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.     

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.     

A subcortical correlate of P300 in man

Event-related potentials in visual and auditory target detection tasks were recorded simultaneously from the scalp, somatosensory thalamus and periaqueductal gray in a chronic pain patient with electrodes implanted subcortically for therapeutic purposes. Short latency tactile responses confirmed the location of the thalamic electrodes.Rare auditory stimuli which were detected by the subject were accompanied by a prominent P300 component at the scalp, and by negative activity at the subcortical sites with the same latency as the scalp positivity. This activity was not seen in responses to frequent non-target stimuli and was not dependent on an overt motor response.Similarly, rare visual stimuli generated a scalp P300 and negative activity subcortically; both scalp and subcortical waves had a longer latency than in the auditory experiment. The reaction time was similarly longer to visual targets.These data are inconsistent with a hippocampal generator for P300, but are consistent with a generator in the thalamus or more dorsally located structures.     

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.     

Diurnal variation in the P300 component of human cognitive event-related potential

Diurnal variation in the P300 component of the human cognitive event-related potential (ERP) was examined. The P300 component is considered to be a measure of neuroelectric activity related to cognitive functions such as attention allocation and information processing. Nine diurnally active healthy male subjects whose sleep-wake rhythms were synchronized prior to the experiment were studied. The P300 components oral temperature, heart rate, left- and right-hand grip strength, reaction time, subjectively rated sleepiness, attention level, and fatigue were measured at 08:00, 11:00, 14:00, 17:00, and 20:00. Significant diurnal variations in P300 latency, P300 amplitude, oral temperature, heart rate, left- and right-hand grip strength, subjectively rated sleepiness, and attention level were observed. The P300 latency at 08:00 was significantly longer than at 11:00, 17:00, and 20:00, while the P300 amplitude at 08:00 was significantly greater than at 17:00 and 20:00. The P300 latency was correlated positively with subjectively rated sleepiness and negatively correlated with subjectively rated attention level. These results suggest the existence of diurnal variation in human cognitive functions.     

Estimate of physiological variability of peak latency in single sweep P300

Among single sweep records of event-related potentials (ERPs), the peak latency of P300, which is one of the most prominent positive peaks in the ERP obtained in the oddball paradigm, may vary depending on the conditions of the subject. In the analysis of characteristics of the variability in the peak latency, it is important to know to what extent the variability of the measured peak latency (measured variability) is actually caused by physiological factors (physiological variability). In our previous study, a method was developed for judging whether the physiological variability really exists or not, and if it does exist, the developed method extracts the physiological variability from the measured variability based on a limited number of single sweep records. In the present study, based on the P300 waveforms which were detected by blinded visual inspection of the ERP data obtained by an auditory oddball paradigm from 12 healthy adults, the physiological variability was shown to exist with a confidence level of 95% for all subjects. Furthermore, its interval estimate was calculated by subtracting noise variability from the measured variability with a confidence level of 80%, and it was found to range from 17 to 57 ms for all subjects.     

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.     

Catecholaminergic function and P300 amplitude in major depressive disorder (P300 and catecholamines)

The neurobiology of P300 is still a subject of controversy. P300 amplitude appears to be modulated by multiple neurotransmitter systems, especially dopaminergic, noradrenergic as well as cholinergic and GABAergic. In this study, we investigated the relationship between P300 amplitude and catecholaminergic neurotransmission as assessed by the growth hormone (GH) response to clonidine and apomorphine challenges in 20 major depressive patients. Results showed a correlation of P300 amplitude with the apomorphine test (r = 0.54; P = 0.01), but not with the clonidine test (r = 0.22; NS). This study supports a role for dopamine in the neurobiological modulation of P300 amplitude.     

DIURNAL VARIATION IN THE P300 COMPONENT OF HUMAN COGNITIVE EVENT-RELATED POTENTIAL

Diurnal variation in the P300 component of the human cognitive event-related potential (ERP) was examined. The P300 component is considered to be a measure of neuroelectric activity related to cognitive functions such as attention allocation and information processing. Nine diurnally active healthy male subjects whose sleep-wake rhythms were synchronized prior to the experiment were studied. The P300 components oral temperature, heart rate, left- and right-hand grip strength, reaction time, subjectively rated sleepiness, attention level, and fatigue were measured at 08:00, 11:00, 14:00, 17:00, and 20:00. Significant diurnal variations in P300 latency, P300 amplitude, oral temperature, heart rate, left- and right-hand grip strength, subjectively rated sleepiness, and attention level were observed. The P300 latency at 08:00 was significantly longer than at 11:00, 17:00, and 20:00, while the P300 amplitude at 08:00 was significantly greater than at 17:00 and 20:00. The P300 latency was correlated positively with subjectively rated sleepiness and negatively correlated with subjectively rated attention level. These results suggest the existence of diurnal variation in human cognitive functions. (Chronobiology International, 17(5), 669–678, 2000)     

Effect of seduksen (diazepam) on cortical P300 potentials evoked by neutral and emotional words

The influence of seduxen (diazepam) on cortical potentials P300 evoked by neutral and emotional words was studied in adult subjects having life conflicts. The therapeutic dose of seduxen (10 mg) had no significant effect on the amplitude of the late positive cortical response P300 to neutral words. Seduxen depresses the emotional activation of the cerebral cortex; that is manifested in selective elimination of those changes in latency and amplitude of P300 wave which are observed in response to emotionally significant words. Under the action of seduxen, the interhemispheric difference in the latency of cortical response disappears due to latency increase in the right hemisphere.     

P300 wave: a comparative study of impulsive aggressive criminals

Event-Related potentials are a simple non-invasive neurophysiological method enabling to comprehend certain aspects of the cognitive processing of information in humans. The best-known component of Event-Related Potentials is the so-called P3 wave. Alterations in the parameters of P300 wave have been discovered in certain personality disorders and in persons with impulsively aggressive behaviour. The purpose of this study is to investigate the changes of these parameters, especially an amplitude and latency in the place of Pz electrode. We examined 15 persons with the impulsive aggressive behaviour and compared them to a population comparable of normal age, gender and approximate degree of education. We used P300 auditory and a neuropsychological Eysenck IVE battery. The results showed that significantly lower amplitudes had been found in the aggressive impulsive subjects as compared to the control group. No statistically significant differences have been discovered in the latency. These results seem to confirm previous studies.     

Changes in P300 following alternate nostril yoga breathing and breath awareness

This study assessed the effect of alternate nostril yoga breathing (nadisuddhi pranayama) on P300 auditory evoked potentials compared to a session of breath awareness of equal duration, in 20 male adult volunteers who had an experience of yoga breathing practices for more than three months. Peak amplitudes and peak latencies of the P300 were assessed before and after the respective sessions. There was a significant increase in the P300 peak amplitudes at Fz, Cz, and Pz and a significant decrease in the peak latency at Fz alone following alternate nostril yoga breathing. Following breath awareness there was a significant increase in the peak amplitude of P300 at Cz. This suggests that alternate nostril yoga breathing positively influences cognitive processes which are required for sustained attention at different scalp sites (frontal, vertex and parietal), whereas breath awareness brings about changes at the vertex alone.     

P300 from a passive auditory paradigm

The P300 (P3) event-related brain potential (ERP) was elicited with a passive tone sequence paradigm and evaluated in 2 studies. Experiment 1 compared ERPs from the passive procedure with those from an active discrimination (oddball) task. The passive sequence paradigm yielded P3 wave forms remarkably similar to those obtained from the active task since both demonstrated central-parietal maximum scalp distributions and virtually identical peak latencies. No differences between tasks were found when ERPs were elicited with subject's eyes open or closed. Experiment 2 compared ERPs from the passive sequence paradigm obtained when subjects were attempting to solve a word puzzle with those from a simple ignore condition. The puzzle-solving secondary task produced a decrease in P3 amplitude relative to the ignore condition, although P3 peak latency was unaffected. These results suggest that the passive sequence paradigm may be a useful and reliable means of eliciting the P3 ERP in subject populations or experimental situations in which an active discrimination task cannot be performed.     

Prolonged P300 latency in children with the D2 dopamine receptor A1 allele.

Previous studies have indicated the presence of a hereditary component in the generation of the P300, or P3, a late positive component of the event-related potential. Moreover, the dopaminergic system has been implicated in the P3. In the present study, 98 healthy Caucasian boys, mean age of 12.5 years and of above-average intelligence, were studied. The sample was composed of 32 sons of active alcoholic (SAA) fathers, 36 sons of recovering alcoholic (SRA) fathers, and 30 sons of social drinker (SSD) fathers, with none of them having yet begun to consume alcohol or other drugs. TaqI A D2 dopamine receptor alleles (A1 and A2) were determined. A significant difference in the frequency of the A1 allele was found among these three groups of boys, with the SAA group having the highest A1 allele frequency (.313), followed by the SRA (.139) and the SSD (.133) groups. The relationship of the A1 and A2 alleles to P3 amplitude and latency was also determined. The results showed no significant difference in P3 amplitude between boys with the A1 and A2 allele. However, P3 latency was significantly longer in the total sample of boys with the A1 allele compared with those carrying the A2 allele. These findings suggest that polymorphism of the D2 dopamine receptor gene is an important determinant of P3 latency.     

Differential changes of laser evoked potentials,late auditory evoked potentials and P300 under morphine in chronic pain patients

The present study investigates the differential behavior of laser evoked brain potentials (LEPs), late auditory evoked potentials (AEP) and the endogenous P300 in response to morphine treatment, examined in 6 chronic pain patients. The main result was that in parallel with marked clinical pain relief, amplitudes of the long latency LEP positivity (P400) were significantly reduced under morphine. One patient suffering from extremely painful osteoporosis for 20 years exhibited a large middle latency component (N170) which was prominently attenuated by morphine. In contrast to LEP amplitude reductions, auditory N1 and P2 potentials appeared either unchanged or even enlarged during morphine treatment. Also P300 amplitude was slightly increased under morphine. Reaction time and mood scales also failed to indicate any sedation. Obviously, LEPs reflected specifically the analgesic morphine effect in this study, while stability or enhancement of AEPs and P300 during morphine treatment indicated lack of sedation or even improved perception and concentration due to the removal of persistent pain as a disruptive perceptual-cognitive stressor.     

P300, stimulus intensity,and modality

Auditory and visual stimulus intensity levels were manipulated systematically in separate conditions to assess the influence of these variables on the P300 event-related brain potential (ERP). Increases in stimulus intensity produced increases in P300 amplitude and decreases in peak latency for both modalities, although the latency effects were stronger for visual stimulation. Similar, somewhat weaker stimulus intensity effects also were observed for the N100, P200, and N200 components. The findings suggest that stimulus intensity contributes to both P300 amplitude and latency measures in important ways and are discussed in relation to the use of ERPs in applied contexts.     

Neuronal Correlates of a Virtual-Reality-Based Passive Sensory P300 Network

P300, a positive event-related potential (ERP) evoked at around 300 ms after stimulus, can be elicited using an active or passive oddball paradigm. Active P300 requires a person’s intentional response, whereas passive P300 does not require an intentional response. Passive P300 has been used in incommunicative patients for consciousness detection and brain computer interface. Active and passive P300 differ in amplitude, but not in latency or scalp distribution. However, no study has addressed the mechanism underlying the production of passive P300. In particular, it remains unclear whether the passive P300 shares an identical active P300 generating network architecture when no response is required. This study aims to explore the hierarchical network of passive sensory P300 production using dynamic causal modelling (DCM) for ERP and a novel virtual reality (VR)-based passive oddball paradigm. Moreover, we investigated the causal relationship of this passive P300 network and the changes in connection strength to address the possible functional roles. A classical ERP analysis was performed to verify that the proposed VR-based game can reliably elicit passive P300. The DCM results suggested that the passive and active P300 share the same parietal-frontal neural network for attentional control and, underlying the passive network, the feed-forward modulation is stronger than the feed-back one. The functional role of this forward modulation may indicate the delivery of sensory information, automatic detection of differences, and stimulus-driven attentional processes involved in performing this passive task. To our best knowledge, this is the first study to address the passive P300 network. The results of this study may provide a reference for future clinical studies on addressing the network alternations under pathological states of incommunicative patients. However, caution is required when comparing patients’ analytic results with this study. For example, the task presented here is not applicable to incommunicative patients.     

Correlations between indices of P300 EEG potential,cognitive tests,and variational pulsometry in Parkinsonian patients

The parameters of an event-related EEG potential (ERP), P300 wave, are now extensively used as objective neurophysiological indices of the state of cognitive functions. At the same time, information on the effects of the autonomic nervous system on the parameters of P300 is limited. In Parkinson’s disease clinics, in addition to the leading motor disorders, more or less clear psychoemotional, cognitive, and autonomic (in particular cardiovascular) impairments are usually observed. This allows one to study the dependence between the cardiovascular dysfunction and intensity of cognitive disorders in Parkinsonian patients. In our study on this contingent, we analyzed correlations between the parameters of P300 potential, indices of the state of the cognitive sphere (determined using a questionnaire, Mini Mental State Examination, MMSE, and a Luriya’s test), and indices of variational pulsometry. Thirty-five Parkinsonian patients (49 to 74 years, severity of disease 1.5 to 3.0 by the international classification) were examined. We found a negative influence of excessive sympathetic tonus in cardiovascular control on the state of cognitive functions. The latency of P300 potential was longer in patients with greater intensities of sympathetic influences on the cardiovascular system. The coefficients of correlation of the latency of P300 with the amplitude of mode of R-R intervals (AMo), index of tension in the regulatory systems by Baevskii (IT), and index of autonomic balance by Baevskii (IAB) were 0.52 (P < 0.01), 0.36 (P < 0.05), and 0.37 (P < 0.05), respectively. The above autonomic indices demonstrated significant negative correlations with the volume of short-term memory measured by Luriya’s test. The P300 latency, in turn, showed negative correlations with the memory volume estimated by the MMSE scale and Luriya’s test. With increase in the age of patients, the degree of the above-mentioned correlations between the P300 latency, memory volume (by Luriya’s test), and parameters of variational pulsometry increased. Our data emphasize the expedience of “routine” studies of the balance of sympathetic and parasympathetic control in pathological states accompanied by clear or subclinical cognitive disorders. Early recognition of cardiovascular dysfunction and its corresponding therapeutic correction should improve the state of brain functions and quality of life in patients suffering from neurodegenerative diseases, in particular from Parkinson’s disease. Neirofiziologiya/Neurophysiology, Vol. 40, No. 1, pp. 43–52, January–February, 2008.     

Interaction of oddball probability and primary task type on P300 in the dual-task paradigm

Using a dual-task paradigm with an oddball secondary task, P300 amplitude and latency were studied as a function of factorially manipulated oddball probability (low = .22, high = .44) and primary task type. In addition to a Baselinecondition (oddball task only), three primary tasks were used: (1) Pure Sensory;watching a movie; (2) Pure Motor (manipulating a flashlight); and (3) Sensory/Motor(using the flashlight to trace the outlines of characters in a movie). The findings included the usual significant effects of probability on amplitude. There was also a significant effect of task type on amplitude, and a significant interaction of oddball probability with task type. In the low but not high probability condition, a pure Sensory task depressed P300 amplitude. In both probability conditions, the Sensory/motortask depressed P300 amplitude. Only task type had a significant effect on P300 latency. The results confirm the ability of other labs (using Sensory/motor primary tasks) to demonstrate P300 depression at high oddball probability, in view of the difficulty in our lab of achieving P300 depression with pure sensory tasks and high oddball probabilities. The results are discussed in terms of partial overlap of processing resource pools. A preliminary report of these data was presented at the 1990 meetings of the Society for Psychophysiological Research.     

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.