P3 amplitude. No significant differences were found in any other ERP component between the groups. During remission, slowing RTs and reduced P3 peak latencies were observed for both major depression and bipolar disorder groups. Thus, the P3 ERP may be an index of the contribution of the slowed central processing to psychomotor retardation in clinically homogenous samples of depressive patients performing an appropriately demanding task.     

P300 from a single-stimulus paradigm: passive versus active tasks and stimulus modality

The P300 component of the event-related brain potential (ERP) was elicited with auditory and visual stimuli in separate experiments. Each study compared an oddball paradigm that presented both target and standard stimuli with a single-stimulus paradigm that presented a target but no standard stimuli. Subjects were instructed in different conditions either to ignore the stimuli, press a response key to the target, or maintain a mental count of the targets. For the passive ignore conditions, P300 amplitude from the single-stimulus paradigm was larger than that from the oddball paradigm. For the active tasks, P300 amplitude from the oddball paradigm was larger than that from the single-stimulus paradigm. For the press and count conditions, P300 amplitude and latency were highly similar for the oddball and single-stimulus procedures. The findings suggest that the single-stimulus paradigm can provide reliable cognitive measures in clinical/applied testing for both passive and active response conditions.     

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.     

Effects of aerobic exercise and gender on visual and auditory P300, reaction time, and accuracy

Visual and auditory reaction times (RTs) have been reported to decrease during moderate aerobic exercise, and this has been interpreted as reflecting an exercise-induced activation (EIA) of cognitive information processing. In the present study we examined changes in several independent measures of information processing (RT, accuracy, P300 latency and amplitude) during exercise, and their relationship to visual or auditory modalities and to gender. P300 latencies offer independent measures of cognitive speed that are unrelated to motor output, and P300 amplitudes have been used as measures of attentional allocation. Twenty-four healthy college students [mean (SD) age 20 (2) years] performed auditory and visual "oddball" tasks during resting baseline, aerobic exercise, and recovery periods. Consistent with previous studies, both visual and auditory RTs during exercise were significantly shortened compared to control and recovery periods (which did not differ from each other). We now report that, paralleling the RT changes, auditory and visual P300 latencies decreased during exercise, indicating the occurrence of faster cognitive information processing in both sensory modalities. However, both auditory and visual P300 amplitudes decreased during exercise, suggesting diminished attentional resource allocation. In addition, error rates increased during exercise. Taken together, these results suggest that the enhancement of cognitive information processing speed during moderate aerobic exercise, although operating across genders and sensory modalities, is not a global facilitation of cognition, but is accompanied by decreased attention and increased errors.     

Low-Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) Affects Event-Related Potential Measures of Novelty Processing in Autism

In our previous study on individuals with autism spectrum disorder (ASD) (Sokhadze et al., Appl Psychophysiol Biofeedback 34:37–51, 2009a) we reported abnormalities in the attention-orienting frontal event-related potentials (ERP) and the sustained-attention centro-parietal ERPs in a visual oddball experiment. These results suggest that individuals with autism over-process information needed for the successful differentiation of target and novel stimuli. In the present study we examine the effects of low-frequency, repetitive Transcranial Magnetic Stimulation (rTMS) on novelty processing as well as behavior and social functioning in 13 individuals with ASD. Our hypothesis was that low-frequency rTMS application to dorsolateral prefrontal cortex (DLFPC) would result in an alteration of the cortical excitatory/inhibitory balance through the activation of inhibitory GABAergic double bouquet interneurons. We expected to find post-TMS differences in amplitude and latency of early and late ERP components. The results of our current study validate the use of low-frequency rTMS as a modulatory tool that altered the disrupted ratio of cortical excitation to inhibition in autism. After rTMS the parieto-occipital P50 amplitude decreased to novel distracters but not to targets; also the amplitude and latency to targets increased for the frontal P50 while decreasing to non-target stimuli. Low-frequency rTMS minimized early cortical responses to irrelevant stimuli and increased responses to relevant stimuli. Improved selectivity in early cortical responses lead to better stimulus differentiation at later-stage responses as was made evident by our P3b and P3a component findings. These results indicate a significant change in early, middle-latency and late ERP components at the frontal, centro-parietal, and parieto-occipital regions of interest in response to target and distracter stimuli as a result of rTMS treatment. Overall, our preliminary results show that rTMS may prove to be an important research tool or treatment modality in addressing the stimulus hypersensitivity characteristic of autism spectrum disorders.