Positional uncertainty in peripheral and amblyopic vision

Three experiments were performed to examine positional acuity and the role of spatial sampling in central, peripheral and amblyopic vision. In the first experiment, 3-line bisection acuity was compared to grating acuity. In normal foveal vision bisection acuity represents a hyperacuity. In anisometropic amblyopes, bisection acuity is reduced in rough proportion to their grating acuity. In strabismic amblyopes, and in the normal periphery, bisection acuity is reduced to a greater extent than grating acuity. This result implies that reduced contrast sensitivity of the spatial filters is not sufficient to account for the increased positional uncertainty found in peripheral vision and in strabismic amblyopia. In order to test the hypothesis that the high degree of positional uncertainty evident in these visual systems is a consequence of sparse spatial sampling, bisection thresholds and width discrimination thresholds were measured with stimuli comprised of discrete samples. The results showed that normal foveal vision and the vision of anisometropic amblyopes show little benefit from adding discrete samples to the stimulus. In contrast, the normal periphery, and the central field of strabismic amblyopes demonstrate marked positional uncertainty which can be efficiently reduced in proportion to the square root of the number of samples (up to about 10) comprising the stimulus in the direction orthogonal to the discrimination cue. In aggregate the results suggest that anisometropic and strabismic amblyopia are fundamentally different. The positional uncertainty in anisometropic amblyopia is consistent with the reduced sensitivity of the spatial filters. The data of the normal periphery and of the central field of strabismic amblyopes suggest that the cortical sampling grain imposes a fundamental limit upon their positional acuity.     

Sensitivity to visual motion in amblyopic macaque monkeys

Amblyopia is usually considered to be a deficit in spatial vision. But there is evidence that amblyopes may also suffer specific deficits in motion sensitivity as opposed to losses that can be explained by the known deficits in spatial vision. We measured sensitivity to visual motion in random dot displays for strabismic and anisometropic amblyopic monkeys. We used a wide range of spatial and temporal offsets and compared the performance of the fellow and amblyopic eye for each monkey. The amblyopes were severely impaired at detecting motion at fine spatial and long temporal offsets, corresponding to fine spatial scale and slow speeds. This impairment was also evident for the untreated fellow eyes of strabismic but not anisometropic amblyopes. Motion sensitivity functions for amblyopic eyes were shifted toward large spatial scales for amblyopic compared to fellow eyes, to a degree that was correlated with the shift in scale of the spatial contrast sensitivity function. Amblyopic losses in motion sensitivity, however, were not correlated with losses in spatial contrast sensitivity. This, combined with the specific impairment for detecting long temporal offsets, reveals a deficit in spatiotemporal integration in amblyopia which cannot be explained by the lower spatial resolution of amblyopic vision.     

The Glenn A. Fry award lecture: the "spatial grain" of the amblyopic visual system

This paper reviews psychophysical evidence that the visual performance and, by inference, the underlying neural losses of strabismic and anisometropic amblyopes are fundamentally different. The data of amblyopes are considered in the light of recent models for normal spatial vision. It is argued that the spatial deficits which are found in anisometropic amblyopes can be understood largely in terms of reduced resolution and contrast sensitivity, as would be expected on the basis of early experience with a defocused image in one eye. In contrast, the spatial deficits found in strabismic amblyopes are more profound than can be predicted on the basis of either resolution, or contrast sensitivity, and may have their basis in a coarse cortical spatial sampling grain.     

Spatial localization in normal and amblyopic vision

Spatial localization was investigated for each eye of amblyopic observers using a bisection paradigm. The stimuli were comprised of a grating composed of bright lines, and a test line. The test line was either placed above the grating (bisection-no overlap) or within the row of lines comprising the grating (bisection-with overlap) and thresholds for each bisection task were measured as a function of the fundamental spatial frequency of the grating. Vernier thresholds were also measured. For the nonamblyopic eyes at low spatial frequencies, bisection thresholds were a constant fraction ("Weber" fraction) of the space to be bisected, while at high spatial frequencies thresholds were approximately a constant retinal distance (a hyperacuity). However the spatial localization of an amblyopic eye depends upon both the type of amblyopia, and the stimulus configuration. Specifically, for anisometropic amblyopia, spatial localization (bisection-no overlap) and vernier, when scaled to the resolution losses, were normal. However, spatial adjacency (bisection with overlap), while enhancing the spatial localization of nonamblyopic eyes at high spatial frequencies, markedly elevated thresholds in the amblyopic eyes of anisometropic amblyopes. Strabismic amblyopes on the other hand show disturbances in both spatial localization tasks which can not be accounted for on the basis of reduced resolution. Their results are characterized by an absence of a constant Weber fraction at low spatial frequencies and "crowding" effects at high spatial frequencies. For strabismic amblyopes, the optimal localization thresholds were similar to the Snellen threshold, while for anisometropic amblyopes, the optimal localization thresholds were several times better than the Snellen threshold.     

Lateral interactions in amblyopia

We studied lateral neural interactions in strabismic (n=6) and anisometropic amblyopes (n=3) by measuring reductions in the perceived contrast of a foveally viewed Gabor centred in a horizontal array of closely neighboring Gabors. Strabismic amblyopes, but not anisometropic amblyopes, failed to show the reduction in perceived contrast typical of normal vision [J. Opt. Soc. Amer. A 15 (1998) 1733] when lateral contrast information is available at the same orientation and spatial frequency. The strabismic amblyopes also severely misperceive the regularity of the array of Gabors flanking the test stimulus. A normal eye could model the anomalous contrast perception of the amblyopic eye, by adding an equivalent amount of spatial distortion to the stimulus. The relationship between the observed anomalies for local contrast gain control and positional sensitivity is discussed.     

Binocular contrast summation and inhibition in amblyopia

The monocular contrast sensitivity loss in amblyopia is well documented. We investigated the influence of interocular sensitivity difference on binocular contrast sensitivity in amblyopia. Monocular and binocular contrast sensitivity functions of six amblyopes (three strabismic and three anisometropic) were measured. The monocular contrast sensitivity loss depended on the type of amblyope. Anisometropic amblyopes generally showed high frequency losses. Strabismic amblyopes showed losses at both low and high spatial frequencies. Binocular performance was assessed in terms of binocular ratios (binocular/non-amblyopic). A binocular ratio greater than 1 indicates binocular summation (binocular > monocular) while a ratio less than 1 shows binocular inhibition (binocular < monocular). In all subjects, the binocular ratio depended on the difference between the amblyopic and the non-amblyopic eye. Minimal interocular difference produced binocular summation, the magnitude of which decreased as the difference between the two eyes increased. Further increases in the monocular difference produced binocular inhibition. Anisometropic amblyopes showed a greater degree of binocular summation at low spatial frequencies compared to strabismic amblyopes. Both types of amblyopes showed binocular inhibition at high spatial frequencies. Clinical implications of binocular summation and inhibition in amblyopia are discussed.     

Contour integration in amblyopic monkeys

Amblyopia is characterized by losses in a variety of aspects of spatial vision, such as acuity and contrast sensitivity. Our goal was to learn whether those basic spatial deficits lead to impaired global perceptual processing in strabismic and anisometropic amblyopia. This question is unresolved by the current human psychophysical literature. We studied contour integration and contrast sensitivity in amblyopic monkeys. We found deficient contour integration in anisometropic as well as strabismic amblyopic monkeys. Some animals showed poor contour integration in the fellow eye as well as in the amblyopic eye. Orientation jitter of the elements in the contour systematically decreased contour-detection ability for control and fellow eyes, but had less effect on amblyopic eyes. The deficits were not clearly related to basic losses in contrast sensitivity and acuity for either type of amblyopia. We conclude that abnormal contour integration in amblyopes reflects disruption of mechanisms that are different from those that determine acuity and contrast sensitivity, and are likely to be central to V1.     

The effect of flankers on three tasks in central, peripheral, and amblyopic vision

Using identical stimuli and methods, we assessed the effects of flankers on three different tasks, orientation discrimination, contrast discrimination, and detection, in central, peripheral, and amblyopic vision. The goal was to understand the factors that limit performance of a task in the presence of flankers in each of these visual systems. The results demonstrate that: (1) For unflanked targets, the losses in peripheral and amblyopic vision (relative to the normal fovea) are ordered, with the loss of unflanked contrast discrimination thresholds considerably smaller than those for either detection or orientation discrimination. (2) For flanked targets, in normal foveal vision and anisometropic amblyopia, the critical distance is more or less proportional to the target size, whereas in peripheral and strabismic amblyopic vision, the critical distance shows much less (or no) dependence on target size. (3) For the normal fovea, and anisometropic amblyopia, when the target is large (>≈0.2 deg) the amount of threshold elevation induced by flankers is low, increasing when the target is very small. On the other hand, for the periphery and the amblyopic eyes of most strabismic amblyopes, the elevation is large over the range of sizes tested. (4) In peripheral and strabismic amblyopic vision, remote flankers elevate orientation discrimination and contrast discrimination thresholds but not detection thresholds. Our results show clearly that the effects of flanks depend on both the task and the type of visual system. We conclude that in normal foveal vision and anisometropic amblyopia, the effects of flankers largely reflects a reduction in visibility and may be explained by masking. On the other hand, in peripheral vision and strabismic amblyopia, the effects of flankers on orientation discrimination and to a lesser extent contrast discrimination cannot be explained by simple masking and are due to crowding.     

Suprathreshold spatial frequency detection and binocular interaction in strabismic and anisometropic amblyopia.

We have investigated suprathreshold contrast sensitivity and binocular interactions in strabismic and anisometropic amblyopes using a reaction time paradigm. For every spatial frequency, reaction time increased as the grating contrast decreased. At all spatial frequencies and contrast values the reaction times using the amblyopic eye were prolonged compared to the nonamblyopic eye, but most markedly at high spatial frequencies. In the middle range of spatial frequencies, the contrast vs. reaction time function for the nonamblyopic eyes was biphasic, suggesting that two separate mechanisms detect gratings at high and low contrast levels. These functions in deep amblyopia were monotonic, and in shallow amblyopia the break in the functions was present but shifted to lower contrast levels. Binocular interaction experiments showed that binocular summation was absent at all contrast levels, but binocular occlusion was evident at high contrast levels for amblyopic observers.     

CSF interocular interactions in childhood ambylopia

Contrast sensitivity functions (CSF's) were measured in the amblyopic and dominant eyes of 17 strabismic and 28 anisometropic children and in 19 similar age normal controls. A three-alternative forced-choice procedure was used to measure CSF's with the VCTS 6500. The results revealed reduced contrast sensitivity (CS) in both the amblyopic and dominant eyes of strabismic and anisometropic amblyopes compared to normal controls. Statistically significant intereye correlations of CS at each spatial frequency were found in all groups and in the presence of deep amblyopia, suggesting continued interocular interactions and binocularity. A separate longitudinal study of 7 of the amblyopes showed that, during the course of occlusion therapy, both the amblyopic and the dominant eyes improved in CSF. The results suggest that the amblyopic eye may influence CS in the dominant eye through interocular interactions. This process may serve to minimize CSF differences between the eyes and maximize binocular vision.     

Vernier acuity, crowding and amblyopia

When a vernier target is flanked by a pair of optimally positioned flanks, offset discrimination is strongly degraded. Spatial interference with vernier acuity was studied in each eye of observers with unilateral amblyopia associated with strabismus, anisometropia or both, and were compared to the functions obtained in the normal periphery (Levi et al., 1985). The results showed that: (1) For both strabismic and anisometropic amblyopes, as in normal central and peripheral vision, the extent of spatial interference was proportional to the unflanked vernier threshold. (2) For anisometropic amblyopes, grating and vernier acuity are affected similarly. (3) For strabismic amblyopes, like the normal periphery, vernier and grating acuity are decoupled, with vernier falling off faster than grating acuity. (4) The preferred eyes of strabismic but not anisometropic amblyopes have poorer vernier acuity than the normal controls. A conceptual framework for amblyopia based upon spatial filtering and spatial sampling is discussed.     

Detecting disorder in spatial vision

In normal foveal vision, visual space is accurately mapped from retina to cortex. However, the normal periphery, and the central field of strabismic amblyopes have elevated position discrimination thresholds, which have often been ascribed to increased 'intrinsic' spatial disorder. In the present study we evaluated the sensitivity of the human visual system (both normal and amblyopic) to spatial disorder, and asked whether there is increased 'intrinsic' topographical disorder in the amblyopic visual system. Specifically, we measured thresholds for detecting disorder (two-dimensional Gaussian position perturbations) either in a horizontal string of N equally spaced samples (Gabor patches), or in a ring of equally spaced samples over a wide range of feature separations. We also estimated both the 'equivalent intrinsic spatial disorder' and sampling efficiency using an equivalent noise approach. Our results suggest that both thresholds for detecting disorder, and equivalent intrinsic disorder depend strongly on separation, and are modestly increased in strabismic amblyopes. Strabismic amblyopes also show markedly reduced sampling efficiency. However, neither amblyopic nor peripheral vision performs like ideal or human observers with added separation-independent positional noise. Rather, the strong separation dependence suggests that the 'equivalent intrinsic disorder' may not reflect topographic disorder at all, but rather may reflect an abnormality in the amblyopes' Weber relationship.     

Spatial vision deficit underlies poor sine-wave motion direction discrimination in anisometropic amblyopia

For five anisometropic amblyopes and five normal controls, contrast sensitivities in both grating motion direction discrimination and moving grating detection were measured with the same moving sine-wave stimuli over a wide range of spatial and temporal frequencies. We found that the apparent local motion deficits in anisometropic amblyopia can be almost completely accounted for by deficits in moving grating detection. Furthermore, the differences between the amblyopic and the nonamblyopic eyes are nonspecific to temporal frequency in both motion direction discrimination and moving grating detection and are quantitatively identical to the differences in their contrast sensitivities. The observations on motion direction discrimination and its relationship to the contrast sensitivity function were replicated with an additional five anisometropic amblyopes and four normal controls. Complementing an earlier study on strabismic amblyopia (R. F. Hess & S. J. Anderson, 1993), these results suggest that local motion-sensitive mechanisms are largely intact in anisometropic amblyopia; the apparent local motion deficits in anisometropic amblyopia can be modeled with deficits in contrast sensitivity functions.     

Cerebral correlates of impaired grating perception in individual, psychophysically assessed human amblyopes

We investigated neuronal correlates of amblyopic deficits resulting from early onset strabismus or anisometropia by monitoring individual responses in retinotopically mapped cortical visual areas with functional magnetic resonance imaging (fMRI) in eight psychophysically assessed adult amblyopes. In lower visual areas (V1/V2), grating stimuli presented to the normal and the amblyopic eye evoked strong cortical responses, while responses to the amblyopic eye were progressively reduced in higher areas on the central visual pathway (V3a/VP; V4/V8; lateral occipital complex, LOC). Selective reduction for high spatial frequency gratings was especially obvious in LOC. This suggests that transmission of activity from the amblyopic eye is increasingly impaired while it is relayed towards higher processing levels. Elevated responses in parts of areas V1 and V2 to monocular stimulation of the amblyopic eye might be related to the spatial and temporal distortions experienced by some amblyopic subjects.     

Pupillary function in human amblyopia

Quantitative measurements of pupillary function (response amplitude and latency) were made for normal eyes and For normal and fellow amblyopic eyes of groups of strabismic and anisometropic amblyopes. Stimuli consisted of luminance modulation of a large, evenly lit area (pupil light reflex) as well as contrast modulation of sinusoidal gratings (pupil grating response) of fixed, space-averaged luminance. Measurements were made of the direct and the consensual reflex under monocular stimulation. A comparison of the amplitude of the pupil light reflex as a function of luminance modulation showed no significant differences between normal and fellow amblyopic eyes for both the strabismic and anisometropic groups of amblyopes studied. A similar comparison of the associated response latencies showed significant difference between normal and fellow amblyopic eyes for both groups. In general, reductions in response amplitude and latency of (he pupil grating response were found in individuals from each group when comparing the good and the affected eyes, although the observed group differences were only significant in the strabismic group. Interestingly, statistically significant reductions in both amplitude and latency for both the pupil light reflex and the pupil grating response were found between the eyes of normal observers and the so-called normal eyes of amblyopes in both groups studied. These results suggest that the type of pupillary deficit in amblyopia is a complicated one, depending not only on the type of amblyopia (strabismic or anisometropic) and the type of stimulus employed (light or pattern), but also on the parameter assessed (amplitude or latency) and whether the amblyopic result is referenced to its fellow normal eye or to the normal eye of a non-amblyopic observer- Since the pupil response to light flux changes is not mediated exclusively via the retinal projection to the midbrain and may also involve the activity of central visual pathways, the results obtained in this study cannot be used to provide definitive evidence for the site of abnormality in amblyopia.     

BOLD fMRI and DTI in strabismic amblyopes following occlusion therapy

Evaluation of brain cluster activation using the functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) was sought in strabismic amblyopes. In this hospital-based case–control cross-sectional study, fMRI and DTI were conducted in strabismic amblyopes before initiation of any therapy and after visual recovery following the administration of occlusion therapy. FMRI was performed in 10 strabismic amblyopic subjects (baseline group) and in 5 left strabismic amblyopic children post-occlusion therapy after two-line visual improvement. Ten age-matched healthy children with right ocular dominance formed control group. Structural and functional MRI was carried out on 1.5T MR scanner. The visual task consisted of 8 Hz flickering checkerboard with red dot and occasional green dot. Blood-oxygen-level-dependent (BOLD) fMRI was analyzed using statistical parametric mapping and DTI on NordicIce (NordicNeuroLab) softwares. Reduced occipital activation was elicited when viewing with the amblyopic eye in amblyopes. An ‘ipsilateral to viewing eye’ pattern of calcarine BOLD activation was observed in controls and left amblyopes. Activation of cortical areas associated with visual processing differed in relation to the viewing eye. Following visual recovery on occlusion therapy, enhanced activity in bilateral hemispheres in striate as well as extrastriate regions when viewing with either eye was seen. Improvement in visual acuity following occlusion therapy correlates with hemodynamic activity in amblyopes.     

Assessment of cortical dysfunction in human strabismic amblyopia using magnetoencephalography (MEG).

The aim of this study was to use the technique of magnetoencephalography (MEG) to determine the effects of strabismic amblyopia on the processing of spatial information within the occipital cortex of humans. We recorded evoked magnetic responses to the onset of a chromatic (red/green) sinusoidal grating of periodicity 0.5-4.0 c deg-1 using a 19-channel SQUID-based neuromagnetometer. Evoked responses were recorded monocularly on six amblyopes and six normally-sighted controls, the stimuli being positioned near the fovea in the lower right visual field of each observer. For comparison, the spatial contrast sensitivity function (CSF) for the detection of chromatic gratings was measured for one amblyope and one control using a two alternate forced-choice psychophysical procedure. We chose red/green sinusoids as our stimuli because they evoke strong magnetic responses from the occipital cortex in adult humans (Fylan, Holliday, Singh, Anderson & Harding. (1997). Neuroimage, 6, 47-57). Magnetic field strength was plotted as a function of stimulus spatial frequency for each eye of each subject. Interocular differences were only evident within the amblyopic group: for stimuli of 1-2 c deg-1, the evoked responses had significantly longer latencies and reduced amplitudes through the amblyopic eye (P < 0.05). Importantly, the extent of the deficit was uncorrelated with either Snellen acuity or contrast sensitivity. Localization of the evoked responses was performed using a single equivalent current dipole model. Source localizations, for both normal and amblyopic subjects, were consistent with neural activity at the occipital pole near the V1/V2 border. We conclude that MEG is sensitive to the deficit in cortical processing associated with human amblyopia, and can be used to make quantitative neurophysiological measurements. The nature of the cortical deficit is discussed.     

Two-dimensional spatial distortions in human strabismic amblyopia

Two-dimensional space perception was measured in the central visual field of amblyopic subjects under special consideration of spatial distortions and spatial uncertainty. The subjects had to construct circles with different radii around a given fixation point. Subjects with deep strabismic amblyopia were showed to exhibit considerable distortion in the amblyopic eye. Each subject exhibited an individual distortion pattern. The dominant eye showed distortions similar to those seen in normal observers. Subjects with mild strabismic amblyopia, strabismic alternators and anisometropic amblyopes did not exhibit any significant spatial distortions. Data from dichoptic localization experiments indicate that anomalous retinal correspondence might contribute to monocular spatial distortions.     

Differential changes of magnocellular and parvocellular visual function in early- and late-onset strabismic amblyopia

PURPOSE: Studies in nonhuman primates show that monocular visual deprivation starting at different ages has different effects on cells in the parvocellular and magnocellular laminae of the lateral geniculate nucleus. The present study used color and luminance contrast sensitivity (CS) measurements to look for differences in parvocellular- and magnocellular-related visual function in human subjects with strabismic amblyopia. METHODS: Fifteen subjects with early- and 14 with late-onset strabismic amblyopia and similar ranges of visual acuity were studied, together with 15 subjects with normal vision. Contrast sensitivities were measured to an equiluminant (L-M cone-modulated) grating with slow onset and an achromatic (L+M cone-modulated) 0.8-cpd grating with rapid onset using an adaptive METHOD: RESULTS: Luminance and color CS were lower in the amblyopic eyes than in the fellow eyes of all amblyopes. For luminance CS, this was due both to an increase in sensitivity of the fellow eye and to a reduction in sensitivity in the amblyopic eye. Color CS was greatly reduced in the amblyopic and fellow eyes of subjects with strabismic amblyopia of early- and late onset compared with subjects with normal vision. The reduction in color CS compared with luminance CS was significantly greater in eyes with late- rather than early-onset amblyopia. CONCLUSIONS: Parvocellular and magnocellular function are differentially affected in the amblyopic and fellow eyes of subjects with strabismic amblyopia. The difference is more marked in late-onset amblyopia than in early-onset amblyopia.