Vision after early-onset lesions of the occipital cortex: I. Neuropsychological and psychophysical studies.

We analyzed the visual functions of two patients (MS, FJ) with bilateral lesion of the primary visual cortex, which occurred at gestational age 33 wk in MS and at postnatal month 7 in FJ. In both patients basic visual functions--visual acuity, contrast sensitivity, color, form, motion perception-are similarly preserved or modestly impaired. Functions requiring higher visual processing, particularly figure-ground segregation based on textural cues, are severely impaired. In MS, studied longitudinally, the deficits attenuated between the ages of 4.5 and 8 y, suggesting that the developing visual system can display a considerable degree of adaptive plasticity several years after the occurrence of a lesion. In FJ (age 18:9 to 20:6 y), who is more impaired, the recovery, if any, was less.

Vision after early-onset lesions of the occipital cortex: II. Physiological studies.

In one of two patients (MS and FJ) with bilateral, early-onset lesion of the primary visual cortex, Kiper et al. (2002) observed a considerable degree of functional recovery. To clarify the physiological mechanisms involved in the recovery, we used fMRI and quantitative EEG to study both patients. The fMRI investigations indicated that in both patients, isolated islands of the primary visual cortex are functioning, in the right hemisphere in MS and in the left in FJ. The functional recovery observed in MS roughly correlated with the functional maturation of interhemispheric connections and might reflect the role of corticocortical connectivity in visual perception. The functionality of interhemispheric connections was assessed by analyzing the changes in occipital inter-hemispheric coherence of EEG signals (ICoh) evoked by moving gratings. In the patient MS, this ICoh response was present at 7:11 y and was more mature at 9:2 y. In the more visually impaired patient, FJ, a consistent increase in ICoh to visual stimuli could not be obtained, possibly because of the later occurrence of the lesion.

Visual stimulus-dependent changes in interhemispheric EEG coherence in ferrets.

In recent years, the analysis of the coherence between signals recorded from the scalp [electroencephalographic (EEG) coherence] has been used to assess the functional properties of cortico-cortical connections, both in animal models and in humans. However, the experimental validation of this technique is still scarce. Therefore we applied it to the study of the callosal connections between the visual areas of the two hemispheres, because this particular set of cortico-cortical connections can be activated in a selective way by visual stimuli. Indeed, in primary and in low-order secondary visual areas, callosal axons interconnect selectively regions, which represent a narrow portion of the visual field straddling the vertical meridian and, within these regions, neurons that prefer the same stimulus orientation. Thus only isooriented stimuli located near the vertical meridian are expected to change interhemispheric coherence by activating callosal connections. Finally, if such changes are found and are indeed mediated by callosal connections, they should disappear after transection of the corpus callosum. We perfomed experiments on seven paralyzed and anesthetized ferrets, recording their cortical activity with epidural electrodes on areas 17/18, 19, and lateral suprasylvian, during different forms of visual stimulation. As expected, we found that bilateral iso-oriented stimuli near the vertical meridian, or extending across it, caused a significant increase in interhemispheric coherence in the EEG beta-gamma band. Stimuli with different orientations, stimuli located far from the vertical meridian, as well as unilateral stimuli failed to affect interhemispheric EEG coherence. The stimulus-induced increase in coherence disappeared after surgical transection of the corpus callosum. The results suggest that the activation of cortico-cortical connections can indeed be revealed as a change in EEG coherence. The latter can therefore be validly used to investigate the functionality of cortico-cortical connections.

Visual stimulus-dependent changes in interhemispheric EEG coherence in humans.

We analyzed the coherence of electroencephalographic (EEG) signals recorded symmetrically from the two hemispheres, while subjects (n = 9) were viewing visual stimuli. Considering the many common features of the callosal connectivity in mammals, we expected that, as in our animal studies, interhemispheric coherence (ICoh) would increase only with bilateral iso-oriented gratings located close to the vertical meridian of the visual field, or extending across it. Indeed, a single grating that extended across the vertical meridian significantly increased the EEG ICoh in normal adult subjects. These ICoh responses were obtained from occipital and parietal derivations and were restricted to the gamma frequency band. They were detectable with different EEG references and were robust across and within subjects. Other unilateral and bilateral stimuli, including identical gratings that were effective in anesthetized animals, did not affect ICoh in humans. This fact suggests the existence of regulatory influences, possibly of a top-down kind, on the pattern of callosal activation in conscious human subjects. In addition to establishing the validity of EEG coherence analysis for assaying cortico-cortical connectivity, this study extends to the human brain the finding that visual stimuli cause interhemispheric synchronization, particularly in frequencies of the gamma band. It also indicates that the synchronization is carried out by cortico-cortical connection and suggests similarities in the organization of visual callosal connections in animals and in man.

On nature and limits of cortical developmental plasticity after an early lesion, in a child.

MS is a little girl who suffered severe, bilateral destruction of her primary visual areas at six weeks, after premature birth at 30 weeks. Between the ages of 4.5 and 5.5 years she partially recovered different aspects of visual function, and, in particular, the ability to segregate figures from background, based on texture cues. The recovery might have been due to the compensatory role of the remaining visual areas that could have acquired response properties similar to those of the primary visual areas. This is not supported by the available FMRI (functional magnetic resonance imaging) responses to visual stimuli. Instead, abnormalities in the pattern of stimulus-induced changes of interhemi-spheric EEG-coherence in this patient suggest that her visual callosal connections, and possibly other cortico-cortical connections have re-organized abnormally. Since cortico-cortical connections, including the callosal ones appear to be involved in perceptual binding and figure-background segregation, their reorganization could be an important element in the functional recovery after early lesion, and/or in the residual perceptual impairment.

Neuronal correlates of amblyopia in the visual cortex of macaque monkeys with experimental strabismus and anisometropia.

Amblyopia is a developmental disorder of pattern vision. After surgical creation of esotropic strabismus in the first weeks of life or after wearing -10 diopter contact lenses in one eye to simulate anisometropia during the first months of life, macaques often develop amblyopia. We studied the response properties of visual cortex neurons in six amblyopic macaques; three monkeys were anisometropic, and three were strabismic. In all monkeys, cortical binocularity was reduced. In anisometropes, the amblyopic eye influenced a relatively small proportion of cortical neurons; in strabismics, the influence of the two eyes was more nearly equal. The severity of amblyopia was related to the relative strength of the input of the amblyopic eye to the cortex only for the more seriously affected amblyopes. Measurements of the spatial frequency tuning and contrast sensitivity of cortical neurons showed few differences between the eyes for the three less severe amblyopes (two strabismic and one anisometropic). In the three more severely affected animals (one strabismic and two anisometropic), the optimal spatial frequency and spatial resolution of cortical neurons driven by the amblyopic eye were substantially and significantly lower than for neurons driven by the nonamblyopic eye. There were no reliable differences in neuronal contrast sensitivity between the eyes. A sample of neurons recorded from cortex representing the peripheral visual field showed no interocular differences, suggesting that the effects of amblyopia were more pronounced in portions of the cortex subserving foveal vision. Qualitatively, abnormalities in both the eye dominance and spatial properties of visual cortex neurons were related on a case-by-case basis to the depth of amblyopia. Quantitative analysis suggests, however, that these abnormalities alone do not explain the full range of visual deficits in amblyopia. Studies of extrastriate cortical areas may uncover further abnormalities that explain these deficits.

Functional organization of owl monkey lateral geniculate nucleus and visual cortex.

The nocturnal, New World owl monkey (Aotus trivirgatus) has a rod-dominated retina containing only a single cone type, supporting only the most rudimentary color vision. However, it does have well-developed magnocellular (M) and parvocellular (P) retinostriate pathways and striate cortical architecture [as defined by the pattern of staining for the activity-dependent marker cytochrome oxidase (CO)] similar to that seen in diurnal primates. We recorded from single neurons in anesthetized, paralyzed owl monkeys using drifting, luminance-modulated sinusoidal gratings, comparing receptive field properties of M and P neurons in the lateral geniculate nucleus and in V1 neurons assigned to CO "blob," "edge," and "interblob" regions and across layers. Tested with achromatic stimuli, the receptive field properties of M and P neurons resembled those reported for other primates. The contrast sensitivity of P cells in the owl monkey was similar to that of P cells in the macaque, but the contrast sensitivities of M cells in the owl monkey were markedly lower than those in the macaque. We found no differences in eye dominance, orientation, or spatial frequency tuning, temporal frequency tuning, or contrast response for V1 neurons assigned to different CO compartments; we did find fewer direction-selective cells in blobs than in other compartments. We noticed laminar differences in some receptive field properties. Cells in the supragranular layers preferred higher spatial and lower temporal frequencies and had lower contrast sensitivity than did cells in the granular and infragranular layers. Our data suggest that the receptive field properties across functional compartments in V1 are quite homogeneous, inconsistent with the notion that CO blobs anatomically segregate signals from different functional "streams."

Functional properties of neurons in macaque area V3.

We investigated the functional properties of neurons in extrastriate area V3. V3 receives inputs from both magno- and parvocellular pathways and has prominent projections to both the middle temporal area (area MT) and V4. It may therefore represent an important site for integration and transformation of visual signals. We recorded the activity of single units representing the central 10 degrees in anesthetized, paralyzed macaque monkeys. We measured each cell's spatial, temporal, chromatic, and motion properties with the use of a variety of stimuli. Results were compared with measurements made in V2 neurons at similar eccentricities. Similar to area V2, most of the neurons in our sample (80%) were orientation selective, and the distribution of orientation bandwidths was similar to that found in V2. Neurons in V3 preferred lower spatial and higher temporal frequencies than V2 neurons. Contrast thresholds of V3 neurons were extremely low. Achromatic contrast sensitivity was much higher than in V2, and similar to that found in MT. About 40% of all neurons showed strong directional selectivity. We did not find strongly directional cells in layer 4 of V3, the layer in which the bulk of V1 and V2 inputs terminate. This property seems to be developed within area V3. An analysis of the responses of directionally selective cells to plaid patterns showed that in area V3, as in MT and unlike in V1 and V2, there exist cells sensitive to the motion of the plaid pattern rather than to that of the components. The exact proportion of cells classified as being selective to color depended to a large degree on the experiment and on the criteria used for classification. With the use of the same conditions as in a previous study of V2 cells, we found as many (54%) color-selective cells as in V2 (50%). Furthermore, the responses of V3 cells to colored sinusoidal gratings were well described by a linear combination of cone inputs. The two subpopulations of cells responsive to color and to motion overlapped to a large extent, and we found a significant proportion of cells that gave reliable and directional responses to drifting isoluminant gratings. Our results show that there is a significant interaction between color and motion processing in area V3, and that V3 cells exhibit the more complex motion properties typically observed at later stages of visual processing.

Chromatic properties of neurons in macaque area V2.

We recorded from single cells in area V2 of cynomolgus monkeys using standard acute recording techniques. After measuring each cell's spatial and temporal properties, we performed several tests of its chromatic properties using sine-wave gratings modulated around a mean gray background. Most cells behaved like neurons in area V1 and their responses were adequately described by a model that assumes a linear combination of cone signals. Unlike in V1, we found a subpopulation of cells whose activity was increased or inhibited by stimuli within a narrow range of color combinations. No particular color directions were preferentially represented. V2 cells showing color specificity, including cells showing narrow chromatic tuning, were present in any of the stripe compartments, as defined by cytochrome-oxidase (CO) staining. An addition of chromatic contrast facilitated the responses of most neurons to gratings with various luminance contrasts. Neurons in all three CO compartments gave significant responses to isoluminant gratings. Receptive-field properties of cells were generally similar for luminance and chromatically defined stimuli. We found only a small number of cells with a clearly identifiable double-opponent receptive-field organization.

Growth of callosal terminal arbors in primary visual areas of the cat.

In kittens ranging in age between postnatal day (P) 5 and P150, callosal axons originating near the 17/18 border were anterogradely labelled with biocytin and reconstructed from serial sections. At the end of the first postnatal week most of the axons begin to invade the cortex near the 17/18 border with multiple branches; some axons already span the grey matter up to layer 1. Branches tend to grow into the grey matter in loose bundles

Cortical oscillatory responses do not affect visual segmentation.

We tested the hypothesis that synchronization of oscillatory responses between populations of visually driven neurons could be the basis for visual segmentation and perceptual grouping. We reasoned that oscillations in response induced by flickering visual targets should have an effect on visual performance in these tasks. We therefore measured the psychophysical performance of human subjects in a texture segregation task. (Expt I) and in a perceptual grouping task (Expt II). In both experiments, the elements composing the stimuli were flickered and presented in a variety of flicker conditions. These experimental conditions were designed to either interfere with naturally occurring synchronization of oscillations, or to induce synchronization and bias a subject's perceptual judgment. Performance in these tasks was neither helped nor hindered by the temporal pattern of flicker. These results suggest that physiologically observed oscillatory responses are unrelated to the processes underlying visual segmentation and perceptual grouping.

Development of contrast sensitivity across the visual field in macaque monkeys (Macaca nemestrina).

Interpretation of measurements of visual performance in infants must be based on knowledge of the locus of highest sensitivity in the infant retina. While we know that adult contrast sensitivity and spatial resolution is highest at the fovea, recent anatomical data show that the infant fovea is relatively immature. We have studied that variation of contrast sensitivity across the visual field during development in infant monkeys in order to investigate the behavioral consequences of this immaturity. The results show that, unlike adults, the sensitivity of the infant foveal region is similar to that of the near periphery. Central contrast sensitivity and spatial resolution improve substantially relative to the periphery over the first 20-40 postnatal weeks. Thus, contrast sensitivity in the periphery is relatively mature in infants with respect to more central regions of the visual field. The maturation pattern seen behaviorally is consistent with physiological and anatomical maturation patterns in macaque monkey.

Processing of color, form, and motion in macaque area V2.

We investigated the representation of color in cortical area V2 of macaque monkeys, and the association of color with other stimulus attributes. We measured the selectivity of individual V2 neurons for color, motion, and form. Most neurons in V2 were orientation selective, about half of them were selective for color, and a minority of cells (about 20%) were selective for size or direction. We correlated these physiological measurements with the anatomical location of the cells with respect to the cytochrome oxidase (CO) compartments of area V2. There was a tendency for color-selective cells to be found more frequently in the thin stripes, but color-selective cells also occurred frequently in thick stripes and inter-stripes. We found no difference in the degree of color selectivity between the different CO compartments. Furthermore, there was no negative correlation between color selectivity and selectivity for other stimulus attributes. We found many cells capable of encoding information along more than one stimulus dimension, regardless of their location with respect to the CO compartments. We suggest that area V2 plays an important role in integrating information about color, motion, and form. By this integration of stimulus attributes a cue invariant representation of the visual world might be achieved.

Spatial frequency channels in experimentally strabismic monkeys revealed by oblique masking.

Although the spatial vision deficits of human strabismic amblyopes have been well documented, surprisingly little is known about the mechanisms underlying their visual performance. In an effort to reveal the structure underlying the spatial vision deficits associated with strabismic amblyopia, we measured the performance of monkeys (Macaca nemestrina) with experimental strabismus in a contrast detection task with oblique masks. The masks were two adjacent identical oblique sine-wave gratings modulated in space by a Gaussian envelope. The target stimulus was a vertically oriented Gabor patch that appeared superimposed on the center of either the left or the right mask. The animals were trained by operant methods to indicate the location of the target. We measured detection thresholds in each eye independently for a large number of test and mask spatial frequencies. For each test spatial frequency, detection thresholds were elevated in the presence of the mask. The threshold evaluations showed a peak for a particular spatial frequency that was typically similar to the test spatial frequency. This pattern of results is consistent with the idea that the tests are detected by a discrete number of channels tuned to a narrow range of spatial frequencies. The data from the deviated eyes did not appear qualitatively different from those of the fellow eyes, and could be accounted by the same number of channels in both eyes. Quantitative estimates of the channels' characteristics revealed that the channels derived from the deviated eyes' data were similar to those yielded by the fellow eyes, but showed a reduction in their sensitivity to contrast.

Suprathreshold contrast sensitivity in experimentally strabismic monkeys.

Human strabismic amblyopes show deficits in spatial vision that can be revealed in a variety of visual tasks. In particular, they show a reduced sensitivity to contrast for a wide range of spatial frequencies. The ability of strabismic amblyopes to process contrast information at levels well above detection threshold is less well understood and somewhat controversial. In the course of investigating the neural basis of strabismic amblyopia we studied contrast processing both at and above detection threshold in experimentally strabismic monkeys (Macaca nemestrina). First we trained them to perform a contrast detection task and measured their contrast sensitivity for a wide range of spatial frequencies. Then we trained them to discriminate between two gratings that were identical except for their contrast. We show that these monkeys exhibit deficits in both tasks. The deficits in the contrast discrimination task cannot be solely attributed to their deficit at threshold.

Receptive fields and functional architecture of macaque V2.

1. Visual area V2 of macaque monkey cerebral cortex is the largest of the extrastriate visual areas, yet surprisingly little is known of its neuronal properties. We have made a quantitative analysis of V2 receptive field properties. Our set of measurements was chosen to distinguish neuronal responses reflecting parvocellular (P) or magnocellular (M) inputs and to permit comparison with similar measurements made in other visual areas; we further describe the relationship of those properties to the laminar and cytochrome oxidase (CO) architecture of V2. 2. We recorded the activity of single units representing the central 5 degrees in all laminae and CO divisions of V2 in anesthetized, paralyzed macaque monkeys. We studied responses to geometric targets and to drifting sinusoidal gratings that varied in orientation, spatial frequency, drift rate, contrast, and color. 3. The orientation selectivity and spatial and temporal tuning of V2 neurons differed little from those in V1. As in V1, spatial and temporal tuning in V2 appeared separable, and we identified a population of simple cells (more common within the central 3 degrees) similar to those found in V1. Contrast sensitivity of V2 neurons was greater on average than in V1, perhaps reflecting the summation of inputs in V2's larger receptive fields. Many V2 neurons exhibited some degree of chromatic opponency, responding to isoluminant color variations, but these neurons differed from V1 in the linearity with which they summate cone signals. 4. In agreement with others, we found that neurons with selective responses to color, size, and motion did seem to cluster in different CO compartments. However, this segregation of qualitatively different response selectivities was not absolute, and response properties also seemed to depend on laminar position within each compartment. As others also have noted, we found that CO stripe widths in the macaque (unlike in the squirrel monkey) did not consistently appear different. We relied on the segregation of qualitatively distinct cell types, and in some cases the pattern of Cat-301 staining as well, to distinguish CO stripes when the staining pattern of CO alone was ambiguous. Although all cell types were found in all CO compartments and laminae, unoriented cells were more prominent in layers 2-4 of "thin" stripes, direction-selective cells in layers 3B/4 of "thick" stripes, color-selective cells in the upper layers of thin and pale stripes, and end-stopped cells mainly outside of layer 4 in thin stripes.(ABSTRACT TRUNCATED AT 400 WORDS)

Chromatic properties of neurons in macaque MT.

We have studied the responses of MT neurons to moving gratings, spatially modulated in luminance and chromaticity. Most MT neurons responded briskly and with high contrast sensitivity to targets whose luminance was modulated, with or without added chromatic contrast. When luminance modulation was removed and only chromatic stimulation was used, the responses of all MT neurons were attenuated. Most were completely unresponsive to stimulation with targets whose modulation fell within a "null" plane in color space; these null planes varied from neuron to neuron, but all lay close to the plane of constant photometric luminance. For about a third of the neurons, there was no color direction in which responses were completely abolished; almost all of these neurons had a definite minimum response for chromatic modulation near the isoluminant plane. MT neurons that responded to isoluminant targets did so inconsistently and with poor contrast sensitivity, so that only intensely modulated targets were effective. Whereas the best thresholds of MT neurons for luminance targets are close to behavioral contrast threshold, the thresholds for isoluminant targets lie considerably above behavioral contrast threshold. Therefore, although some MT neurons do give responses to isoluminant targets, they are unlikely to be the source of the chromatic motion signals revealed behaviorally.

Spatial phase discrimination in monkeys with experimental strabismus.

Human strabismus amblyopes show deficits in spatial vision that are revealed in a variety of visual tasks. In particular, they show severe deficits in their ability to encode the relative spatial phase of the sinusoidal components in a compound grating. To investigate the neural basis of strabismic amblyopia we tested the ability of monkeys with experimentally induced strabismus to encode spatial phase relationships. First, we trained them to discriminate between compound gratings (made of a fundamental sinusoid and its third harmonic) that differed only in the relative phase of their components. These monkeys exhibited a pattern of severe deficits that resemble those described in the human population of strabismic amblyopes. We conclude that these animals represent a valid model of strabismic amblyopia. Second, we show that a model that had been used to account for the performance of normal human subjects and of humans with anisometropic amblyopia fails to predict the performance of monkeys with strabismic amblyopia.

Contrast sensitivity and vernier acuity in amblyopic monkeys.

Human psychophysical studies suggest that strabismic and anisometropic amblyopes may have characteristically different patterns of visual loss. In particular, anisometropic amblyopes often show deficits on spatial localization tasks that scale with their spatial resolution losses, whereas strabismic amblyopes can show localization deficits that are large relative to their losses in spatial resolution. We have compared the performance of non-human primates with experimentally-induced anisometropic and strabismic amblyopia on contrast detection and vernier acuity tasks. The performance of both groups of animals was fundamentally similar: both strabismic and anisometropic monkeys showed deficits in spatial localization that were large relative to their resolution losses, although the animals with the most disproportionate losses were strabismic. We investigated the extent to which contrast sensitivity losses accounted for the vernier acuity deficits. The results showed that, in most cases of either strabismic or anisometropic amblyopia, when the vernier stimuli for each eye were equated in terms of effective contrast, the extent of the vernier acuity deficit was reduced to approximately the extent of the spatial resolution deficit. In two cases, both of strabismic amblyopia, we found that equating the stimuli in this way was not sufficient to make the deficits equal, a pattern that has been described for human strabismic amblyopes.

Contrast detection in luminance and chromatic noise.

We measured detection thresholds for a vertically oriented 1.2-cycle-per-degree sine-wave grating embedded in spatiotemporal broadband noise. Noise and signal were modulated in different directions in color space around an equal-energy white point. When signal and noise were modulated in the same direction, we observed a linear relationship between noise spectral density and signal energy at threshold. The slope of this function was the same whether the modulation was along a luminance axis or a red-green axis. If the signal was on one axis and the noise was on the other, no masking was observed. These results support the notion of two independent and equally efficient mechanisms tuned to these directions. We then measured threshold elevations for masks with both chromatic and luminance components. When signal and noise were modulated along the same line (for example, bright red and dark green), thresholds were elevated. When we inverted the phase of the chromatic component of the noise relative to the luminance component (bright green and dark red), the masking effect disappeared, even though the amount of noise in the putative luminance and chromatic mechanisms was exactly the same as before. This implies that detection performance is limited by mechanisms sensitive to both luminance and chromatic contrast signals. We characterized these mechanisms by their spectral tuning curves.