Establishment of normal values for flash visual evoked potentials (VEPs) in preterm infants: a longitudinal study with special reference to two components of the N1 wave

To establish normal values for flash visual evoked potentials WEN in the preterm period, we analyzed 356 records from 63 neurologically normal infants (26–35 weeks gestation) followed longitudinally. Using both sleep and drowsy state recording within the same session and a mean of 5.7 weekly recording sessions per infant, we hypothesized that the prominent negative wave (N1) consisted of 2 negative components, Nla (early) and N1b (late). This hypothesis could explain the previously reported variability in VEP indices.With a precise definition of the Nla peak, we were able to establish reference ranges for Nla peak latencies at various postmenstrual ages (PMA) which, unlike those previously reported, are narrow enough to be clinically useful. From a cross-sectional analysis we found that the Nla peak latency decreased with maturation at about 4.6 msec/week between 30 and 40 weeks PMA (P > 0.001).We also analyzed the N1 wave form and demonstrated its developmental maturation during this period. There were significant decreases in the amplitudes of both the Nla and N1b peaks with maturation (P > 0.001), but the decrease of the Nla amplitude was steeper than that of N1b The N1 wave form changed from a wave in which the early peak (Nla) was higher than the late peak (Nlb) into the reverse with N1b higher than Nla. This wave change may be related to developmental processes in the visual system. Longitudinal follow-up revealed that extra-uterine life may accelerate the maturation of the N1 wave form but has no effect on the decrease of the absolute values of peak latencies.     

Developmental wave form analysis of the neonatal flash evoked potential

A multiple regression technique was used to describe the wave form of the flash evoked potential (VEP) in 64 neonates born between 28 and 39 weeks of gestation. The successive appearance of new features in the VEP with increasing gestational age at birth was used to define 5 components, of which specimens were obtained by averaging VEPs of 18 selected infants. The VEPs of the other 46 infants were expressed as linear sums of the components, each multiplied by a weighting coefficient. The method accounted for 74 ± 11% (mean ± 1 S.D.) of the rms power of the observed VEPs and was used to demonstrate significant effects on wave form maturation from fetal growth retardation and maternal smoking in pregnancy.     

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.     

Multimodality evoked potentials as a prognostic tool in term asphyxiated newborns

Hypoxic-ischemic (HI) events may cause permanent brain damage, and it is difficult to predict the long-term neurological outcome of survivors. Multimodality evoked potentials (MEPs), using flash visual (fVEPs), somatosensory (SEPs), and brain-stem auditory evoked potentials (BAEPs) may assess the cerebral function in term neonates. MEPs were recorded in 40 hypoxic-ischemic term or near-term neonates during the first week of life in order to predict the neurological outcome. A 3 point grading system registered either mild, moderate, or severe abnormalities. At 24 months of corrected age, the infants were assessed with a blind protocol to determine neurological development. Grade 0 fVEPs and SEPs were associated with a normal neurological status with 100% (P<0.001) of the infants. Abnormal SEPs or total grade (VEPs+SEPs)>I were not associated with normal outcomes (P<0.0001). Normal BAEPs did not predict a normal outcome, but severely abnormal BAEPs did predict an abnormal outcome. A significant correlation was found between EP (VEPs+SEPs) grade (r=0.9, P<0.0001), Sarnat stage (r=0.6, P<0.001), and clinical outcome. This study confirmed that both fVEPs and SEPs are more accurate as prognostic indicators for term neonates. EPs (VEPs+SEPs) also are more accurate in predicting the ultimate neurological outcome compared with the Sarnat scoring.     

Three-dimensional human pattern visual evoked potentials. II. Multiple sclerosis patients

Pattern visual evoked potentials were obtained from 46 patients with definite relapsing/remitting multiple sclerosis, using both a conventional 5-channel occipital array and a 3-D recording technique consisting of three bipolar derivations approximating the three dimensions of space. These three orthogonal wave forms were displayed as a 3-D Lissajous trajectory for each subject. Two of the 15 patients with completely normal conventional pattern VEPs had abnormalities of the orientation of the B-C curvilinear segment of the 3-D pattern VEPs. Delays in the first major occipital positive component (P100) were evident using both techniques; the correlation between P100 latency and the latency of the corresponding trajectory apex was r = 0.99 (P < 0.01). Post-chiasmal MRI abnormalities were associated with 3-D VEP orientation abnormalities. Three-dimensional pattern VEPs are moderately more sensitive than conventional pattern VEPs at detecting dysfunction posterior to the optic chiasm in demyelinating disease and do not require the use of eccentric fixation to do so.     

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.     

Effects of age and sex on pattern electroretinograms and visual evoked potentials

Pattern-electroretinograms (P-ERGs) and visual evoked potentials (VEPs) were simulataneously recorded in 112 normal individuals aged 20–75. Two sized checks subtending 15′ and 31′ were used as stimuli. A weighted regression analysis was used to determine which of the variables, sex or age, was significant. The latency of the a and b wave of the P-ERGs showed a progressive increase with age but no difference between sexes. The effect was statistically significant for both 15′ and 31′ checks. There was no statistically significant aging effects for VEPs elicited by 31′ checks. Aging, however, affected N70, P100, and the interpeak interval between b wave to N70 and b wave to P100 for responses to 15′ checks. Shorter VEP latencies were noted in females for both 15′ and 31′ checks.The simultaneous recording of P-ERGs and VEPs has demonstrated that aging is a major variable at the retinal level. The effects on the a and b waves are mostly due to optic changes with aging and only partially to aging changes in the neuronal retinal circuitry. The effect of aging on VEPs is different for different size stimuli. The cause is a random neuronal cell loss in the visual pathways from the optic nerve to the visual cortex as the individual ages.The difference in VEP data between sexes may be related to anatomical size and hormonal influences.     

Vitamin C in premature and full-term human neonates

Summary

Plasma concentrations of vitamin C (ascorbic acid, AA) are known to be higher in full-term human neonates than their mothers. Immaturity of placental AA transport could result in low plasma AA concentrations in pre-term infants. We found that plasma AA concentrations in umbilical cord blood of 25 full-term neonates (38–42 weeks gestation) and 33 pre-term neonates (24–36 weeks gestation) were always significantly higher than in the corresponding maternal blood (P < 0.0001). However, plasma AA levels were significantly higher in pre-term than in full-term infants (146 ± 93 vs 102 ± 27 μM, respectively; P = 0.03). Furthermore, a rapid and sharp decrease in plasma AA concentrations from 229 ± 166 μM to 45 ± 18 μM (P < 0.0001) over the first 3 days of life was observed in eight very low birth weight infants (460–1090 g, 24–28 weeks gestation). These findings raise important questions about the in utero functions of AA in the developing fetus and the adequacy of postnatal vitamin C supplementation of the premature infant.     

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.     

SEPs to median nerve stimulation: normative data for paediatrics

Somatosensory evoked potentials (SEPs) provide neurologists with an assessment of the neuraxis from peripheral nerve to sensory cortex. Their value is particularly relevant in paediatric neurology as sensory clinical examination can be difficult in young infants and children. The clinical utility of SEPs, however, requires knowledge of the alterations in wave form which occur with growth and development. This study presents normative SEP data from 4 months-35 years. Different non-linear maturational patterns were seen in spinal and central segments of the nervous system. The cervical components (N12, N13) changed little in latency until 2–3 years, the N20 decreased in latency until 2–3 years and P22 decreased in latency until 6–8 years, after which latencies increased until adulthood. The greatest latency changes occurred in N12 and N13, the least in N20. Wave from morphology and interpeak latencies also changed with age. Adult morphology was achieved early (from 1 year), but central conduction time (N13–N20) reached adult values only at 6–8 years. This study provides normative values of SEPs during maturation and a functional assessment of pathways known to myelinate and mature at varying rates.     

Changes in visual evoked potentials after phosphene electrostimulation in children suffering from myopia

We recorded visual evoked potentials (VEPs) in children suffering from medium and high myopia (3.0 to 6.0 and more than 6.0 D; 28 and 21 patients, respectively); a light flash was used as the stimulus. The VEPs were recorded before and after a curative course of phosphene electrostimulation (PhES; frequency 15 sec⁻¹, 10 to 15 10-min-long everyday sessions). The above course resulted in clear trends toward decreases in the peak latencies of the P60 and P100 VEP components; changes in the latencies of other components were expressed to a lesser extent. In children with medium myopia, the latency of the P60 component decreased, on average, by more than 21% (P < 0.05); in patients with high myopia, the respective decrease was about 12% (P > 0.05). These shifts were accompanied by increases in the mean amplitudes of the P60 and, to a lesser degree, P100 (more expressed in medium myopia). The data obtained allow us to suppose that the PhES course provides increases in the transmission velocity through relay structures of the visual analyzer and in neuronal networks of the visual cortex and also in the number of neuronal units whose activity is reflected in generation of VEPs. Application of the PhES technique is much more effective in relatively moderate myopia. Neirofiziologiya/Neurophysiology, Vol. 40, No. 3, pp. 228–235, May–June, 2008.     

Visual event-related potentials to moving stimuli: normative data

Visual cognitive responses (P300) to moving stimuli were tested in 36 subjects with the aim to find the normal range of P300 parameters. Concomitantly, the circadian intra-individual variability of the P300 was studied in a subgroup of 6 subjects. Visual stimuli consisted of either coherent (frequent stimulus) or non-coherent motion (random stimulus). The oddball paradigm was applied for recording cognitive responses. P300 to rare stimuli had an average latency of 447.3 +/- 46.6 ms and amplitude of 12.9 +/- 6.0 microV. The average reaction time was in the range from 322 to 611 ms and there was no correlation between the reaction time and P300 latency. We did not find any significant circadian changes of the P300 parameters in the 6 subjects tested four times during the same day. Cognitive (event-related) responses (P300) displayed distinctly greater inter-individual variability (S.D. of 50 ms) when compared with pattern-reversal and motion-onset VEPs (S.D. of 6.0 ms and 14 ms, respectively). For this reason, the clinical use of P300 elicited by this kind of visual stimuli seems to be rather restricted and the evaluation of its intra-individual changes is preferable.     

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.     

Scalp-recorded oscillatory potentials evoked by transient pattern-reversal visual stimulation in man

Replicable oscillatory potentials, time-locked to pattern stimuli (9.0° central; counterphase reversal at 2.13 Hz) were dissociated from conventional, broad-band VEPs recorded in healthy volunteers at occipital scalp locations by high-pass digital filtering at 17.0–20.0 Hz. Nine consecutive wavelets were identified with a 56.4 ± 8.4 msec mean latency of the first replicable wavelet and mean peak-to-peak amplitude varying between 0.9 and 2.0 μV. The first 2 wavelets had significantly shorter latencies than wave N70 of unfiltered VEP, whereas the last 2 wavelets had longer latencies than N145. Latency and amplitude values varied as a function of contrast and spatial frequency of the stimulus, with shorter latencies and larger amplitudes at 60–90% contrast level and tuning of amplitude at 5.0 c/deg. All wavelets were correlated with wave P100 of unfiltered VEP, while a correlation with N70 of VEP was observed only for those wavelets with latencies in the range of wave P100. Two patients with documented brain lesions involving the visual system are described as examples of oscillatory responses occurring irrespective of filter bandpass and instead of the expected conventional VEP when the generation of these is interfered with by brain pathology. A substantial cortical contribution to the origin of the oscillatory response is conceivable. It is suggested that the oscillatory response to pattern-reversal stimulation reflects events in the visual system that are parallel to, and partly independent of, the conventional VEP, with potential application in research or for clinical purposes.     

Visual evoked potentials in a patient with prosopagnosia

Visual evoked potentials (VEPs) were recorded from a 53-year-old man with prosopagnosia during presentation of slides of known and unknown faces and under two control conditions. ANOVA comparisons with a normal male group showed no differences in P100 amplitude, P300 amplitude or P300 latency. There were no significant evoked potential differences between the patient and controls specifically related to the face conditions.There was, however, a significant delay in the latency of P100 from both hemispheres during all types of stimuli. This prolonged latency was asymmetrical, showing a right sided emphasis with the control conditions: pattern reversal and slides of geometric designs. This finding, of a dissociation in the interhemispheric delay, provides physiological evidence of stimulus-specific organisation at an early, sensory level.The fact that the P100 component showed a marked delay, yet P300 fell within normal limits for amplitude and latency, suggests that this patient's problem lies at a perceptual level.     

Visual event-related potentials evoked by using a virtual reality display

This study aimed at investigating whether a virtual reality display (VRD) is an appropriate tool for evoking visual event-related potentials (VEPs). VEPs evoked by VRD stimuli were highly similar in form to VEPs evoked by using a computer monitor, both having two dominant peaks, labeled P100 and N200. Monitor and VRD N200 latencies and amplitudes were highly correlated. However, peak latencies were longer and the peaks were broader when stimuli were presented on the VRD. Besides, VRD P100 amplitude was smaller, and an N75 peak could be seen usually only on monitor VEPs.     

Event-related auditory evoked potentials and multiple sclerosis

Long latency event-related auditory evoked potentials, particularly the P300 wave, constitute an objective electrophysiological index of cognitive function. For this reason, these potentials have been studied in a series of 101 patients with multiple sclerosis (MS), classified according to McAlpine's criteria into definite, probable and possible cases. The patients were also classified as depressed or non-depressed according to the DSM-III and Research Diagnostic Criteria. They were also subjected to a battery of psychometric tests.In the patient population the N200 and P300 latencies were increased, as were the P200 latencies, when compared with a control population. This electrophysiological pattern had previously been observed in other conditions characterised by subcortical lesions. Partial correlations (at constant disease duration) between the disability score and the cognitive deficit were found to be significant. Patients with an increased P300 latency had a greater disability and the P300 latency was significantly correlated with the duration of the illness.The N200 and P300 latencies were increased in depressed MS subjects, but this increase did not reach the level of significance. Depression was more frequent in the more severely handicapped patients. This suggests that the origin of the depression seen in multiple sclerosis is only partly organic, and that it is one of the factors contributing to the subcortical cognitive deficit in multiple sclerosis.Progressive forms of the disease exhibited the most profound cognitive deficit, and the most marked increase in P300 latency.     

Postnatal Temporal,Spatial and Modality Tuning of Nociceptive Cutaneous Flexion Reflexes in Human Infants

Cutaneous flexion reflexes are amongst the first behavioural responses to develop and are essential for the protection and survival of the newborn organism. Despite this, there has been no detailed, quantitative study of their maturation in human neonates. Here we use surface electromyographic (EMG) recording of biceps femoris activity in preterm (<37 weeks gestation, GA) and term (≥37 weeks GA) human infants, less than 14 days old, in response to tactile, punctate and clinically required skin-breaking lance stimulation of the heel. We show that all infants display a robust and long duration flexion reflex (>4 seconds) to a single noxious skin lance which decreases significantly with gestational age. This reflex is not restricted to the stimulated limb: heel lance evokes equal ipsilateral and contralateral reflexes in preterm and term infants. We further show that infant flexion withdrawal reflexes are not always nociceptive specific: in 29% of preterm infants, tactile stimulation evokes EMG activity that is indistinguishable from noxious stimulation. In 40% of term infants, tactile responses are also present but significantly smaller than nociceptive reflexes. Infant flexion reflexes are also evoked by application of calibrated punctate von Frey hairs (vFh), 0.8–17.2 g, to the heel. Von Frey hair thresholds increase significantly with gestational age and the magnitude of vFh evoked reflexes are significantly greater in preterm than term infants. Furthermore flexion reflexes in both groups are sensitized by repeated vFh stimulation. Thus human infant flexion reflexes differ in temporal, modality and spatial characteristics from those in adults. Reflex magnitude and tactile sensitivity decreases and nociceptive specificity and spatial organisation increases with gestational age. Strong, relatively non-specific, reflex sensitivity in early life may be important for driving postnatal activity dependent maturation of targeted spinal cord sensory circuits.     

Electrophysiological investigation of the texture discrimination mechanisms

In electrophysiological and psychophysical experiments, we investigated mechanisms of the visual system underlying local and global texture processing. Textures included rectangular matrixes composed of Gabor patches (sine wave grating windowed by a Gaussian envelope). Orientation of each grating varied from 0 to 165 degrees with the step of 15 degrees. Matrixes differed by the amount of Gabor patches with vertical or horizontal orientation. The observers' task was to discriminate the dominant orientation. The advantage of such stimuli involved a possibility to calculate global statistics of the textures, which we considered as the difference between whole amount of vertical and horizontal orientations in the stimulus irrespective of their location. The local statistics was calculated as relative amount of spatially organized nearby gratings (i. e. collinear contours). The subjects' accuracy was low in discriminating less organized textures and gradually improved with the amount of vertically of horizontally oriented Gabor patches, while the reaction time decreased. Visual evoked potentials (VEPs) recorded from occipital lobes revealed different dependencies of their components' magnitude on the amount of equally oriented gratings. Amplitude of the late positive component P3 with latency 400 ms directly depended on the texture discriminability, and N2 wave with latency 180 ms had an S-like dependence. Opposite to that, the magnitude of P2 wave with latency 260 ms was maximal in response to less organized textures and gradually decreased with the amount of equally oriented gratings. The dependencies received were compared with the textures' statistics. Data analysis allowed us to suppose that, in the conditions of our experimental paradigm, two mechanisms were involved in discrimination of the textures--the local and the global processing. We believe that by recording VEPs one can separately investigate activity of these two processes.     

Evoked potential findings in Behçet's disease. Brain-stem auditory,visual, and somatosensory evoked potentials in 44 patients

We studied 54 patients with Behçet's disease, 41 males and 13 females, mean age 28 years. Forty-four patients had auditory brain-stem evoked potential (BAEP) recordings, 39 had pattern reversal visual evoked potentials (VEP), 27 had median nerve somatosensory evoked potential (SEP) recordings, and 25 tibial nerve SEPs. BAEPs were abnormal in 16 patients (52%) with neurological manifestations and in 4 (31%) without, because of decreased amplitude of wave V, prolonged I–III or III–V interpeak latencies, or uncertain/absent waves III and/or V. Eleven patients (40%) with neurological symptoms and 3 patients (25%) without, had abnormal VEPs. Absent potentials, decreased amplitude, with or without prolonged P100 latency, were found in 75% of the cases, the rest had prolonged P100 latency only. Median SEPs were abnormal in 8 patients (38%) with neurological manifestations. Four patients (21%) had abnormal tibial SEPs. Decreased amplitude with or without mild slowing in central conduction was the predominant SEP abnormality. SEPs were normal in all patients without neurological symptoms. In total, 84% of patients with, and 38% of patients without, neurological symptoms had abnormalities of one or more EP modality.When used cautiously, EP studies in Behçet's disease might be helpful to separate neuro-Behçet from other disorders with similar symptomatology, to disclose subclinical CNS involvement, to evaluate and monitor CNS disease activity, and to provide objective measures of treatment response.