Auditory and visual event-related potentials in a controlled investigation of HIV infection

Auditory and visual event-related brain potentials (ERPs) were used to complement neuropsychological and medical assessment in neurologically healthy subjects with asymptomatic and symptomatic human immunodeficiency virus type 1 (HIV-1) infection. Auditory and visual ERPs, recorded using standard oddball paradigms, disclosed delays in late waves (N2 and P3) in symptomatic subjects (CDC stage IV) when compared with matched controls. Abnormally delayed P3 waves in at least one modality were recorded in 41% of symptomatics and this was associated with deficits in neuropsychological performance, particularly psychomotor slowing. However, no differences in late wave latencies between asymptomatic and control subjects were found, though asymptomatics showed delays in auditory N1 and P2 latencies. The number of morphological abnormalities, such as indiscernible late waves as well as topographical variability of the P3 wave, was increased in both HIV seropositive groups and possibly indicates a distinct mechanism of impairment, different from latency delay. Whilst P3 delay in symptomatics was not associated with changes in immune function (T4 cells) there was, however, a link with anaemia and subclinical hepatic dysfunction.     

Developmental changes in P1 and N1 central auditory responses elicited by consonant-vowel syllables

Normal maturation and functioning of the central auditory system affects the development of speech perception and oral language capabilities. This study examined maturation of central auditory pathways as reflected by age-related changes in the P1/N1 components of the auditory evoked potential (AEP). A synthesized consonant-vowel syllable (ba) was used to elicit cortical AEPs in 86 normal children ranging in age from 6 to 15 years and ten normal adults. Distinct age-related changes were observed in the morphology of the AEP waveform. The adult response consists of a prominent negativity (N1) at about 100 ms, preceded by a smaller P1 component at about 50 ms. In contrast, the child response is characterized by a large P1 response at about 100 ms. This wave decreases significantly in latency and amplitude up to about 20 years of age. In children, P1 is followed by a broad negativity at about 200 ms which we term N1b. Many subjects (especially older children) also show an earlier negativity (N1a). Both N1a and N1b latencies decrease significantly with age. Amplitudes of N1a and N1b do not show significant age-related changes. All children have the N1b; however, the frequency of occurrence of N1a increases with age. Data indicate that the child P1 develops systematically into the adult response; however, the relationship of N1a and N1b to the adult N1 is unclear. These results indicate that maturational changes in the central auditory system are complex and extend well into the second decade of life.     

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.     

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.     

Presence of two subcomponents in P9 far-field potential following stimulation of the median nerve

Close scrutiny of scalp recorded P9 far-field potentials following stimulation of the median nerve often revealed dilobed wave forms. We observed that the P9 became 2 distinct peaks (P9a and P9b) when the arm was flexed 90° forward at the shoulder and that it became a pointed single peak with 90–170° lateral abduction of the arm. A simultaneously recorded stationary negative peak (N9), registered over the stimulated arm with the use of a distant reference, also showed similar changes, a dilobed configuration (N9a and N9b) with forward flexion and a single peak with lateral abduction. The latencies of the scalp recorded P9a and P9b and arm recorded N9a and N9b were close but not exactly the same. Nevertheless, the latencies of the scalp-positive and arm-negative peaks shifted in nearly a parallel fashion by changing the arm positions.These findings suggest that the change of axial orientation of the propagating nerve impulse plays an important role for the rise of P9a and that the change of volume geometry surrounding the nerve contributes to the P9b generation. Also, the scalp recorded P9 and arm recorded N9 are one and the same, and oriented with dipole fields extending from the arm, body and to the scalp.     

Auditory event-related potentials in waking infants and adults: a developmental perspective

Auditory event-related potentials (AERPs) were recorded in waking 1 month olds, 3 month olds, 6 month olds and adults in order to study the morphology and development of the wave form in the waking subject. Previous data were generally obtained in sleeping or drowsy infants.The findings indicated that there were 3 quantitative changes in the AERP over the first 6 months of life in waking infants: an increase in the latency of peaks, an increase in peak amplitude, and a decrease in intersubject variability. Adult peak latencies were generally shorter than those for 3 month olds and 6 month olds. Further, latencies ofearlier AERP peaks for 1 and 6 month olds, in the present study, were comparable to those reported in previous investigations with sleeping infants. However, latencies oflater AERP peaks differed from those of previous reports and were closer to those reported for waking adults.With respect to the amplitude, the 6 month olds, in general, had the highest amplitudes, the 1 month olds the lowest, and the 3 month olds and adults fell in between the two groups. Some differences were present between early and late components.The findings of this study are significant in that the AERPs were quantitatively different from those reported in earlier work with sleeping or drowsy infants. If cognitive and perceptual development is to be studied, it is necessary to obtain data on waking subjects. The data presented in this report are consistent with behavioral studies of biobehavioral shifts that are associated with changes in responsivity of the organism to stimuli during the first 6 months of life.     

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.     

Developmental Stage-Specific Hepatocytes Induce Maturation of HepG2 Cells by Rebuilding the Regulatory Circuit

On the basis of their characteristics, we presume that developmental stage-specific hepatocytes should have the ability to induce maturation of hepatoma cells. A regulatory circuit formed by hepatocyte nuclear factor (HNF)-4α, HNF-1α, HNF-6 and the upstream stimulatory factor (USF-1) play a key role in the maturation of embryonic hepatocytes; however, it is unclear whether the regulatory circuit mediates the embryonic induction of hepatoma cell maturation. In this study, 12.5-d to 15.5-d mouse embryonic hepatocytes or their medium were used to coculture or treat HepG2 cells, and the induced maturation was evaluated in vitro and in vivo. In the induced HepG2 cells, the components of the regulatory circuit were detected, their cross-regulation was evaluated and HNF-4α RNA interference was performed. We found that 13.5-d to 14.5-d embryonic hepatocytes could induce HepG2 cell maturation, demonstrated by morphological changes, increased maturation markers and decreased c-Myc and α-fetoprotein (AFP) in vitro. The majority of HepG2 tumors were eliminated by 13.5-d embryonic induction in vivo. All components of the regulatory circuit were upregulated and the binding of HNF-4α, HNF-1α, HNF-6 and USF-1 to their target sites was promoted to rebuild the regulatory circuit in the induced HepG2 cells. Moreover, RNA interference targeting HNF-4α, which is the core of the regulatory circuit, attenuated the induced maturation of HepG2 cells with downregulation of the regulatory circuit. These results revealed that developmental stage-specific hepatocytes could induce the maturation of HepG2 cells by rebuilding the regulatory circuit.     

Brain-stem auditory evoked potentials in the common marmoset (Callithrix jacchus)

Brain-stem auditory evoked potentials (BAEPs) were recorded in 10 common marmosets (Callithrix jacchus) to investigate the effects of recording electrode configurations, stimulus rate, and stimulus frequency on BAEP wave forms and peak latencies. Tone burst stimulations were used to evaluate the effects of pure tone on BAEP wave forms. Five positive peaks superimposed on positive and negative slow potentials were identified in the BAEP recorded at the linkage between the vertex and the dorsal base of the ear ipsilateral to a monaural stimulus. When the reference electrode was placed at the ipsilateral mastoid or the neck, the amplitudes of positive and negative slow potentials and the incidence of wave I increased. There were no significant changes in peak latencies of BAEP waves with changes in stimulus rate from 5 to 20/s. It was possible to record the BAEPs in response to tone burst stimulations at frequencies extending from 0.5 to 99 kHz. Wave I appeared apparently at high stimulus frequencies; while waves III to V, at low frequencies. Wave II was recorded at frequencies ranging from 0.5 to 99 kHz and comprised a superposition of 2 or 3 potentials.     

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.     

Neural correlate of filtering of irrelevant information from visual working memory

In a dynamic environment stimulus task relevancy could be altered through time and it is not always possible to dissociate relevant and irrelevant objects from the very first moment they come to our sight. In such conditions, subjects need to retain maximum possible information in their WM until it is clear which items should be eliminated from WM to free attention and memory resources. Here, we examined the neural basis of irrelevant information filtering from WM by recording human ERP during a visual change detection task in which the stimulus irrelevancy was revealed in a later stage of the task forcing the subjects to keep all of the information in WM until test object set was presented. Assessing subjects' behaviour we found that subjects' RT was highly correlated with the number of irrelevant objects and not the relevant one, pointing to the notion that filtering, and not selection, process was used to handle the distracting effect of irrelevant objects. In addition we found that frontal N150 and parietal N200 peak latencies increased systematically as the amount of irrelevancy load increased. Interestingly, the peak latency of parietal N200, and not frontal N150, better correlated with subjects' RT. The difference between frontal N150 and parietal N200 peak latencies varied with the amount of irrelevancy load suggesting that functional connectivity between modules underlying fronto-parietal potentials vary concomitant with the irrelevancy load. These findings suggest the existence of two neural modules, responsible for irrelevant objects elimination, whose activity latency and functional connectivity depend on the number of irrelevant object.     

Developmental Changes in ERP Responses to Spatial Frequencies

Social interaction starts with perception of other persons. One of the first steps in perception is processing of basic information such as spatial frequencies (SF), which represent details and global information. However, although behavioural perception of SF is well investigated, the developmental trajectory of the temporal characteristics of SF processing is not yet well understood. The speed of processing of this basic visual information is crucial, as it determines the speed and possibly accuracy of subsequent visual and social processes. The current study investigated developmental changes in the temporal characteristics of selective processing of high SF (HSF; details) versus low SF (LSF; global). To this end, brain activity was measured using EEG in 108 children aged 3–15 years, while HSF or LSF grating stimuli were presented. Interest was in the temporal characteristics of brain activity related to LSF and HSF processing, specifically at early (N80) or later (P1 or N2) peaks in brain activity. Analyses revealed that from 7–8 years onwards HSF but not LSF stimuli evoked an N80 peak. In younger children, aged 3–8 years, the visual manipulation mainly affected the visual N2 peak. Selective processing of HSF versus LSF thus occurs at a rather late time-point (N2 peak) in young children. Although behavioural research previously showed that 3–6 year-olds can perceive detailed information, the current results point out that selective processing of HSF versus LSF is still delayed in these children. The delayed processing in younger children could impede the use of LSF and HSF for emotional face processing. Thus, the current study is a starting point for understanding changes in basic visual processing which underlie social development.     

Event-related Potential Study of Novelty Processing Abnormalities in Autism

To better understand visual processing abnormalities in autism we studied the attention orienting related frontal event potentials (ERP) and the sustained attention related centro-parietal ERPs in a three stimulus oddball experiment. The three stimulus oddball paradigm was aimed to test the hypothesis that individuals with autism abnormally orient their attention to novel distracters as compared to controls. A dense-array 128 channel EGI electroencephalographic (EEG) system was used on 11 high-functioning children and young adults with autism spectrum disorder (ASD) and 11 age-matched, typically developing control subjects. Patients with ASD showed slower reaction times but did not differ in response accuracy. At the anterior (frontal) topography the ASD group showed significantly higher amplitudes and longer latencies of early ERP components (e.g., P100, N100) to novel distracter stimuli in both hemispheres. The ASD group also showed prolonged latencies of late ERP components (e.g., P2a, N200, P3a) to novel distracter stimuli in both hemispheres. However, differences were more profound in the right hemisphere for both early and late ERP components. Our results indicate augmented and prolonged early frontal potentials and a delayed P3a component to novel stimuli, which suggest low selectivity in pre-processing and later-stage under-activation of integrative regions in the prefrontal cortices. Also, at the posterior (centro-parietal) topography the ASD group showed significantly prolonged N100 latencies and reduced amplitudes of the N2b component to target stimuli. In addition, the latency of the P3b component was prolonged to novel distracters in the ASD group. In general, the autistic group showed prolonged latencies to novel stimuli especially in the right hemisphere. These results suggest that individuals with autism over-process information needed for the successful differentiation of target and novel stimuli. We propose the potential application of ERP evaluations in a novelty task as outcome measurements in the biobehavioral treatment (e.g., EEG biofeedback, TMS) of autism.     

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.     

Visual evoked potentials in response to dichoptic presentation of sinusoidal grating and noise background

Dichoptic stimulation was used in comparison of visual evoked potentials (VEPs) with those obtained with monocular stimulation (recordings made from the occipital area). 16 subjects viewed sinusoidal gratings with the right eye while a visual noise was added via a mirror for the left eye. In presence of the noise, amplitude of the early VEP components' N1, P1b, and the late component P2 decreased, P1a is not changed in presence of the noise, and the late negative wave N2 increased for all spatial frequencies. The effect of noise on the amplitude of VEPs obtained for monocular and dichoptic stimulation was similar. The data suggest that external noise is filtered by the V1 cortical neurons--matched filters for the gratings.     

The relationship between the parameters of the early and late oscillations of human cortical evoked potentials and the rhythm of acoustic stimulation]

The amplitudes of all deflections of the slow auditory evoked potential (AEP) regularly decrease in alert subjects with the increase of stimulation rate. As compared with the late deflections (P2N2), the decrease of the amplitude of comparatively early deflections (N1P2) is more pronounced. It is a rather logarithmic, than a linear function of the interstimulus interval. The degree of amplitude diminution of slow AEPs due to a greater stimulation rate depends on the intensity of acoustic stimul: at greater sound intensities the decrease is more pronounced. The higher rates of stimulation produce, along with a decreased amplitude, a shorter peak latencies of all slow AEP deflections (except the peak of deflection P1). In narcotic (chloralhydrate) sleep higher rates of stimulation are not attended with any regular changes in the amplitude and peak latencies of the slow AEP.     

Neuronal pathways for the lingual reflex in the Japanese toad

1. Anuran tongue is controlled by visual stimuli for releasing the prey-catching behavior ('snapping') and also by the intra-oral stimuli for eliciting the lingual reflex. To elucidate the neural mechanisms controlling tongue movements, we analyzed the neuronal pathways from the glossopharyngeal (IX) afferents to the hypoglossal (XII) tongue-muscle motoneurons. 2. Field potentials were recorded from the bulbar dorsal surface over the fasciculus solitarius (fsol) to the electrical stimulation of the ipsilateral IX nerve. They were composed of three successive negative waves: S1, S2 and N wave. The S1 and S2 waves followed successive stimuli applied at short intervals (10 ms or less), whereas the N wave was strongly suppressed at intervals shorter than 500 ms. Furthermore, the S1 wave had lower threshold than the S2 wave. 3. Orthodromic action potentials were intra-axonally recorded from IX afferent fibers in the fsol to the ipsilateral IX nerve stimuli. Two peaks found in the latency distribution histogram of these action potentials well coincided with the negative peaks of the S1 and the S2 waves of the simultaneously recorded field potentials. Therefore, the S1 and S2 waves should represent the compound action potentials of two groups of the IX afferent fibers with different conduction velocities. 4. Ipsilateral IX nerve stimuli elicited excitatory postsynaptic potentials (EPSPs) in the tongue-protractor motoneurons (PMNs) and the tongue-retractor motoneurons (RMNs). Inhibitory postsynaptic potentials were not observed. 5. The EPSPs recorded in PMNs had mean onset latencies of 6.4 ms measured from the negative peaks of the S1 wave. The EPSPs were facilitated when paired submaximal stimuli were applied at intervals shorter than 20 ms, but were suppressed at intervals longer than 30 ms. Furthermore, the EPSPs were spatially facilitated when peripherally split two bundles of the IX nerve were simultaneously stimulated. 6. On the other hand, the EPSPs recorded in RMNs had shorter onset latencies, averaging 2.5 ms. In 14 of 43 RMNs, early and late EPSP components could be reliably discriminated. The thresholds for the early EPSP components were as low as those for the S1 waves, whereas for the late EPSP components the thresholds were usually higher than those for the S2 waves.(ABSTRACT TRUNCATED AT 400 WORDS)     

Relation of olfactory event-related potentials to changes in stimulus concentration

Objective: The aim of this study was to investigate the influence of odorant concentration on the olfactory event-related potential (OERP).Design and Methods: OERP were evaluated in 8 men and 8 women (17–34 years of age) in response to 4 concentrations of vanillin (7, 28, 56 and 84% v/v). Sixteen presentations of each concentration (stimulus duration 200 ms, interval 40 s, flow 8 l/min) were applied in a randomized order. EEG recordings were made at 3 midline sites (pos. Fz, Cz, Pz). Amplitudes and latencies of four peaks were measured (latencies in ms at Pz after stimulation with 84% v/v vanillin): P1 (277), N1 (348), P2 (412) and P3 (496). Statistical analysis was performed with MANOVAs (`concentration', `recording site'=within-subject-factors; `age' as covariate).Results: With increasing stimulus concentration amplitudes became significantly larger; this was most pronounced for P3 (P1N1: F=2.90, P<0.05; N1P2: F=5.15, P<0.01; N1P3: F=35.7, P<0.001; P3: F=38.6; P<0.001). Correspondingly, latencies shortened with increasing concentrations (P1: F=25.2; N1: 17.51; P2: 14.8; P3: 13.4; all P<0.001). While there was no correlation between OERP amplitudes and butanol odor detection thresholds, latencies were the shorter the lower the subjects' thresholds (coefficients of correlations for peak latencies at Cz for 84% v/v: P1 r₁₅=minus0.59; N1 r₁₅=minus0.58; P2 r₁₅=minus0.55; P3 r₁₅=minus0.45).Conclusions: The results indicated that both OERP amplitudes and latencies are related to the concentration of olfactory stimuli. They also suggested that latencies exhibit a stronger relation to changes in stimulus intensity compared to OERP amplitudes.