Electrophysiological Evidences of Visual Field Alterations in Children Exposed to Vigabatrin Early in Life.

BACKGROUND: We assessed central and peripheral visual field processing in children with epilepsy who were exposed to vigabatrin during infancy. METHODS: Steady-state visual evoked potentials and pattern electroretinograms to field-specific radial checkerboards flickering at two cycle frequencies (7.5 and 6 Hz for central and peripheral stimulations, respectively) were recorded from Oz and at the eye in seven school-age children (10.1 ± 3.5 years) exposed to vigabatrin early in life, compared with children early exposed to other antiepileptic drugs (n = 9) and healthy children (n = 8). The stimulation was made of two concentric circles (0 to 5 and 30 to 60 degrees of angle) and presented at four contrast levels (96%, 64%, 32%, and 16%). RESULTS: Ocular responses were similar in all groups for central but not for the peripheral stimulations, which were significantly lower in the vigabatrin-exposed group at high contrast level. This peripheral retinal response was negatively correlated to vigabatrin exposure duration. Cortical responses to central stimulations, including contrast response functions in the children with epilepsy in both groups, were lower than those in normally developing children. CONCLUSIONS: Alteration of ocular processing was found only in the vigabatrin-exposed children. Central cortical processing, however, was impaired in both epileptic groups, with more pronounced effects in vigabatrin-exposed children. Our study suggests that asymptomatic long-term visual toxicity may still be present at school age, even several years after discontinuation of drug therapy.

Early electrophysiological markers of atypical language processing in prematurely born infants.

Because nervous system development may be affected by prematurity, many prematurely born children present language or cognitive disorders at school age. The goal of this study is to investigate whether these impairments can be identified early in life using electrophysiological auditory event-related potentials (AERPs) and mismatch negativity (MMN). Brain responses to speech and non-speech stimuli were assessed in prematurely born children to identify early electrophysiological markers of language and cognitive impairments. Participants were 74 children (41 full-term, 33 preterm) aged 3, 12, and 36 months. Pre-attentional auditory responses (MMN and AERPs) were assessed using an oddball paradigm, with speech and non-speech stimuli presented in counterbalanced order between participants. Language and cognitive development were assessed using the Bayley Scale of Infant Development, Third Edition (BSID-III). Results show that preterms as young as 3 months old had delayed MMN response to speech stimuli compared to full-terms. A significant negative correlation was also found between MMN latency to speech sounds and the BSID-III expressive language subscale. However, no significant differences between full-terms and preterms were found for the MMN to non-speech stimuli, suggesting preserved pre-attentional auditory discrimination abilities in these children. Identification of early electrophysiological markers for delayed language development could facilitate timely interventions.

Delayed early primary visual pathway development in premature infants: high density electrophysiological evidence.

In the past decades, multiple studies have been interested in developmental patterns of the visual system in healthy infants. During the first year of life, differential maturational changes have been observed between the Magnocellular (P) and the Parvocellular (P) visual pathways. However, few studies investigated P and M system development in infants born prematurely. The aim of the present study was to characterize P and M system maturational differences between healthy preterm and fullterm infants through a critical period of visual maturation: the first year of life. Using a cross-sectional design, high-density electroencephalogram (EEG) was recorded in 31 healthy preterms and 41 fullterm infants of 3, 6, or 12 months (corrected age for premature babies). Three visual stimulations varying in contrast and spatial frequency were presented to stimulate preferentially the M pathway, the P pathway, or both systems simultaneously during EEG recordings. Results from early visual evoked potentials in response to the stimulation that activates simultaneously both systems revealed longer N1 latencies and smaller P1 amplitudes in preterm infants compared to fullterms. Moreover, preterms showed longer N1 and P1 latencies in response to stimuli assessing the M pathway at 3 months. No differences between preterms and fullterms were found when using the preferential P system stimulation. In order to identify the cerebral generator of each visual response, distributed source analyses were computed in 12-month-old infants using LORETA. Source analysis demonstrated an activation of the parietal dorsal region in fullterm infants, in response to the preferential M pathway, which was not seen in the preterms. Overall, these findings suggest that the Magnocellular pathway development is affected in premature infants. Although our VEP results suggest that premature children overcome, at least partially, the visual developmental delay with time, source analyses reveal abnormal brain activation of the Magnocellular pathway at 12 months of age.

A frequency-tagging electrophysiological method to identify central and peripheral visual field deficits.

BACKGROUND: The aim of this study was to develop a fast and efficient electrophysiological protocol to examine the visual field's integrity, which would be useful in pediatric testing. METHODS: Steady-state visual-evoked potentials (ssVEPs) to field-specific radial checkerboards flickering at two cycle frequencies (7.5 and 6 Hz for central and peripheral stimulations, respectively) recorded at Oz were collected from 22 participants from 5 to 34 years old and from 5 visually impaired adolescents (12-16 years old). Responses from additional leads (POz, O1, O2), and the impact of gaze deviation on the signals, were also investigated in a subgroup of participants. RESULTS: Steady-state visual-evoked potentials responses were similar at all electrode sites, although the signal from the central stimulation was significantly higher at Oz and was highly sensitive in detecting gaze deviation. No effect of age or sex was found, indicating similar ssVEP responses between adults and healthy children. Visual acuity was related to the central signal when comparing healthy participants with four central visual impaired adolescents. Clinical validation of our electrophysiological protocol was also achieved in a 15-year-old adolescent with a severe peripheral visual deficit, as assessed with Goldmann perimetry. CONCLUSIONS: A single electrode over Oz is sufficient to gather both central and peripheral visual signals and also to control for gaze deviation. Our method presents several advantages in evaluating visual fields integrity, as it is fast, reliable, and efficient, and applicable in children as young as 5 years old. However, a larger sample of healthy children should be tested to establish clinical norms.

Long-term visual outcome of methylmalonic aciduria and homocystinuria, cobalamin C type.

OBJECTIVE: To describe the long-term ophthalmologic outcomes of patients with methylmalonic aciduria and homocystinuria, cobalamin C type (cblC). DESIGN: Retrospective case series. PARTICIPANTS: All patients with cblC referred to the Department of Ophthalmology of the Centre Hospitalier Universitaire Sainte-Justine from 1984 through 2012 were studied. Twelve such patients were identified. METHODS: Clinical ophthalmic examinations, neuroimaging, electroretinography, and the results of MMACHC mutation analysis were reviewed retrospectively. MAIN OUTCOME MEASURES: We examined visual acuity, ocular alignment, presence of maculopathy and peripheral retinopathy, optic atrophy, and nystagmus. Photopic and scotopic electroretinograms were reviewed. We examined and compared mutations in the MMACHC gene. Neuroimaging abnormalities were compiled when available. RESULTS: Twelve cblC patients were followed up from 2 to 23 years (average, 10 years). Eleven of 12 patients were diagnosed before the age of 1 year (range, birth-2 years). An initial ophthalmic examination was performed within the first year of age in 9 of 12 patients. Visual acuity at the time of presentation was variable, ranging from light perception to 20/20. Visual acuity was worse than 20/100 in 75% (9/12) of patients at last follow-up. Eight patients (67%) had obvious maculopathy on fundus examination. Other findings included peripheral retinopathy (8/12 [67%]), nystagmus (8/12 [67%]), strabismus (5/12 [42%]), and optic atrophy (6/12 [50%]). Funduscopic deterioration was documented in 1 patient, whereas electrophysiologic changes occurred in 4 patients. Neuroimaging results were available in 7 of the patients, revealing corpus callosum atrophy (7/7 [100%]) and periventricular white matter loss (6/7 [85%]). CONCLUSIONS: Most children in our series had early-onset disease with neurologic manifestations and abnormal ophthalmologic examination results. Despite early treatment, many early-onset cblC patients have poor visual function.

Neurophysiological correlates of auditory and language development: a mismatch negativity study.

During child development, physiological changes occur in the auditory cortex, which are reflected by differences in the electrophysiological signals. This study aimed to examine the age-related changes of the Mismatch Negativity component (MMN) in response to speech and non-speech stimuli in a cross-sectional design. Results revealed distinct patterns of activation according to stimulus type and age. Age-related differences for tone discrimination occurred earlier in children's development than did the discriminative process for speech sounds. Therefore, networks involved in speech processing are still immature in late childhood and may be more vulnerable to physiological changes.

Altered EEG spectral activity and attentional behavioral deficits following prolonged febrile seizures: a pilot study.

The consequences of febrile seizures (FSs) in infants are still a matter of debate. It is important to develop non-invasive tools to determine markers of brain function that could have predictive value for the outcome of FSs infants.Pattern visual evoked potentials (pVEPs) were recorded in 18 FS infants (mean age of seizure 15.97 months). Spectral density and coherence analyses were performed in infants evaluated at 1.1 month (n = 4), 5.75 months (n = 4) or 30.33 months (n = 6) following a prolonged FS and compared to age-matched healthy controls. The impact of severity of seizures was assessed by comparing the children who had prolonged FSs to 4 infants that had experienced a simple FS. Cognitive tests (Bayley, Stanford-Binet) were administered at the time of testing in FS and control children. Behavioural measures (Achenbach Child Behavior Check List) were administered two years after the FS. pVEP responses and coherence measures failed to yield significant differences between the FS groups and healthy controls. However, spectral density measures showed a significant increase in delta band activity in both FS groups and a reduced high frequency density only in the prolonged FS groups that was seen up to 39 months post-seizure. Behavioural and cognitive measures revealed cognitive development within average, but lower attentional capacities in the FS infants. The persistent changes in spectral density patterns seen in children with prolonged FS may reflect seizure induced alterations in the developing brain or a result of a complex mode of inheritance. Further studies are needed to determine whether these observations can be used as a marker to predict the vulnerability of the child in developing behavioral deficits or epilepsy.

Development of visual texture segregation during the first year of life: a high-density electrophysiological study.

There are important developmental changes occurring during infancy in visual cortical structures that underlie higher-order perceptual abilities. Using high-density electrophysiological recording techniques, the present study aimed to examine the development of visual mechanisms, during the first year of life, associated with texture segregation. Forty-two normal full term infants were tested at 1, 3, 6 or 12 months of age. Visual-evoked potentials to low-level stimuli varying in orientation (oriVEP) and higher-level textured stimuli (texVEP) were recorded from 128 scalp electrodes. Difference potentials were obtained to extract the VEP component associated specifically with texture segregation (tsVEP). Results show a clear developmental pattern regarding amplitude, latency and scalp distribution of tsVEP, which appears at around 3 months but does not reach maturity by 12 months of age. A reduction in latency is particularly evident between 3 and 6 months, whereas amplitude shows a gradual increase with a marked increment between 3 and 6 months for low-level orientation stimuli and between 6 and 12 months for higher-level textured stimuli. These developmental patterns are attributed to neural maturational processes such as myelination and synaptogenesis. The differential developmental rates can be explained by delayed maturational processes of brain regions involved in more complex visual processing.

Developmental delay and magnocellular visual pathway function in very-low-birthweight preterm infants.

This study investigated the effect of very preterm birth (gestation < or =30wks) and very low birth weight (< or =1500g) on the development of magnocellular and parvocellular visual processing streams. Participants were preterm infants (n=55: 31 females, 24 males) born between 24 and 30 weeks'gestation (mean 27.4wks [SD 1.3]), weighing between 720 and 1470g (mean 1015g [SD 215]) and term infants (n=52: 27 females, 25 males) born between 38 and 42 weeks'gestation (mean 39.4wks [SD 0.9]), weighing between 2670 and 4405g (mean 3549g [SD 440]). Visual-evoked potentials to phase-reversing sine-wave gratings, varying in spatial frequency and contrast, were used to elicit magnocellular and parvocellular specific responses. Previous studies found that the N1 component reflects the parvocellular response, while P1 reflects the magnocellular response in adults and infants. Findings from the current study indicate significantly lower P1 amplitudes in preterm compared with term infants under most conditions. No difference was found for the amplitude of the N1 waveform. Results indicate that, for the age-range tested, preterm birth has little effect on the development of parvocellular function, while it appears to disrupt the development of magnocelluar function.

Alterations of visual evoked potentials in preschool Inuit children exposed to methylmercury and polychlorinated biphenyls from a marine diet.

The aim of the present study was to assess the impact of chronic exposure to polychlorinated biphenyls (PCBs) and methylmercury on visual brain processing in Inuit children from Nunavik (Northern Québec, Canada). Concentrations of total mercury in blood and PCB 153 in plasma had been measured at birth and they were again measured at the time of testing in 102 preschool aged children. Relationships between contaminants and pattern-reversal visual evoked potentials (VEPs) were assessed by multivariate regression analyses, taking into account several potential confounding variables. The possible protective effects of selenium and omega-3 polyunsaturated fatty acids against methylmercury and PCB toxicity were also investigated. Results indicate that exposure to methylmercury and PCBs resulting from fish and sea mammal consumption were associated with alterations of VEP responses, especially for the latency of the N75 and of the P100 components. In contrast, the concomitant intake of omega-3 polyunsaturated fatty acids was associated with a shorter latency of the P100. However, no significant interactions between nutrients and contaminants were found, contradicting the notion that these nutrients could afford protection against environmental neurotoxicants. Interestingly, significant associations were found with concentrations of neurotoxicants in blood samples collected at the time of testing, i.e. at the preschool age. Our findings suggest that VEP can be used as a valuable tool to assess the developmental neurotoxicity of environmental contaminants in fish-eating populations.

Influence of the state of alertness on the pattern visual evoked potentials (PVEP) in very young infant.

The aim of the study was to evaluate the pattern visual evoked potentials (PVEP) combined with an optimal state of vigilance, called liberated state (LS), in order to improve testing in very young infants. Transient PVEP were recorded in response to a checkerboard pattern of 120, 60 and 30 min of arc. in 56 fullterm newborns and 79 preterm infants from birth to 4 months of age. In the fullterms, 28 infants in each group were tested in LS or spontaneous alertness (SA) while in the preterms, 48 infants in each group were tested in LS or SA. No significant difference was found in the amplitude and/or peak time of the PVEP responses between subjects tested in LS compared to SA groups. However, the LS condition improved by approximately 25% the feasibility of prolonged PVEP testing in preterms aged less than 2 months (corrected age). This suggest that the LS condition enhances the clinical feasibility of PVEP testing in very young infants and should be used to optimize the evaluation of visual development in high risk infants in this age group.

Magnocellular and parvocellular developmental course in infants during the first year of life.

The visual system undergoes major modifications during the first year of life. We wanted to examine whether the magnocellular (M) and parvocellular (P) pathways mature at the same rate or if they follow a different developmental course. A previous study carried out in our laboratory had shown that the N1 and P1 components of pattern visual evoked potentials (PVEPs) were preferentially related to the activity of P and M pathways, respectively. In the present study, PVEPs were recorded at Oz in 33 infants aged between 0 and 52 weeks, in response to two spatial frequencies (0.5 and 2.5 c deg(-1)) presented at four contrast levels (4, 12, 28 and 95%). Results indicate that the P1 component appeared before the N1 component in the periods tested and was unambiguously present at birth. The P1 component showed a rapid gain in amplitude in the following months, to reach a ceiling around 4-6 months. Conversely, the N1 component always appeared later and then gained in amplitude until the end of the first year without reaching a plateau. Latencies were also computed but no developmental dissociation was revealed. Results obtained on amplitude are interpreted as demonstrating a developmental dissociation between the underlying M and P pathways, suggesting that the former is functional earlier and matures faster than the latter during the first year of life.