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.     

Age-related changes in pattern visual evoked potentials: differential effects of luminance,contrast and check size

We recorded visual evoked potentials (VEPs) to checkerboard pattern-reversal stimulation in 109 normal subjects (51 males and 59 females; aged 19–84 years) in order to study the aging effect on the multiple channels of the visual system in humans. Transient VEPs to 3 check sizes (15′, 30′ and 50′) were obtained by monocular stimulation. Two test conditions were employed: (1) a high luminance (180 cd/m²) and a low luminance (11 cd/m²) both with a fixed contrast (90%), and (2) a high contrast (85%) and a low contrast (10%) both at a fixed luminance (57 cd/m²). The major features of our results included: (1) the presence of a curvilinear relationship between P100 latency and age for all conditions, while the P100 amplitude did not show any such aging effect, (2) the age-latency function was similar between the two luminance conditions, while it was different between the two contrast conditions, and (3) the differential age effect on the P100 latency caused by changes in contrast depended on the check size. These results suggest that age-related changes in the human visual system are not uniform, but rather are different in the specific functional subdivisions. It is thus hypothesized that aging may differentially influence the separate channels of the human visual system.     

Effect of check size on the pattern reversal visual evoked potential

Modifications of the components of pattern-reversal visual evoked potentials (PR-VEP) with changes in check size of the stimulating pattern were studied in 11 healthy subjects. We made use of 8 different check size ranging between 10 and 90 min of arc. Changes in the check size modified in different manners the latencies and amplitudes of N75, P100 and N145. Two-step statistical analyses using the polynomial regression analysis method revealed significant modifications of latencies of the 3 components, but non-significant modifications of the amplitudes, except for N75. The latency and amplitude of N75 showed a significant inverse linear relationship with the logarithm of the check size, while the P100 and N145 latencies showed significant curvilinear relationships, with minimal latencies at check sizes around 35 min. These findings suggest different physiological properties of N75 from those of P100 and N145, and hence, the necessity to establish normal values for each check size of stimulation, for application in clinical studies.     

Clinical relevance of phase of steady-state VEPs to P100 latency of transient VEPs

Pattern visual evoked potentials (VEPs) to transient and steady-state stimulation were recorded in 10 normal subjects at 4 levels of luminance (180, 57, 22 and 11 cd/m²). VEPs were also recorded in 5 patients with optic neuropathy at a fixed luminance (180 cd/m²). The relationship between P100 latency of transient VEPs (T-VEPs) and the phase of steady-state VEPs (S-VEPs) was analyzed. As luminance decreased in normal subjects, P100 latency was prolonged and the phase lag increased. A significant linear relationship between the P100 latency and phase was found. Patients showed both the prolonged P100 latency and the delayed phase. The simple linear regression line of the phase-P100 latency function of normal subjects closely matched the patients' values. These results suggest that changes in the phase may be equivalent to changes in the P100 latency. S-VEPs, therefore, may be clinically useful in assessing visual function.     

Intracranial recording of short latency somatosensory evoked potentials in man: Identification of origin of each component

In normal subjects the short latency SEPs generally consisted of 3 positive waves (P9, P11, P14) and a succeeding negative wave (N20). To determine the origins of these waves we have made intracranial records from 17 patients, which suggest the following results. P9 originates in stimulated median nerve peripheral to the dorsal roots such as brachial plexus, P11 in the dorsal column of the cervical cord, P14 in the cuneate nucleus and medial lemniscal pathway, and N20 in the cerebral cortex. On the basis of intracranial and intraspinal records, the onset of P11 indicates the arrival of the afferent volley at the cord entry and the peak latency of P11 its arrival time at the C1–2 level dorsal column. The onset latency of P14 indicates the onset of postsynaptic events in cuneate nucleus neurons and the peak latency of P14 arrival at the midbrain.From the ventral surface of the brain-stem 3 positive waves (P′9, P′11, P′14) like the initial positive components of the scalp short latency SEPs (P9, P11, P14) were recorded. The amplitude of P′14 was large compared to that of P14. The peak latencies of P′14 recorded at the medulla and the pons were shorter than that of P14 by 0.7–0.8 msec and 0.2–0.5 msec, respectively. The peak latency of P′14 at the midbrain was almost the same as that of P14. By measuring the distance between the recording electrodes in the brain-stem and the peak latency difference of P′14, the fastest lemniscal conduction velocity was estimated as 56 m/sec.     

Gender factor in longer P100 latency of elderly persons

Monocular pattern-shift visual evoked potentials (PSVEPs) were obtained in 26 neurologically and ophthalmologically normal elderly community volunteers (mean age 59.4, males 15, females 11), and compared with similarly obtained data in 26 sex-matched young subjects (mean age 28.1). Elderly males were age-matched with elderly females, and young males were age-matched with young females. Data analyses at both the midoccipital-linked ears and midoccipital-midcentral derivations revealed that the combined-eye mean P100 latency in the elderly as a whole was significantly longer than the young sex-matched controls (P < 0.02). However, the latency in the elderly males was not significantly different from that of sex-matched young males, or age-matched elderly females. The latency in young female subjects, on the other hand, was significantly shorter both when compared to that of age-matched young males (P < 0.01) and sex-matched elderly females (P < 0.01). The differences in other PSVEP variables, namely, interocular P100 latency differences, P100 amplitudes and interocular P100 amplitude ratios were not significant between the groups and subgroups studied.It is concluded that females account for the major contribution towards the longer P100 latency in the elderly.     

The effect of eccentricity and colour on negativity in pattern onset visual evoked potentials

The effects of stimulus size, eccentricity and colour on the amplitudes of N100 and N130 were investigated in pattern onset VEPs.For black-and-white pattern stimulation, the first set of stimuli was derived from a full dartboard pattern. Central stimulation of various extents was produced by patterns with reduced number of outer rings and for eccentric stimuli a number of central rings were removed from the full pattern. It was found that amplitude of N100 was maximal in VEPs to central stimuli and that it was greatly reduced when eccentric stimulation was applied. The amplitude of N130 showed no significant change in relation to the type of stimulus.When checkerboard stimuli of identical configuration were used for black-and-white pattern stimulation instead of dartboards, systematic changes in peak latencies of N100 were observed in relation to check size. In VEPs to centrally presented small checks the emergence of an early negative peak preceding N100 was recorded at 75 msec. In VEPs to coarse checkerboards presented centrally N100 was often observed with a delayed peak latency of 110 msec. Changes in N130 were not regular when checkerboards with different check sizes were presented centrally. For eccentric checkerboard stimulation, both negative peaks N100 and N130 were revealed. Their peak latencies were similar to those observed in the case of dartboard paracentral stimulation.In VEPs to patterns projected through red or blue filters, regular changes were observed in both negative peaks. Introduction of the red filter led to enhancement of the N100 amplitude in VEPs to dartboard and to checkerboards with fine checks, but it caused no effect on N100 in the VEPs to coarse checkerboards. Introduction of the blue filter led to a decrease in the N100 amplitude in VEPs to dartboard and fine checkerboards and to a slight increase of N100 VEPs to coarse checkerboards. Changes in N130 were observed only when the blue filter was introduced and they corresponded to those which take place when the level of illumination changes from photopic to mesopic.     

Relative value of the inion and mid-parietal locations as additional recording sites in pattern reversal visual evoked potentials

Although the P100 response of pattern reversal visual evoked potentials (PRVEPs) is most commonly recorded from the midline occipital site (MO), the response at this location can occasionally be absent or poorly defined due to anatomical variability of the visual cortex. In these cases, the American Electroencephalographic Society Evoked Potential Guidelines recommends recording from the mid-parietal (MP) and Inion electrode sites. In this study, we compared the amplitude of the P100 component recorded simultaneously from MO, MP and the Inion. PRVEPs obtained following stimulation with 30′ check sizes from 155 consecutive patients (310 eyes) over a 2 year period were analyzed. At each of the 3 recording sites, the peak amplitude of P100 was calculated as N75-P100, P100-N145, and the sum of N75-P100 and P100-N145. There was a statistically significant difference between the electrode sites for all 3 methods of amplitude measurement (one-way ANOVA; P<0.0001). For each method of measurement, there was no significant difference between P100 amplitude at MO or the Inion, but a significantly reduced amplitude at MP compared to both the MO and Inion electrode sites (post hoc Scheffe, P<0.05). The P100 amplitude was highest at the Inion in 18% of responses, including cases where the amplitude at that site was at least twice that at MO. In no case was the amplitude highest at MP. Our results indicate that the Inion is a better recording site compared to MP when acquiring PRVEPs, is often complementary to MO, and should be the first additional site to be used when extra channels are available.     

Scalp potentials following sudden coherence and discoherence of binaural noise and change in the inter-aural time difference: a specific binaural evoked potential or a “mismatch” response?

When uncorrelated random noise signals presented to the two ears suddenly become identical (coherent), a centrally located sound image is abruptly perceived and long latency scalp potentials are evoked. When the same signals are presented monaurally there is no perceived change and no potentials are evoked: hence the response must be purely a function of the binaural interaction.P70, N130 and P220 components were consistently recorded to both coherence and discoherence. N130 was usually largest at Fz and P220 at Cz. No potentials of shorter latency were identified, even after averaging 5000 or more sweeps. When the noise became coherent with an inter-aural time difference (δT) of ±0.5 msec (giving rise to an off-centre sound image), the responses were of slightly longer latency and showed no significant asymmetries between C3 and C4. In binaurally coherent noise, δT changes of ±0.5 or ±1.0 msec evoked similar responses which showed no significant asymmetries on the scalp. N130 was of longer latency when δT was changed from ±0.5 msec to zero, as compared with the converse change.In view of the similarity of all these responses it is considered unlikely that they were due to specific populations of binaurally responsive cortical neurones. The N130 and P220 components are thought to be non-specific potentials which are elicited by amy perceptible change in steady auditory stimulus conditions, due to a “mismatch” between the stimulus and the contents of a short-term auditory memory.     

视力与视觉诱发电位的相关分析

对104例病人的图形翻转VEP的瞬态波形各参数,以及9例正常或近视学生的稳态曲线功率谱与视力之间的关系进行了多元相关统计分析,旨在探讨VEP的哪些参数可客观地评估视力.结果表明,瞬态VEP的波形参数中以13’格诱发的N_1P_1、P_1N_2的峰峰值及P_(100)潜伏期与视力的相关系数最大,故认为,分析视力时以平均P_(100)波的波幅值和P_(100)波潜伏期作指标较为灵敏;而稳态、VEP能谱曲线则显示,视力与平均相叶能谱或刺激频率点的能谱相关性较大,与二次谐波的相关性则小.     

Latency of the P3 event-related potential: Normative aspects and within-subject variability

A growing body of research has focused on the P3 (P300) event-related potential as an electrophysiological correlate of selective attention. The present investigation examines the intrasubject test-retest reliability of the auditory evoked P3 latency measure for neurologically and audiologically normal young adults aged 22–34 years across test sessions separated by 2–4 weeks (N = 9) and across trials within one test session (N = 20). In a target-selection (‘oddball’) paradigm, subjects mentally counted infrequent 2 kHz tone bursts (targets) randomly interspersed within a sequence of 1 kHz tone bursts (non-targets). A strong positive correlation was demonstrated between latencies of test sessions I and II. An analysis of variance did not demonstrate statistically significant latency differences as a function of either tests of trials for the test-retest group (N = 9). Although analysis of variance demonstrated a statistically significant difference between trials within one test session for 20 subjects, the small mean latency difference between trials (4.7 msec) is interpreted as being clinically unimportant. The stability of P3 latency found in this study over a period of 2–4 weeks supports its application to the study of normal and disordered cognitive processes.     

N70 and P100 can be independently affected in multiple sclerosis

We have studied the relationship between N70 and P100 of the pattern visual evoked potential in 98 patients with multiple sclerosis and in 59 controls. In patients with multiple sclerosis, P100 was either absent or had prolonged latency in 121 eyes (61.7%), while N70 was absent or prolonged in 97 eyes (49.5%). The total number of eyes with either N70 and/or P100 abnormalities was 137 (69.9%). Eighty eyes (40.8%) had abnormal latency of both P100 and N70, while 41 eyes showed P100 delays without corresponding N70 changes. Seventeen eyes had abnormal N70, but normal P100 latency. N70 and P100 appear to be more often absent in the definite rather than in the possible multiple sclerosis group. These data show that N70 and P100 can be independently affected in patients with MS.     

Visual evoked potentials in the vicinity of the optic tract during stereotactic pallidotomy

We recorded visual evoked responses in eight patients with Parkinson's disease, using a depth electrode either at or below the stereotactic target in the ventral part of the globus pallidus internus (GPi), which is located immediately dorsal to the optic tract. Simultaneously, scalp visual evoked potentials (VEPs) were also recorded from a mid-occipital electrode with a mid-frontal reference electrode. A black-and-white checkerboard pattern was phase reversed at 1 Hz; check size was 50 min of arc. Pallidal VEPs to full field stimulation showed an initial positive deflection, with a latency of about 50 ms (P50), followed by a negativity with a mean latency of 80 ms (N80). The mean onset latency of P50 was about 30 ms. P50 and N80 were limited to the ventralmost of the GPi and the ansa lenticularis. Left half field stimulation evoked responses in the right ansa lenticularis region while right half field stimulation did not, and vice versa. These potentials thus seemed to originate posterior to the optic chiasm. The scalp VEPs showed typical triphasic wave forms consisting of N75, P100 and N145. The location of the recording electrode in the ansa lenticularis region did not modify the scalp VEP. These results suggest that P50 and N80 are near-field potentials reflecting the compound action potentials from the optic tract. Therefore, N75 of the scalp VEPs may represent an initial response of the striate cortex but not of the lateral geniculate nucleus.     

Short and middle latency vestibular evoked responses to acceleration in man

We have succeeded in recording short and middle latency vestibular evoked responses in human subjects. The head was held rigidly in a special, patented head holder, constructed individually for each subject, which gripped the teeth of the upper jaw. The stimulus consisted of 2/sec steps of angular acceleration impulses produced by a special motor with intensities of about 10,000°/sec² and with a rise time of 1–2 msec. The electrical activity was recorded as the potential difference between special forehead and mastoid electrodes having a large, secure contact area with the skin. The activity was digitally filtered and averaged in 2 separate channels by means of a Microshev 2000 evoked response system. The short latency responses, with peaks at about 3.5 msec (forehead positive), 6.0 msec (forehead negative) and 8.4 msec (forehead positive; bandpass: 200–2000 Hz; average of 1024 trials), had amplitudes of about 0.5 μV. The middle latency responses had peaks at about 8.8 msec (forehead positive), 18.8 msec (forehead negative) and 26.8 msec (forehead positive; 30–300 Hz; N = 128 trials), with larger amplitudes (about 15 μV). These responses were consistently recorded in the same subject at different times and were similar in different normal subjects. Strenuous control experiments were conducted in order to ensure that these responses are not artefacts due to the movement of conducting media (head, electrodes and leads) in the electromagnetic field of the motor and are elicited by activation of normal labyrinths. Among other controls, they were not present in a cadaver, in patients with bilateral absence of nystagmus to caloric stimuli and in conducting volumes the size of the human head. They were also not masked by white noise.     

Brain-stem auditory pathways: effects of atropine]

The efferent pathways exert a control action on the function of the cochlear nucleus and hair cells. Acetylcholine is the neurotransmitter of the centrifugal system and its action can be blocked by Atropine. In order to give a contribution to the knowledge of the function of the efferent bundle, Auditory Brainstem Responses (ABRs) and Acoustic Reflex Latencies (ARLs) have been examined in 10 young normal subjects there was also a decrease in latency greater than or equal to 100 microseconds by at least other two waves. The only statistically significant difference was relative to the latency mean value of the wave III recorded in contralateral derivation at 11 pps. The ARLs, after the infusion of atropine, showed a statistically significant increase in 7 of the 10 cases; no change was recorded in the AR amplitude. It can be concluded that the pharmacological block of the olivo-cochlear bundle determines a delay in the neural conduction of the acoustic impulses; this finding means that the atropine can inhibit the facilitating activity of the efferent system on the brainstem afferent pathways.     

VEP's in normal full-term and premature neonates: longitudinal versus cross-sectional data

VEPs have been shown to change with CNS maturation in children, yet few studies had documented maturational changes in the premature infant. Using LED goggles, VEPs were studied in 75 neurologically normal infants of 22–42 weeks gestational age (GA) within the first 3 days of life. Twenty of these (22–32 weeks GA) were also followed longitudinally.The 22–23 week GA neonates had no identifiable waves. In all infants >24 weeks a large negative wave is seen with a latency around 300 msec (N300). After 27 weeks GA a late positive wave was present (P400), but with more variable latency and morphology. Between 30 and 35 weeks GA a small positive wave (P200) was seen in over one-third of the neonates; this component was present in all infants > 36 weeks GA.The consistency of the N300 across the ages studied suggests that it might arise from the basilar dendrites in the visual cortex, which are well developed by 24 weeks GA and undergo relatively little further development between 24 weeks and term. The P200 is suggested to arise from the apical dendrites which develop in the last trimester, explaining the emergence of P200 after 30 weeks GA.The infants followed longitudinally showed the same components, emerging in the same order, but with more rapid development (particularly of P200) compared to the cross-sectional studies. These data suggest that there are differences in the maturation of the visual system in the extrauterine versus intrauterine environment.     

前部缺血性视神经病变患者图形视觉诱发电位与视功能改变的关系及其临床意义

目的:探究前部缺血性视神经病变(AION)患者图形视觉诱发电位(P-VEP)检查结果与预后间的关系。方法:选择2016年12月-2019年12月于我院就诊并确诊的AION患者作为研究对象,入院后接受综合治疗,治疗后评估患者的视功能,评价患者的治疗效果,采用相关性分析探究患者入院后P-VEP检查结果与经治疗后患者视功能改善值间的相关性。结果:研究组15'棋盘格和60'棋盘格P100波潜伏时均高于对照组,P100波振幅均低于对照组,差异均具有统计学意义(P0.05)。治疗后3个月AION患者最佳矫正视力和视野平均敏感度(MS)高于治疗前,视野平均缺失值(MD)低于治疗前,差异均具有统计学意义(P0.05)。AION患者治疗前后视力差值与15'棋盘格P100波振幅呈正相关,视野MD差值和视野MS差值与P-VEP四项反应值不具有相关性。结论:P-VEP检查结果 15'棋盘格P100波振幅与患者视力改善差值间存在显著的正相关性,可提示患者视功能恢复程度及预后。     

QT interval and QT dispersion before and after diet therapy in patients with simple obesity

To evaluate whether a disordered QT interval and its dispersion in obese patients, if any, may be improved by therapeutic weight reduction, 36 obese patients admitted to our university hospital were examined over a 5-year period from April 1, 1992 to March 31, 1997. Participants included 18 males and 18 females whose mean age +/- SD was 28 +/- 9 and 33 +/- 14 years, respectively, and whose mean body mass index +/- SD was 35 +/- 5 and 38 +/- 6 kg/m2, respectively. Thirty-six control patients were matched in age and gender with the obese patients. All the obese patients were treated with behavioral therapy together with very-low-calorie conventional Japanese diet (VLCD: 370 kcal/day). A standard 12-lead electrocardiogram (ECG) revealed longer maximum (445 +/- 32 msec, mean +/- SD) and minimum (388 +/- 29 msec) heart rate corrected QT intervals (QTc intervals) in the obese group than in the control group (P < 0.0001 for each). QTc dispersion, defined as the difference between maximum and minimum QTc intervals derived from 12-lead ECG, was greater in the obese group (57 +/- 19 msec) than in the control group (32 +/- 13 msec) (P < 0.0001). Both the maximum and minimum QTc intervals in the obese patients were shortened, respectively, to 434 +/- 28 msec and 377 +/- 29 msec (P < 0.05 for each) with no significant change in either QTc dispersion, QRS voltage, or QRS duration following weight reduction. The coefficient value from the linear regression line between QT interval and RR interval in the obese group was less than in the control group. Together, the results show that obesity per se causes both a prolongation of QTc interval and an increase in QTc dispersion, and that weight reduction improves the prolonged QTc interval observed in obese patients.     

Pulmonary gas exchange in humans during exercise at sea level

Previous studies have shown both worsening ventilation-perfusion (VA/Q) relationships and the development of diffusion limitation during exercise at simulated altitude and suggested that similar changes could occur even at sea level. We used the multiple-inert gas-elimination technique to further study gas exchange during exercise in healthy subjects at sea level. Mixed expired and arterial respiratory and inert gas tensions, cardiac output, heart rate, minute ventilation, respiratory rate, and blood temperature were recorded at rest and during steady-state exercise in the following order: rest, minimal exercise (75 W), heavy exercise (300 W), heavy exercise breathing 100% O2, repeat rest, moderate exercise (225 W), and light exercise (150 W). Alveolar-to-arterial O2 tension difference increased linearly with O2 uptake (VO2) (6.1 Torr X min-1 X 1(-1) VO2). This could be fully explained by measured VA/Q inequality at mean VO2 less than 2.5 l X min-1. At higher VO2, the increase in alveolar-to-arterial O2 tension difference could not be explained by VA/Q inequality alone, suggesting the development of diffusion limitation. VA/Q inequality increased significantly during exercise (mean log SD of perfusion increased from 0.28 +/- 0.13 at rest to 0.58 +/- 0.30 at VO2 = 4.0 l X min-1, P less than 0.01). This increase was not reversed by 100% O2 breathing and appeared to persist at least transiently following exercise. These results confirm and extend the earlier suggestions (8, 21) of increasing VA/Q inequality and O2 diffusion limitation during heavy exercise at sea level in normal subjects and demonstrate that these changes are independent of the order of performance of exercise.     

A cladistic and comparative analysis of kinematic components of the fast-start of fishes,with a note on body size constraints

The fast-start is an ecologically relevant behavior pattern in fishes. The present article analyses the distribution of five continuous kinematic traits (latency for response initiation, time to maximum angular velocity, time to maximum displacement velocity, maximum angular velocity, and maximum displacement velocity) in eight of the eleven species described in Eaton (66:65–81, 1977). Phylogenetic generalized least square estimation of ancestor states demonstrated evolutionary changes in maximum angular velocity and maximum displacement velocity, consistent with species differences in the same variables. These changes in maximum velocity are also correlated (phylogenetically independent contrasts) with the mean body sizes of all species, pointing to the possibility that body size was an evolutionary constraint on maximum velocities. The conservation of the other traits suggest that they are mainly constrained by neural control, and a trade-off between neural and body size-constraints is proposed ex hypothesi. An erratum to this article can be found at