Configural specificity of the lateral occipital cortex.

While regions of the lateral occipital cortex (LOC) are known to be selective for objects relative to feature-matched controls, it is not known what set of cues or configurations are used to promote this selectivity. Many theories of perceptual organization have emphasized the figure-ground relationship as being especially important in object-level processing. In the present work we studied the role of perceptual organization in eliciting visual evoked potentials from the object selective LOC. To do this, we used two-region stimuli in which the regions were modulated at different temporal frequencies and were comprised of either symmetric or asymmetric arrangements. The asymmetric arrangement produced an unambiguous figure-ground relationship consistent with a smaller figure region surrounded by a larger background, while four different symmetric arrangements resulted in ambiguous figure-ground relationships but still possessed strong kinetic boundaries between the regions. The surrounded figure-ground arrangement evoked greater activity in the LOC relative to first-tier visual areas (V1-V3). Response selectivity in the LOC, however, was not present for the four different types of symmetric stimuli. These results suggest that kinetic texture boundaries alone are not sufficient to trigger selective processing in the LOC, but that the spatial configuration of a figure that is surrounded by a larger background is both necessary and sufficient to selectively activate the LOC.

Quantitative fiber tracking of the optic radiation is correlated with visual-evoked potential amplitude in preterm infants.

BACKGROUND AND PURPOSE: Children born preterm are at risk for adverse outcome, including visual impairment. We examined the relationship between neonatal DTI and sVEP in children born preterm to determine whether visual outcomes are related to early measurements of brain microstructure. MATERIALS AND METHODS: Subjects were born at <34 weeks gestation and imaged before term-equivalent age. DTI fiber tracking was used to delineate the optic radiations and measure tract-specific average FA, D(av), and parallel and transverse diffusivity. Visual-evoked response amplitudes were measured as a function of spatial frequency, contrast, and vernier offset size with sVEP at 6-20 months after birth. The association between DTI and sVEP was assessed by using the Spearman correlation coefficient and linear regression for repeated measures. RESULTS: Nine children with 15 scans were included. The peak response amplitudes for spatial frequency sweeps were associated with increasing FA and decreasing D(av) and transverse diffusivity (P ≤ .006) but not with parallel diffusivity (P = 1). There was only modest association with the swept contrast condition and no detectable association with the vernier offset sweeps. CONCLUSIONS: Microstructure of the optic radiations measured shortly after birth is associated with quantitatively measured responses elicited by moderate-to-high contrast spatiotemporal gratings in infancy. These findings are in keeping with studies showing a relationship between brain microstructure and function. While the clinical impact is not known, quantitative neuroimaging of white matter may ultimately be important for predicting outcome in preterm neonates.

Human neutrophil alloantigen-1a, -1b, -2, -3a and -4a frequencies in Brazilians.

Human neutrophil reactive antibodies may cause clinical disorders such as transfusion-related acute lung injury, febrile transfusion reactions, alloimmune neonatal neutropenia, immune neutropenia after stem cell transplantation, refractoriness to granulocyte transfusion, drug-induced neutropenia and autoimmune neutropenia. Using the granulocyte immunofluorescence test by flow cytometry, the phenotypic frequencies of the human neutrophil alloantigens (HNA)-1a, -1b, -2, -3a and -4a were determined in 100 healthy Brazilian persons. Neutrophils were separated from blood samples by sedimentation, centrifugated and incubated with HNA-specific alloantibody plus fluorescein isothiocyanate-labeled F(ab')(2) fragments of anti-human IgG. The results showed that the phenotype frequencies of HNA-1a, -1b, -2a, -3a and -4a were 65%, 83%, 97%, 95% and 94%, respectively. We detected that neutrophils from 17% of Brazilians typed positive only with anti-HNA-1a (HNA-1a/a), 35% only with anti-HNA-1b (HNA-1b/b) and 48% reacted with both antibodies (HNA-1a/b). The frequencies found for HNA-1a and -1b were quite similar to that reported among Africans and American-Africans, but different from those found in Japanese and Chinese. In addition, our data showed that the frequencies of HNA-2, -3a and -4a in Brazilians were comparable with those observed in Caucasians. The determination of HNAs frequencies among populations with distinct racial backgrounds is important not only for anthropological reasons, but also for neonatal typing in suspected cases of alloimmune neutropenia or when patients are severely neutropenic.

Spatio-temporal tuning of coherent motion evoked responses in 4-6 month old infants and adults.

Motion cues provide a rich source of information about translations of the observer through the environment as well as the movements of objects and surfaces. While the direction of motion can be extracted locally these local measurements are, in general, insufficient for determining object and surface motions. To study the development of local and global motion processing mechanisms, we recorded Visual Evoked Potentials (VEPs) in response to dynamic random dot displays that alternated between coherent rotational motion and random motion at 0.8 Hz. We compared the spatio-temporal tuning of the evoked response in 4-6 months old infants to that of adults by recording over a range of dot displacements and temporal update rates. Responses recorded at the frequency of the coherent motion modulation were tuned for displacement at the occipital midline in both adults in infants. Responses at lateral electrodes were tuned for speed in adults, but not in infants. Infant responses were maximal at a larger range of spatial displacement than that of adults. In contrast, responses recorded at the dot-update rate showed a more similar parametric displacement tuning and scalp topography in infants and adults. Taken together, our results suggest that while local motion processing is relatively mature at 4-6 months, global integration mechanisms exhibit significant immaturities at this age.

Development of cortical responses to optic flow.

Humans discriminate approaching objects from receding ones shortly after birth, and optic flow associated with self-motion may activate distinctive brain networks, including the human MT+ complex. We sought evidence for evoked brain activity that distinguished radial motion from other optic flow patterns, such as translation or rotation by recording steady-state visual evoked potentials (ssVEPs), in both adults and 4-6 month-old infants to direction-reversing optic flow patterns. In adults, radial flow evoked distinctive brain responses in both the time and frequency domains. Differences between expansion/contraction and both translation and rotation were especially strong in lateral channels (PO7 and PO8), and there was an asymmetry between responses to expansion and contraction. In contrast, infants' evoked response waveforms to all flow types were equivalent, and showed no evidence of the expansion/contraction asymmetry. Infants' responses were largest and most reliable for the translation patterns in which all dots moved in the same direction. This pattern of response is consistent with an account in which motion processing systems detecting locally uniform motion develop earlier than do systems specializing in complex, globally non-uniform patterns of motion, and with evidence suggesting that motion processing undergoes prolonged postnatal development.

Normalization models applied to orientation masking in the human infant.

Human infants can discriminate the orientation of lines within the first week after birth (Atkinson et al., 1988; Slater et al., 1988) but have immature orientation-selective pattern masking until after 6 months of age (Morrone and Burr, 1986). Here the development of orientation processing is further examined using a visual-evoked potential paradigm and normalization models of pattern masking. Contrast response functions were measured for 1 cycle per degree (cpd) gratings, counterphase-reversed in contrast at either 3.3 or 5.5 Hz. A second 1 cpd, 20% contrast, 8.3 Hz grating of either the same or orthogonal orientation was added as a mask. Evoked responses associated with the test grating, the mask, and intermodulation between the two were individually extracted using spectral analysis of the scalp-recorded EEG. Adults exhibited orientation selectivity in the masking of their test component responses and in nonlinear intermodulation between the test and mask stimuli. Infants <5 months old, however, demonstrated nonselective masking or a reversed selectivity in their responses to the test component, with adult-like orientation selectivity in their intermodulation responses. Within the context of a normalization model of pattern masking, the results are consistent with the existence of oriented filters early in life the responses of which are normalized immaturely until approximately 5 months of age.

Colinear facilitation promotes reliability of single-cell responses in cat striate cortex.

Behavior is controlled by neural activity in the brain. The final outcome of this neural control may critically depend on the firing reliability of individual neurons. A nearly constant, proportional relationship is usually found between the response mean and response variance. Here we asked whether lateral interactions within striate cortex that modulate response magnitude also proportionately modify the response variance of cortical neurons. In many cases, response variability depended on stimulus organization: discrete flankers colinearly placed well outside the neuron's receptive field increased response magnitude without a proportional increase in variance, thus improving the neuron's response reliability. Since colinear flanker facilitation is often seen near the neuron's firing threshold, increased response reliability for weak stimuli may contribute to enhancing perceptual saliency.

Contrast response characteristics of long-range lateral interactions in cat striate cortex.

Single-cell responses in visual cortex to a target falling within their receptive field can be modified by collinear flanking stimuli concurrently presented outside the receptive field. Here, we report the presence of four types of contrast-dependent lateral effects: (1) facilitation at low target contrasts and suppression at high contrasts, (2) facilitation that increases with contrast, (3) suppression that increases with contrast, and (4) suppression at low contrasts with facilitation at high contrasts. We propose a sensitivity modulation model that accounts for all the four types of lateral effects by changes in two parameters. In this model, activation of neighboring neurons changes the sensitivities of the target neuron to both the direct feedforward input and inhibitory, divisive feedback from neighboring neurons.

Contour integration deficits in anisometropic amblyopia.

PURPOSE: Previous retrospective studies have found that integration of orientation information along contours defined by Gabor patches is abnormal in strabismic, but not in anisometropic, amblyopia. This study was conducted to reexamine the question of whether anisometropic amblyopes have contour integration deficits prospectively in an untreated sample, to isolate the effects of the disease from the effects of prior treatment-factors that may have confounded the results in previous retrospective studies. METHODS: Contour detection thresholds, optotype acuity, and stereoacuity were measured in a group of 19 newly diagnosed anisometropic amblyopes before initiation of occlusion therapy. Contour detection thresholds were measured using a card-based procedure. RESULTS: Significant interocular differences in contour detection thresholds were present in 14 of the 19 patients with anisometropic amblyopia. CONCLUSIONS: Contour integration deficits are a common, but not universal, finding in untreated anisometropic amblyopia. Differences in the prevalence of contour integration deficits between the present study and that of another study may lie in differences in treatment history and/or in the sensitivity of the two different contour integration tasks.

Changes in cortical activity during suppression in stereoblindness.

Patients with strabismus or anisometropic amblyopia fixate and attend with one eye and suppress the image from the other eye. Here we use a visual evoked potential technique to show that patients who lack normal stereopsis retain suppressive binocular interactions but lack a characteristic form of non-linear binocular interaction that is present in normal observers. Oscillating grating targets presented at different temporal frequencies in the two eyes evoke a strong response in normal observers at a frequency equal to the sum of the two input frequencies for fusable targets but not for rivalrous ones. However increasing contrast in one eye reduces the response amplitude from the other eye under either fusable (dichoptic masking) or rivalrous conditions. Stereo-deficient observers lack the sum-frequency response, but retain dichoptic masking interactions. Dichoptic masking is stronger when the masker is presented to the patients' dominant rather than non-dominant eyes, suggesting that a subset of preserved binocular inhibitory interactions form the basis of clinical suppression.

A new test of contour integration deficits in patients with a history of disrupted binocular experience during visual development.

Previous studies have suggested that the integration of orientation information across space is impaired in amblyopia. We developed a method for quantifying orientation-domain processing using a test format that is suitable for clinical application. The test comprises a graded series of cards where each card includes a closed path (contour) of high contrast Gabor signals embedded in a random background of Gabor signals. Contour visibility in both normals and patients with histories of abnormal binocular vision depends jointly on the spacing of elements on the contour as well as background element density. Strabismic amblyopes show significant degradation of performance compared to normals. Small but significant losses in sensitivity were also observed in a group of non-amblyopic strabismus patients. Threshold measurements made with contrast reducing diffusers indicated that the amblyopic loss is not due to the reduced contrast sensitivity of the amblyopic eye. An abnormal pattern of long-range connectivity between spatial filters or a loss of such connectivity appears to be the primary source of contour integration deficits in amblyopia and strabismus.

Electrophysiological correlates of vernier and relative motion mechanisms in human visual cortex.

Vernier onset/offset thresholds were measured both psychophysically and with the steady-state VEP by introducing a series of horizontal breaks in a vertical square-wave luminance grating. Several diagnostic tests indicated that the first harmonic component of the evoked response generated by periodic modulation of offset gratings taps mechanisms that encode the relative position of spatial features. In the first test, a first harmonic component was only found with targets that contained transitions between collinear and noncollinear states. VEP vernier onset/offset thresholds obtained with foveal viewing were in the range of 15-22 arc sec. Control experiments with transitions between symmetrical, noncollinear patterns (relative motion) did not produce first harmonic components, nor did full-field motion of a collinear grating. A second series of experiments showed that VEP thresholds based on the first harmonic component of the vernier onset/offset response had an eccentricity dependence that was very similar to that found in a psychophysical discrimination task that required a left/right position judgment (vernier acuity). Other recordings showed that the first harmonic of the vernier onset/offset VEP was degraded by the introduction of a gap between stimulus elements, as is the displacement threshold. The vernier onset/offset target also produced a second harmonic component that was virtually identical to the one produced by a relative motion stimulus. Displacement thresholds based on these second harmonic components showed a more gradual decline with retinal eccentricity than did the first harmonic component elicited by vernier offsets. The second harmonic of the vernier onset/offset VEP was relatively unaffected by the introduction of gaps between the stimulus elements. The first and second harmonic components of the vernier onset/offset VEP thus tap different mechanisms, both of which support displacement thresholds that are finer than the resolution limits set by the spacing of the photoreceptors (hyperacuity).

Development of rivalry and dichoptic masking in human infants.

PURPOSE: To examine the development of rivalry, dichoptic masking, and binocular interactions in infants more than 5 months of age using the visual evoked potential (VEP). METHODS: VEPs were recorded in 35 infants between 5 and 15 months of age and 23 adults between 13 and 59 years of age. Counterphasing, sinusoidal, 1 cycle/deg gratings were presented dichoptically. Responses from each eye were isolated by "tagging" each half-image with a different temporal frequency (5 or 7.5 Hz). Observers were presented with fixed 80% contrast gratings in each eye in experiment 1. Rivalry was detected on the basis of a negative correlation between the simultaneously measured response amplitudes at the second harmonics of the two eye-tagging frequencies. In a second analysis of the same data, response amplitudes recorded under dichoptic viewing conditions were compared to those obtained in a monocular control condition (dichoptic masking). In experiment 2, a 40% fixed-contrast grating was presented to one eye, whereas the other eye viewed a grating that was swept in contrast from 1% to 67%. Dichoptic masking was measured as the reduction in the fixed-grating response caused by the variable contrast grating. RESULTS: Experiment 1: although adults showed evidence of VEP amplitude alternations between the eyes for cross-oriented half-images (physiological rivalry), infants did not. This immature response to rivalrous stimuli occurred despite the presence of responses at nonlinear combination frequencies recorded with gratings of the same orientation in each eye, a definitive indication of binocular interaction. In addition, both iso- and cross-oriented half-images produced less dichoptic masking in infants than in adults in this experiment. Experiment 2: dichoptic masking in the infants was equivalent to that seen in adults with parallel gratings in the two eyes; however, masking with cross-oriented configurations was approximately five times weaker in the infants relative to the adults. CONCLUSIONS: The authors have identified a set of stimulus conditions under which infants between 5 and 15 months of age fail to demonstrate physiological rivalry despite the presence of binocular interactions. The observed lack of binocular rivalry may be the result of a specific immaturity in dichoptic, cross-orientation suppression.

Development of VEP Vernier acuity and grating acuity in human infants.

PURPOSE: To compare the developmental sequences of two basic measures of pattern vision, Vernier acuity and grating acuity, using steady state visual-evoked potentials (VEPs) and an analysis designed to isolate pattern-specific responses from those due to motion in the Vernier stimulus. METHODS: The authors recorded VEPs from 57 healthy full-term infants and 4 adults. The grating acuity stimulus was a sinusoidal grating, temporally modulated (appearance-disappearance) at a rate of 3 Hz, with spatial frequency decreasing in linear steps during each 10-second trial. The Vernier acuity stimulus was a vertical square-wave grating with portions of each bar temporally modulated to make offsets appear and disappear at a rate of 3 Hz. Vernier offset size changed in log steps from small to large offsets. The authors recorded each observer's electroencephalogram (EEG) during multiple presentations of each stimulus type, and the EEG was digitized and filtered to obtain the amplitude and phase of the response at the first two harmonics of the stimulus temporal frequency. Thresholds were estimated with an extrapolation technique that took into account the signal-to-noise ratio and phase of the response. RESULTS: VEP Vernier acuity and grating acuity develop at different rates, with grating acuity approaching adult levels earlier than Vernier acuity. The within-subject relationship between VEP Vernier acuity and grating acuity follows the same developmental trajectory established by previous psychophysical studies of humans and monkeys. CONCLUSIONS: This VEP technique provides a rapid estimate of Vernier acuity in infants. VEP Vernier acuity remains strikingly immature throughout the first year of life, similar to behavioral Vernier acuity. Because Vernier acuity is a sensitive measure of amblyopia, this VEP test may be useful in the future to identify amblyopia and to follow its treatment progress in pediatric patients.

Asymmetric responses in cortical visually evoked potentials to motion are not derived from eye movements.

PURPOSE: Normal neonates and many adults after abnormal visual development have directional preferences for visual stimulus motions; i.e., they give better responses for optokinetic nystagmus (OKN) and visually evoked potentials (VEPs) in one direction than to those in the opposite direction. The authors tested whether the VEP responses were asymmetrical because of abnormal eye movements. METHODS: VEPs were recorded from the visual cortices of five macaque monkeys: one normal, one neonate, and three reared with alternating monocular occlusion (AMO). They were lightly anesthetized, followed by paralysis to prevent eye movements. They then had "jittered" vertical grating patterns presented in their visual fields. The steady state VEPs were analyzed with discrete Fourier transforms to obtain the amplitudes and phases of the asymmetries. RESULTS: The normal, control monkey had small, insignificant amplitudes of its asymmetrical Fourier component and random phases that were not 180 degrees out of phase across the left and right eyes. The neonatal monkey and the AMO monkeys all had large, significant asymmetries that were approximately 180 degrees out of phase between the left and right eyes. CONCLUSIONS: The neonate and abnormally reared monkeys continued to have asymmetrical responses even after their eyes were paralyzed. Therefore, eye movements cannot be the source of the asymmetrical amplitudes of the VEPs, and the visual cortex is at least one source responsible for asymmetries observed in neonates and adults reared under abnormal visual inputs.

Contour detection threshold: repeatability and learning with 'contour cards'.

Human observers are able to locate contours that are defined solely on the basis of long-range, orientation-domain correlations. The integrity of the mechanisms responsible for second-order contour detection is disrupted by amblyopia (Kovacs et al., 1996; Hess et al., 1997) and it is therefore of interest to develop methods for assessing pediatric patients undergoing treatment for amblyopia. In this study, we have determined the inter-observer and test-retest reliability of a card-based test of second-order contour integration. The magnitude of practice effects was also assessed in both adult and pediatric patient groups. Contour detection thresholds were measured for a closed contour, defined by Gabor patches, embedded in a randomly oriented Gabor-patch background. The visibility of the contour was controlled by varying the density of the background elements. Thresholds, defined in terms of the ratio of contour element spacing to average background spacing were measured with a clinical staircase procedure. Thresholds measured by two observers differed on average by 0.023 +/- 0.075 or about one half the increment between cards. Children and adults showed only small practice effects (0.022 +/- 0.051 vs 0.053 +/- 0.077, respectively) and average unsigned differences between repeated measures were equivalent to approximately 1 card across groups. A card-based test of second-order contour integration produces reliable estimates of contour integration performance in normal and amblyopic observers, including children.

Oscillatory motion but not pattern reversal elicits monocular motion VEP biases in infantile esotropia.

Patients with early disruptions of binocularity show cortical directional asymmetries in their steady state monocular VEP response to oscillatory motion. The VEP directional asymmetry is characterized by significant first harmonic components that show a 180 degrees difference in the response phase between the two eyes. By contrast, the normal response is dominated by even-order response harmonics, although some normal observers also have measurable responses at the first harmonic. Experiments and simulations were conducted to determine if the first harmonic in patients could reasonably be attributed to direction selective mechanisms. A secondary goal was to determine whether the first harmonic response of normals was also due to imbalances in direction selective mechanisms. Monocular steady state VEPs were elicited by oscillating 3 c/deg gratings presented at 6 and 10 Hz in normal observers and observers with infantile esotropia. Responses were also obtained to phase-reversing gratings of the same spatial and temporal frequencies. Phase reversal eliminated the majority of first harmonic responses which were recorded for normal observers to oscillatory motion. However, phase reversal did not elicit the cortical motion asymmetry in infantile esotropia. Modeling results suggest that the first harmonic response to oscillatory motion arises due to non-linearities in both direction selective and non-direction-selective mechanisms, with the latter being dominant in patients with early onset strabismus.

OKN, perceptual and VEP direction biases in strabismus.

The present study quantified nasalward/temporalward biases in monocular optokinetic nystagmus (MOKN) and perceived velocity in patients with either early onset esotropia, late onset esotropia and in normals. MOKN was measured with low spatial frequency, small-field gratings drifting at 9.4 degrees/s. MOKN bias was quantified as the ratio of nasalward slow-phase velocity divided by the sum of temporalward and nasalward slow-phase velocities (N/(N + T)). Observers also rated the perceived velocity of gratings moving in nasalward and temporalward directions (3 or 9.4 degrees/s) using a two interval forced choice task. MOKN and perceived velocity biases were correlated negatively in both early onset and late onset groups in the perceptual task--nasalward moving targets were rated as slower than temporalward targets, but in the MOKN task, slow-phase gain was higher for nasalward than for temporalward targets. Oscillatory-motion, visual evoked potentials (VEPs), were recorded in response to 1 c/deg gratings undergoing apparent motion at 10 Hz in a subset of the observers. VEP direction biases were quantified by calculating the ratio of first harmonic response amplitudes to the sum of first and second harmonic amplitudes. Significant correlations were found between the direction biases obtained on all three measures. Perceived velocity and MOKN bias measures were also correlated negatively. Patients with early onset esotropia (infantile esotropia) had larger biases than late onset esotropes or normals on each measure and the biases were more frequently bilateral in the early onset patients. The pattern of result is consistent with early critical periods for the mechanism(s) underlying MOKN, perceived velocity and cortical responsiveness. A single site model for all three asymmetries is unlikely, at least in simple form, because of the negative correlation between MOKN and perceived velocity biases and because of the differences in relative magnitude between the perceptual and MOKN biases.

Development of directional motion symmetry in the monocular visually evoked potential of infant monkeys.

Motion processing in humans and monkeys exhibit a directional asymmetry during infancy which is not present in adults except following abnormal visual rearing conditions. To characterize the time course for maturation of a symmetric response, we measured the monocular visually evoked potential (MVEP) response to 0.26 c/deg gratings oscillating horizontally at 6 Hz in 13 infant rhesus monkeys between 1 and 52 weeks of age. An asymmetric (F1) and a symmetric (F2) frequency component were extracted from the MVEP using Fourier analysis. At early ages the asymmetric F1 component measured from the two eyes exhibited a 180 deg interocular phase shift, demonstrating that there was a directional bias in opposite directions between the left and right eyes. Although our methods could not determine whether the bias was in the nasal or temporal direction, our results would be consistent with a nasal bias, as has been observed in previous motion studies. Magnitude of the asymmetry was quantified in the form of an asymmetry index, F1/(F1 + F2). Based on developmental changes in the asymmetry index, and phase and amplitudes of F1 and F2, we conclude that the MVEP loses its directional asymmetry at 6 weeks of age. The development of directional motion symmetry observed in monkeys over the first 6 weeks is similar to that observed in humans over the first 5 months.

Neural noise limitations on infant visual sensitivity.

Visual contrast sensitivity is poor in newborn human infants, but improves rapidly to approach adult levels by 8 months of age. During this period, infant sensitivity can be limited by physical factors affecting photon capture, such as eye size and photoreceptor density. Here we show that infant visual sensitivity is also limited by high levels of noise in the neural transduction process. Using a non-invasive electrophysiological measurement and a visual noise titration technique, we have found that intrinsic neural noise in neonates is approximately nine times higher than in adults. As intrinsic neural noise decreases during infancy, contrast sensitivity improves proportionally, suggesting that neural noise places critical limits on contrast sensitivity throughout development. Moreover, contrast gain control, an inhibitory process that adjusts visual responses to changing stimulation, is in place and operating in infants as young as 6 weeks of age, in spite of high levels of neural noise and significant immaturities in contrast sensitivity. The contrast gain control that we observed in human neonates may serve as a building block for more complex forms of visual inhibition, which develop later in infancy.