Abnormal Early Visual Experience Research Articles

Orientation Tuning and Contrast Dependence of Continuous Flash Suppression in Amblyopia and Normal Vision.

Suppression in amblyopia may be an unequal form of normal interocular suppression or a distinct pathophysiology. To explore this issue, we examined the orientation tuning and contrast dependence of continuous flash suppression (CFS) in adults with amblyopia and visually normal controls. Nine patients (mean age, 26.9 ± SD 4.7 years) and 11 controls (mean age, 24.8 ± SD 5.3 years) participated. In the CFS paradigm, spatially one-dimensional noise refreshing at 10 Hz was displayed in one eye to induce suppression of the other eye, and suppression strength was measured by using a grating contrast increment detection task. In experiment 1, noise contrast was fixed and the orientation difference between the noise and the grating was varied. In experiment 2, noise and grating orientations were identical and noise contrast was varied. Suppression patterns varied in both groups. In experiment 1, controls showed consistently orientation-tuned CFS (mean half-height bandwidth, 35.8° ± SD 21.5°) with near-equal strength between eyes. Five of nine patients with amblyopia exhibited orientation-independent CFS. Eight patients had markedly unequal suppression between eyes. Experiment 2 found that increasing the noise contrast to the amblyopic eye may produce suppression of the fellow eye, but suppression remained unequal between eyes. Our data revealed that orientation specificity in CFS was very broad or absent in some patients with amblyopia, which could not be predicted by clinical measures. Suppression was unbalanced across the entire contrast range for most patients. This suggests that abnormal early visual experience disrupts the development of interocular suppression mechanisms.

Asymmetric Dichoptic Masking in Visual Cortex of Amblyopic Macaque Monkeys.

In amblyopia, abnormal visual experience leads to an extreme form of eye dominance, in which vision through the nondominant eye is degraded. A key aspect of this disorder is perceptual suppression: the image seen by the stronger eye often dominates during binocular viewing, blocking the image of the weaker eye from reaching awareness. Interocular suppression is the focus of ongoing work aimed at understanding and treating amblyopia, yet its physiological basis remains unknown. We measured binocular interactions in visual cortex of anesthetized amblyopic monkeys (female Macaca nemestrina), using 96-channel "Utah" arrays to record from populations of neurons in V1 and V2. In an experiment reported recently (Hallum et al., 2017), we found that reduced excitatory input from the amblyopic eye (AE) revealed a form of balanced binocular suppression that is unaltered in amblyopia. Here, we report on the modulation of the gain of excitatory signals from the AE by signals from its dominant fellow eye (FE). Using a dichoptic masking technique, we found that AE responses to grating stimuli were attenuated by the presentation of a noise mask to the FE, as in a normal control animal. Responses to FE stimuli, by contrast, could not be masked from the AE. We conclude that a weakened ability of the amblyopic eye to modulate cortical response gain creates an imbalance of suppression that favors the dominant eye.SIGNIFICANCE STATEMENT In amblyopia, vision in one eye is impaired as a result of abnormal early visual experience. Behavioral observations in humans with amblyopia suggest that much of their visual loss is due to active suppression of their amblyopic eye. Here we describe experiments in which we studied binocular interactions in macaques with experimentally induced amblyopia. In normal monkeys, the gain of neuronal response to stimulation of one eye is modulated by contrast in the other eye, but in monkeys with amblyopia the balance of gain modulation is altered so that the weaker, amblyopic eye has little effect while the stronger fellow eye has a strong effect. This asymmetric suppression may be a key component of the perceptual losses in amblyopia.

Binocular visual training to promote recovery from monocular deprivation.

Abnormal early visual experience often leads to poor vision, a condition called amblyopia. Two recent approaches to treating amblyopia include binocular therapies and intensive visual training. These reflect the emerging view that amblyopia is a binocular deficit caused by increased neural noise and poor signal-in-noise integration. Most perceptual learning studies have used monocular training; however, a recent study has shown that binocular training is effective for improving acuity in adult human amblyopes. We used an animal model of amblyopia, based on monocular deprivation, to compare the effect of binocular training either during or after the critical period for ocular dominance plasticity (early binocular training vs. late binocular training). We used a high-contrast, orientation-in-noise stimulus to drive the visual cortex because neurophysiological findings suggest that binocular training may allow the nondeprived eye to teach the deprived eye's circuits to function. We found that both early and late binocular training promoted good visual recovery. Surprisingly, we found that monocular deprivation caused a permanent deficit in the vision of both eyes, which became evident only as a sleeper effect following many weeks of visual training.

Sensitivity to synchronicity of biological motion in normal and amblyopic vision

Amblyopia is a developmental disorder of spatial vision that results from abnormal early visual experience usually due to the presence of strabismus, anisometropia, or both strabismus and anisometropia. Amblyopia results in a range of visual deficits that cannot be corrected by optics because the deficits reflect neural abnormalities. Biological motion refers to the motion patterns of living organisms, and is normally displayed as points of lights positioned at the major joints of the body. In this experiment, our goal was twofold. We wished to examine whether the human visual system in people with amblyopia retained the higher-level processing capabilities to extract visual information from the synchronized actions of others, therefore retaining the ability to detect biological motion. Specifically, we wanted to determine if the synchronized interaction of two agents performing a dancing routine allowed the amblyopic observer to use the actions of one agent to predict the expected actions of a second agent. We also wished to establish whether synchronicity sensitivity (detection of synchronized versus desynchronized interactions) is impaired in amblyopic observers relative to normal observers. The two aims are differentiated in that the first aim looks at whether synchronized actions result in improved expected action predictions while the second aim quantitatively compares synchronicity sensitivity, or the ratio of desynchronized to synchronized detection sensitivities, to determine if there is a difference between normal and amblyopic observers. Our results show that the ability to detect biological motion requires more samples in both eyes of amblyopes than in normal control observers. The increased sample threshold is not the result of low-level losses but may reflect losses in feature integration due to undersampling in the amblyopic visual system. However, like normal observers, amblyopes are more sensitive to synchronized versus desynchronized interactions, indicating that higher-level processing of biological motion remains intact. We also found no impairment in synchronicity sensitivity in the amblyopic visual system relative to the normal visual system. Since there is no impairment in synchronicity sensitivity in either the non-amblyopic or amblyopic eye of amblyopes, our results suggest that the higher order processing of biological motion is intact.

Scale-dependent loss of global form perception in strabismic amblyopia

Amblyopic humans are known to have a range of spatial vision abnormalities. Prior studies have documented amblyopic deficits in global form perception but have typically used only one set of stimulus parameters. Our aim in this study was to examine the extent and nature of global form perception deficits in strabismic amblyopia using a range of spatial scales and pattern types. Glass patterns are random dot stimuli in which the local orientations of paired dots must be integrated over space to yield a global form percept. We measured coherence thresholds for discrimination of pattern structure in translational (linear) and concentric Glass patterns at three spatial scales in two control and six amblyopic observers. We found that sensitivity to Glass patterns depended on both spatial scale and pattern type in all observers. Participants with a history of abnormal early visual experience showed greater interocular threshold difference when the discrimination was based on translational patterns than when it was based on concentric patterns, and the degree of amblyopic loss was greatest at fine spatial scale. Our results show that the nature and extent of global form vision deficits vary substantially with stimulus parameters and are greatest at fine spatial scales.

Retinotopic maps and foveal suppression in the visual cortex of amblyopic adults

Amblyopia is a developmental visual disorder associated with loss of monocular acuity and sensitivity as well as profound alterations in binocular integration. Abnormal connections in visual cortex are known to underlie this loss, but the extent to which these abnormalities are regionally or retinotopically specific has not been fully determined. This functional magnetic resonance imaging (fMRI) study compared the retinotopic maps in visual cortex produced by each individual eye in 19 adults (7 esotropic strabismics, 6 anisometropes and 6 controls). In our standard viewing condition, the non-tested eye viewed a dichoptic homogeneous mid-level grey stimulus, thereby permitting some degree of binocular interaction. Regions-of-interest analysis was performed for extrafoveal V1, extrafoveal V2 and the foveal representation at the occipital pole. In general, the blood oxygenation level-dependent (BOLD) signal was reduced for the amblyopic eye. At the occipital pole, population receptive fields were shifted to represent more parafoveal locations for the amblyopic eye, compared with the fellow eye, in some subjects. Interestingly, occluding the fellow eye caused an expanded foveal representation for the amblyopic eye in one early-onset strabismic subject with binocular suppression, indicating real-time cortical remapping. In addition, a few subjects actually showed increased activity in parietal and temporal cortex when viewing with the amblyopic eye. We conclude that, even in a heterogeneous population, abnormal early visual experience commonly leads to regionally specific cortical adaptations.

Effects of alternating monocular occlusion on the development of visual callosal connections

During normal postnatal development there is a partial elimination of the callosal projections of cortical areas 17 and 18 in the cat. Visual experience early in life can modulate this process. In the present study, we investigated how restricting visual experience to alternating monocular occlusion affects the development of the callosal connections of cortical areas 17 and 18. Alternating monocular occlusion exaggerates the normally occurring partial elimination of immature callosal projection: it causes a significant reduction in the total number of neurons in the supragranular layers that send an axon through the corpus callosum and marginally increases the distribution of these neurons across areas 17 and 18. Examination of these data in the context of the effects of other types of abnormal early visual experience on the corpus callosum and on the anatomy and physiology of areas 17 and 18 indicates that the postnatal development of the corpus callosum is under the control of multiple, interacting influences which differ in the magnitude and quality of their effects. The data also support the conclusion, drawn from our results in prior studies, that normal visual stimulation is necessary for the stabilization of the normal complement of callosal projections.

Human amblyopia: structure of the visual field

Kittens raised with different kinds of abnormal early visual experience (monocular and binocular deprivation, convergent strabismus, eye rotation, asymmetric alternating occlusion, early callosal split) show systematic deficits in the nasal visual field of the affected eye. To test whether abnormal visual experience produces similar deficits in the human visual system, we measured the monocular visual field of humans with subnormal binocular vision (strabismic and anisometropic amblyopes, strabismics with alternating fixation). Eight amblyopes were tested with a computer-assisted static perimetry (Octopus 2000). Twenty other subjects were tested with kinetic perimetry (Goldmann 940), 11 subjects with static perimetry (Goldmann 940). In some of these subjects, we measured the latency of saccades and the accuracy of visually guided pointing toward stimuli presented in the peripheral visual field. Both strabismic and anisometropic amblyopes frequently showed deficits of visual sensitivity in the central part of the visual field, but no systematic deficits in the peripheral field of the amblyopic eyes. Strabismic alternators had practically equal fields in the two eyes. Neither saccadic latency nor pointing accuracy showed a systematic impairment in the nasal visual field. The discrepancy between the field losses in strabismic humans and in cats raised with a surgically induced squint cannot be due to methodological differences, but rather to anatomical differences, or to the different origin of strabismus in the two species.

Differential development of two visual functions in primates.

Psychophysical data suggest that spatial resolution and spatial position sensitivity may be limited by different neural mechanisms. We investigated this hypothesis from a developmental perspective by studying the development of these two kinds of visual performance in two groups of infant macaque monkeys (Macaca nemestrina), one normal and one given an experimental strabismus. The results show that these two visual functions develop at different rates in normal monkeys and are disrupted differentially by abnormal early visual experience. However the relationship between the two measures is the same in strabismic and normally reared monkeys; the performance of strabismic monkeys resembles that of younger normal monkeys.

Behavioral studies on the effect of abnormal early visual experience in monkeys: Temporal modulation sensitivity

Temporal modulation sensitivity functions were investigated by behavioral methods in two monkeys reared with normal visual experience and 12 monkeys reared with abnormal early visual experience. Experimental treatments were initiated when the animals were approximately one month of age. Two monkeys were each treated with one of the following procedures: (1) long-term monocular lid suture. (2) short-term monocular lid suture. (3) surgically induced esotropia. (4) surgically induced exotropia. (5) optical dissociation of binocular vision with ophthalmic prisms (6) chronic monocular cycloplegia. The temporal modulation sensitivity functions for uniform field flicker for both eyes of the control subjects and for the untreated eyes of the experimental subjects were similar to functions for humans measured on the same apparatus using the same behavioral procedures. All eight of the monkeys preconditioned by lid suture or surgically induced strabismus showed reduced sensitivity at all temporal frequencies with the difference between the experimental and control eyes being larger for the high than low temporal frequencies. The monkeys reared with optical dissociation of binocular vision or chronic monocular cycloplegia showed equal temporal modulation sensitivities of the two eyes, but failed to show binocular summation. It was concluded from these studies that abnormal early visual experience in monkeys results in deficiencies in the processing of both spatial and temporal information, but the differences between the treated and untreated eyes were usually greater in the spatial domain than the temporal domain.

Behavioral studies on the effect of abnormal early visual experience in monkeys: Spatial modulation sensitivity

Spatial modulation sensitivity functions have been investigated by behavioral methods in two monkeys reared with normal visual experience and 12 monkeys reared with abnormal, early visual experience. Experimental treatments were initiated when the animals were approximately one month of age. Two monkeys were each treated with one of the following procedures: (1) long-term monocular lid suture. (2) short-term monocular lid suture. (3) surgically induced esotropia. (4) surgically induced exotropia. (5) optical dissociation of binocular vision with ophthalmic prisms (6) chronic monocular cycloplegia. The results of the studies showed a severe loss of contrast sensitivity of the treated eyes compared to the control eyes for monkeys reared with monocular lid suture or surgically induced esotropia. Surgically induced exotropia resulted in a moderate reduction in sensitivity of the deviated eye while optical dissociation resulted in a mild reduction in sensitivity of one eye compared to the other. One of the two monkeys reared for seven months with chronic monocular cyclopegia had a relative reduction in contrast sensitivity of the treated eye, but the other monkey had equal sensitivities in the two eyes. However, binocular summation experiments showed that even though the relative difference between the monocular sensitivities was small or absent for the monkeys reared with optical dissociation or chronic monocular cycloplegia, none of them demonstrated binocular vision in these experiments.

Electrophysiological Evidence that Abnormal Early Visual Experience Can Modify the Human Brain

In the caption of the cover photograph for 25 May 1973, the word "below" is misplaced; it should be deleted from the first sentence, and the second sentence should read: "(Below) Same view taken through a cylindrical lens . . ." Two errors occurred in the report by Freeman and Thibos in the same issue, p. 876: in column 2, line 4, "Freeman and co-workers" should be changed to "Freeman et al." in column 3, line 44, "the visual resolution" should be changed to "visual resolution"-Ed.

Electrophysiological evidence that abnormal early visual experience can modify the human brain.

Visual resolution in humans is nearly equal for vertically and horizontally oriented detail, but for some subjects there is a substantial difference in resolving power for these orientations. Although subjects who exhibit this difference invariably have ocular astigmatism, optical explanations of the effect can be ruled out. Direct evidence has been found for an electrophysiological correlate to the psychophysical finding. Subjects who have reduced resolution for a pattern of a particular orientation also show a decreased evoked potential response elicited by a target of the same orientation. The results are consistent with the hypothesis that a deficiency of specific features in the early visual input can alter the organization of the visual pathways.

Meridional amblyopia: Evidence for modification of the human visual system by early visual experience

Subjects with ocular astigmatism habitually experience contours of one orientation as clearer than all others. The largest difference in clarity is between lines oriented parallel to to the two principal meridians, which in the vast majority of cases lie close to vertical and horizontal. In contrast to normal subjects, many astigmats after full correction of their refractive error show large differences in their acuity for gratings of these two orientations. The acuity is substantially reduced for the orientation which is habitually the most defocused by the astigmatic optics. We have shown (a) that the reduced acuity is of neural origin, (b) that it does not fully recover subsequent to optical correction of the astigmatism, and (c) that the amount by which acuity is reduced is correlated with the degree of astigmatism. It is argued that the abnormal early visual experience of an astigmat induces matching neural alterations to occur within the visual system, which in turn result in the substantial differences in the ability to resolve contours of different orientations.