The visually evoked potential in humans with amblyopia: Pseudorandom modulation of uniform field and sine-wave gratings

Summary The visually evoked potential was recorded in response to pseudorandom modulation of a uniform field and sine-wave gratings in humans with naturally occurring amblyopia. Analysis in the frequency domain showed similar temporal tuning when the nonamblyopic and amblyopic eye were stimulated with a uniform field and with spatial stimuli. Although most observers showed some reduction in the cortical response to stimulation of the amblyopic eye with uniform field modulation, all observers showed reductions in the response obtained for stimulation of the amblyopic eye with spatial stimuli. This decrease in the cortical response to stimulation of the amblyopic eye for sine-wave gratings was present at either the low and middle temporal frequencies or over the range of temporal frequencies tested, and was greater than that observed in those amblyopes who also showed reductions with uniform field modulation. Latency measures in the time domain showed increases in the response of the early components when the amblyopic eye was stimulated with a uniform field and with sine-wave gratings above 2 c/deg. These electrophysiological results confirm the results obtained psychophysically which suggest that although amblyopia is primarily a spatial anomaly, the response is influenced by the temporal attributes of the stimulus as well.Supported by grant ROI EYO1728 from the National Eye Institute, National Institutes of Health, Bethesda, Maryland     

Mesopic contrast sensitivity functions in amblyopic children

This study both measured and compared the mesopic contrast sensitivity function and the visual acuity in both normal and amblyopic eyes from amblyopic children using an ACV (visual acuity analyzer). Twenty one amblyopic children (mean age, 8.48 years; S.D., 1.68 years), 11 strabismic amblyopes and 10 anisometropic amblyopes, were tested. Based on a display of the standard optotypes, the minimal contrast level, at which the optotypes were correctly read for all sizes of displays from a distance of 1m, was measured. The contrast ranged from 1% to 99% and the spatial frequencies ranged from 0.6 to- 30cpd using a Landolt ring composed of low (0.6- 2.9 c.p.d.), intermediate (3.0 - 12.9 c.p.d.) and high level (13.0- 30.0 c.p.d.) frequencies. As the visual acuity decreased, the mesopic contrast sensitivity function decreased along the contrast sensitivity axis. However, the peak sensitivity was noted at the same spatial frequencies. A comparison between the normal eye and the corresponding amblyopic eye showed that under mesopic conditions, the contrast sensitivity functions decreased more in the intermediate spatial frequencies than in the other spatial frequencies. The mesopic contrast sensitivity function decreased in the amblyopic eyes, which suggests the possibility of its use an adjunct to an evaluation of amblyopia.     

The dependence of binocular contrast sensitivities on binocular single vision in normal and amblyopic human subjects

We have measured monocular and binocular contrast sensitivities in response to medium to high spatial frequencies of vertical sinusoidal grating patterns in normal subjects, anisometropic amblyopes, strabismic amblyopes and non-amblyopic esotropes. On binocular viewing, contrast sensitivities were slightly but significantly increased in normal subjects, markedly increased in anisometropes and esotropes with anomalous binocular single vision (BSV) and significantly reduced in esotropes and exotropes without BSV. Application of a prismatic correction to the strabismic eye in order to achieve bifoveal stimulation resulted in a significant reduction in contrast sensitivity in esotropes with and without anomalous BSV, in exotropes and in non-amblyopic esotropes. Control experiments in normal subjects with monocular viewing showed that degradative effects of the prism occurred only with high prism powers and at high spatial frequencies, thus establishing that the reduced contrast sensitivities were the consequence of bifoveal stimulation rather than optical degradation. Displacement of the image of the grating pattern by 2 deg in normal subjects and anisometropes by a dichoptic method to simulate a small angle esotropia had no effect on the contrast sensitivities recorded through the companion eye. By contrast, esotropes showed similar reductions in contrast sensitivity to those obtained with the prism experiments, confirming a fundamental difference between subjects with normal and abnormal ocular alignments. The results have thus established a suppressive action of the fovea of the amblyopic eye acting on the companion, non-amblyopic eye and indicate that correction of ocular misalignments in adult esotropes may be disadvantageous to binocular visual performance.     

Neural site of strabismic amblyopia in cats: spatial frequency deficit in primary cortical neurons

Summary The acuities of cells in the primary visual cortex of five tenotomized strabismic cats were measured. Previous behavioural studies have shown such animals to possess a severe amblyopia of approximately 1.5 octaves of spatial frequency, yet the acuities of both retinal ganglion and lateral geniculate X-cells are normal. The receptive fields of the cortical cells sampled were within 5° of the area centralis projection. On average, the acuities of cortical cells driven by the amblyopic eye were nearly 1 octave less than those for the non-deviating eye. However, the best cell acuities for each eye were nearly the same. The relationship between ocular dominance and cell acuity was found to be different for the two eyes despite a symmetrical ocular dominance distribution. The acuity deficit for cells driven through the amblyopic eye was present at all depths along the electrode tracks. We conclude that in this model amblyopia, the initial spatial processing deficit lies in the visual cortex, and most probably in the cells of layer IV. Further-more, the presence of a few cells driven by the amblyopic eye which can perform nearly as well as those from the fellow eye in processing high spatial frequencies gives new insight into the way in which strabismic and deprivation amblyopias differ.     

Relationship of visual cortex function and visual acuity in anisometropic amblyopic children

Purpose: To detect the functional deficit of the visual cortex in anisometropic amblyopia children using functional magnetic resonance imaging (fMRI) technique, and investigate the relationship between visual acuity and visual cortex function.Methods: Blood oxygenation level-dependent fMRI (BOLD-fMRI) was performed in ten monocular anisometropic amblyopia children and ten normal controls. fMRI images were acquired in two runs with visual stimulation delivered separately through the sound and amblyopic eyes. Measurements were performed in cortical activation of striate and extrastriate areas at the occipital lobe. The relationship between cortex function and visual acuity was analyzed by Pearson partial analysis.Results: The activation areas of both the striate and extrastriate cortices in the amblyopic eyes were significantly lower than that of the sound fellow eyes. No relationship was found between the striate and extrastriate cortex activation. No relationship was found between the visual cortical activation of striate, extrastriate areas and visual acuity of anisometropic amblyopes.Conclusions: BOLD-fMRI revealed the independent striate and extrastriate cortical deficits in anisometropic amblyopes. In addition, the visual acuity lesion and the striate and extrastriate cortical deficits were not parallel, and results of fMRI examination have much potential value in the evaluation of amblyopia.     

Contrast sensitivity function of sound eye after occlusion therapy in the amblyopic children

To verify the changes of mesopic and photopic contrast sensitivity function of sound eye whose visual acuity was kept the same after occlusion therapy in the amblyopic children. Fourteen sound eyes of amblyopic children (mean; 7.67 years; S.D., 1.50 years) who kept their visual acuity the same after the occlusion therapy were tested. The children had 6 hours of part-time patch therapy for 3 months prior to this examination. Among 14 amblyopic children, 8 were anisometric and 6 were strabismic amblyopes. Using the visual capacity analyzer which measures the minimal contrast level at from low to high spatial frequencies, the contrast sensitivity of sound eye was measured, under both photopic and mesopic condition, before and after 3 months of occlusion therapy. Comparing the contrast sensitivity of sound eye after the occlusion therapy to that before the occlusion, there was no statistical difference in photopic condition. When it comes to mesopic condition, the contrast sensitivity decreased at the intermediate spatial frequency level (3-13 c.p.d, p=0.028) after the occlusion therapy. The occlusion caused statistically significant decrease in mesopic contrast sensitivity, when the visual acuity was not changed after the occlusion therapy. It may indicate that mesopic contrast sensitivity can be considered as a useful tool for early detection of hidden occlusion amblyopia.     

Attention activates winner-take-all competition among visual filters

Shifting attention away from a visual stimulus reduces, but does not abolish, visual discrimination performance. This residual vision with 'poor' attention can be compared to normal vision with 'full' attention to reveal how attention alters visual perception. We report large differences between residual and normal visual thresholds for discriminating the orientation or spatial frequency of simple patterns, and smaller differences for discriminating contrast. A computational model, in which attention activates a winner-take-all competition among overlapping visual filters, quantitatively accounts for all observations. Our model predicts that the effects of attention on visual cortical neurons include increased contrast gain as well as sharper tuning to orientation and spatial frequency.     

Amblyopia occurs in retinal ganglion cells in cats reared with convergent squint without alternating fixation

Summary The spatial resolving power, contrast sensitivity, and receptive field properties of retinal ganglion cells were studied in cats reared with either convergent or divergent squint in one eye. Sustained-X cells in the area centralis of the squinting eye of the cats with esotropia without alternating fixation showed significantly poorer spatial resolution, and reduced contrast sensitivity compared with cells in the area centralis of the normal eye. These amblyopic sustained-X cells in the area centralis of the squinting eye had receptive field characteristics similar to those found in immature cells of young kittens. They had a shallow sensitivity gradient within a relatively widespread centre zone and a weak and widespread inhibitory surround. In contrast, the sustained cells in the area centralis of the normal eye revealed a typical, well defined, small centre zone with its sensitivity gradient extremely steep and its inhibitory surround strong and confined. A minor degree of amblyopia was also found in transient Y-cells in the area centralis of the squinting eye of these cats.However, no loss of resolving power was found in the cells in the area centralis of the squinting eye of the cats with esotropia or exotropia which showed alternating fixation. Thus, amblyopia occurs in those eyes which have lost the use of the area centralis as the normal visual axis during early postnatal development, and its organic lesion is already apparent in the retinal ganglion cells — the third order neurone in the afferent visual system. It is suggested that the loss of the ability to fixate results in inadequate stimulation of the central retinal ganglion cells due to the habitual presence of blurred images at the area centralis which prevents their full development during the critical period.This work was supported by grants from MRC and St. Thomas's Hospital to H. Ikeda     

Cortical effects of brief daily periods of unrestricted vision during early monocular form deprivation

Experiencing daily brief periods of unrestricted vision during early monocular form deprivation prevents or reduces the degree of resulting amblyopia. To gain insight into the neural basis for these "protective" effects, we analyzed the monocular and binocular response properties of individual neurons in the primary visual cortex (V1) of macaque monkeys that received intermittent unrestricted vision. Microelectrode-recording experiments revealed significant decreases in the proportion of units that were dominated by the treated eyes, and the magnitude of this ocular dominance imbalance was correlated with the degree of amblyopia. The sensitivity of V1 neurons to interocular spatial phase disparity was significantly reduced in all treated monkeys compared with normal adults. With unrestricted vision, however, there was a small but significant increase in overall disparity sensitivity. Binocular suppression was prevalent in monkeys with constant form deprivation but significantly reduced by the daily periods of unrestricted vision. If neurons exhibited consistent responses to stimulation of the treated eye, monocular response properties obtained by stimulation of the two eyes were similar. These results suggest that the observed protective effects of brief periods of unrestricted vision are closely associated with the ability of V1 neurons to maintain their functional connections from the deprived eye and that interocular suppression in V1 may play an important role in regulating synaptic plasticity of these monkeys.     

Behavioural studies of spatial vision in cats reared with convergent squint: Is amblyopia due to arrest of development?

Summary Visual acuity and contrast sensitivity were measured behaviourally in normal adult cats and cats reared with monocular convergent squint from 3, 6, 8, 12, and 24 weeks of age. The visual acuity of the squinting eye was significantly lower than that of the non-squinting eye in cats with squint from 3, 6, and 8 weeks of age. No significant difference in acuity between eyes was found in the 12- and 24-week squinting cats and in the controls.Contrast thresholds at all spatial frequencies tested (range 0.13–2.0 c/ °) were higher in the squinting eye than in the non-squinting eye of cats with squint from 3 and 6 weeks of age, but differences were greater at the higher spatial frequencies. In the 8-week squinting cat, contrast thresholds were increased only at higher spatial frequencies. No significant differences in contrast sensitivity were found in the cat with squint from 24 weeks of age and in the controls.The degree of disturbance of spatial vision in squinting cats was most related to the age at onset of the squint, i.e., the earlier the onset, the more profound the amblyopia. The period of susceptibility extended from about 3 to 12 weeks of age. When compared with data on the development of visual acuity in kittens, the pattern of results from the present study suggests that convergent squint can arrest the development of spatial vision.This work was supported by the M. R. C.     

Edge sensitive mechanisms in humans with abnormal visual experience

Summary Detection of broadband, aperiodic stimuli (edges) was investigated in normal observers, and in observers with abnormal visual experience which resulted in amblyopia. The spatial properties of the mechanisms used to detect an edge were investigated by a method of subthreshold addition. The method involved the determination of the threshold contrast for detecting an edge in the presence of a subthreshold line at various distances from the edge. In normal eyes, the one dimensional sensitivity profile of the edge detecting mechanism was: (1) approximately antisymmetric, (2) very localized, with sensitivity changes restricted to ±6'–8' on either side of the edge, and (3) phase dependent, showing an abrupt change in sign between ±1.5'. The sensitivity profiles of the amblyopic eyes were also approximately antisymmetric and showed the same steep rate of change from plus to minus as the fellow (nonamblyopic) eyes. However, in every case, the spatial extent of the profile was much broader than that of the nonamblyopic eyes. In normal eyes, the narrowest edge sensitivity profile was associated with the fovea; however, in two amblyopes with eccentric fixation, the narrowest edge sensitivity profile coincided with the locus of eccentric fixation. Moreover, the grating sensitivity function of the edge detecting mechanism of the amblyopic eye was similar to that of the non-amblyopic eye, but was shifted toward lower spatial frequencies. Control experiments show that these results are not accounted for on the basis of optics, eccentric fixation, or abnormal eye movements. The findings are discussed in terms of current models for the detection of aperiodic stimuli, and in the context of animal models of amblyopia.This work was supported by Research Grants from the National Eye Institute (Bethesda, Md.) R01EY01278 and R01EY01139     

Undercounting features and missing features: evidence for a high-level deficit in strabismic amblyopia

Abnormal visual development in strabismic amblyopia drastically affects visual perception and properties of neurons in primary visual cortex (V1). To test the notion that amblyopia also has consequences for higher visual areas, we asked humans with amblyopia to count briefly presented features. Using the amblyopic eye, strabismic amblyopes counted inaccurately, markedly underestimating the number of features. This inaccuracy was not due to low-level considerations (blur, visibility, crowding, undersampling or topographical jitter), as they also underestimated the number of features missing from a uniform grid. Rather, counting deficits in strabismic amblyopes reflected a higher-level limitation in the number of features the amblyopic visual system can individuate.     

From motor cortex to visual cortex: the application of noninvasive brain stimulation to amblyopia

Noninvasive brain stimulation is a technique for inducing changes in the excitability of discrete neural populations in the human brain. A current model of the underlying pathological processes contributing to the loss of motor function after stroke has motivated a number of research groups to investigate the potential therapeutic application of brain stimulation to stroke rehabilitation. The loss of motor function is modeled as resulting from a combination of reduced excitability in the lesioned motor cortex and an increased inhibitory drive from the nonlesioned hemisphere over the lesioned hemisphere. This combination of impaired neural function and pathological suppression resonates with current views on the cause of the visual impairment in amblyopia. Here, we discuss how the rationale for using noninvasive brain stimulation in stroke rehabilitation can be applied to amblyopia, review a proof-of-principle study demonstrating that brain stimulation can temporarily improve amblyopic eye function, and propose future research avenues.     

基于低频振幅算法的屈光参差性弱视自发脑活动研究

目的基于低频振幅(amplitude of low frequency fluctuation,ALFF)算法分析屈光参差性弱视和正常对照组的功能性磁共振成像(functional magnetic resonance imaging,f MRI)图像数据,对比揭示弱视患者脑部自发活动的异常,以及这些异常与弱视视力损失的相关性。方法在闭眼静息条件下采集22例弱视成年人和21例正常对照组f MRI数据,对f MRI数据进行预处理,计算每个被试脑区的ALFF值。应用双样本t检验对ALFF结果进行组间分析,采用皮尔森分析弱视不同脑区的ALFF与其损伤的相关程度。结果在屈光参差性成人弱视与正常组有显著性差异的脑区中,脑部自发活动增加的脑区主要分布在颞下回、颞上回、枕叶等区域,脑部自发活动降低的脑区主要分别在小脑后叶、额下回、额上回等区域。首次发现小脑后叶、楔回、枕叶、颞上回和额叶等区域脑区自发活动与弱视损伤有显著相关性。结论基于低频振幅的静息态磁共振分析是有效的非侵入式脑区同步性异常研究方法,能够反映屈光参差性弱视自发脑部活动脑区异常表现,这些同步性异常表现与视力损失程度有较强的相关性,这些结果对于弱视致病机制模型研究和提出新的治疗方法都有重要启发。     

Visual acuity in the blue cone monochromat

1. To isolate the blue cones of the normal eye, blue sine-wave gratings were superimposed on a bright yellow background. Threshold contrasts for resolution of the gratings were then determined.2. Under these conditions visual acuity for high contrast gratings on four normal subjects was on the average 0.31 min(-1). This is about a factor of 6 lower than grating acuity under optimal conditions.3. The contrast sensitivity of two subjects who lack the normal red and green receptor mechanisms was measured using blue sinusoidally modulated gratings. Visual acuity was found to be greatly reduced from normal. The low acuity of these individuals is due to both a reduction in contrast sensitivity and a reduction in resolution.4. The spatial resolving characteristics of these subjects resembles the vision of the normal eye under conditions which isolate the blue sensitive mechanisms.5. The vision of the cone monochromat differs significantly from that of the more typical rod monochromat. The rod monochromat has even lower acuity than the blue cone monochromat for high contrast gratings but has much greater contrast sensitivity for gratings of low spatial frequency.     

Binocularity and spatial frequency dependence of calcarine activation in two types of amblyopia

OBJECTIVE AND BACKGROUND: Strabismus and anisometropia early in life frequently causes monocular amblyopia. Activation of the visual cortex is compared between the two types of amblyopia to elucidate differences in the pathogenetic mechanism of the disease. METHODS: Using an EPI gradient echo sequence in 1.5T MRI, calcarine activation by monocular viewing of checkerboard patterns with reversal was examined in terms of binocularity of the activation and dependence on the spatial frequency of the stimuli. RESULTS: First, the proportion of voxels activated by both normal and amblyopic eye monocular stimulations is lower in the strabismic group than in the anisometropic group. Second, the activation by higher-spatial-frequency stimuli is reduced in the anisometropic group, but not in the strabismic group. CONCLUSIONS: These findings from the human visual cortex are consistent with the view proposed based on animal research that the loss of binocular interaction and the undersampling of high-spatial-frequency components of visual stimuli are each one of the underlying changes in strabismic and anisometropic amblyopia, respectively.     

Binocular deficits associated with early alternating monocular defocus. I. Behavioral observations

To study the binocular vision deficits associated with anisometropia, monkeys were reared with alternating monocular defocus, which allowed monocular mechanisms to develop normally while binocular mechanisms were selectively compromised. A defocusing contact lens of -1.5 D, -3 D, or -6 D was worn on alternate eyes on successive days (n = 3 per lens power) from 3 wk to 9 mo of age. The control subjects were two normally reared monkeys and two human observers. Functional binocular vision was assessed through behavioral measurements of stereoscopic depth discrimination thresholds as a function of spatial frequency. To characterize the extent of the deficits in disparity processing at a given spatial frequency, the contrast required to support stereopsis was determined for a range of disparities that exceeded the subjects' measured stereoacuity. The lens-reared monkeys showed spatial-frequency-selective deficits in stereopsis that depended on the magnitude of the simulated anisometropia experienced during the rearing period. For a given spatial frequency, the treated monkeys generally required higher than normal contrasts to support stereopsis even for large disparities. Moreover, a given increase in contrast produced smaller than normal improvements in stereo discrimination in our treated subjects, which suggests that in addition to deficits in contrast sensitivity, disparity-sensitive mechanisms exhibited low contrast gains. The spatial-frequency selective nature of the binocular deficits produced by the imposed anisometropia indicate that disparity processing mechanisms are normally spatial-frequency selective and that mechanisms tuned to different spatial frequencies can be differentially affected by abnormal binocular visual experience.     

Compound grating discrimination in extrafoveal and amblyopic vision

Compound grating discrimination was measured in normal foveal and extrafoveal vision as well as in central vision of amblyopic subjects. Two types of discrimination were examined: 0 degrees versus 180 degrees and 90 degrees versus 270 degrees phase shift of the second harmonic relative to the fundamental. In common with several previous studies, we found that both 0/180 and 90/270 discriminations are possible in extrafoveal vision. However, we show that differences in foveal and extrafoveal sensitivity can be eliminated for both types of discrimination by scaling the stimulus size appropriately. The extent of spatial magnification necessary to equate foveal and extrafoveal performance differed markedly, with 90/270 discriminations requiring much more magnification. In the amblyopic subjects, the magnitude of the 90/270 deficit was greater than the 0/180 deficit in all six amblyopes tested. In common with previous investigations, we suggest that the visual system adopts a discrimination strategy, based upon differences in local features, between the patterns to be discriminated. One process registers positional relationships, while a second process registers local contrast differences. In this context, the reduced ability of the normal periphery and amblyopic fovea to perform mirror-symmetric discriminations is explained in terms of losses in positional acuity.     

Eye dominance predicts fMRI signals in human retinotopic cortex

There have been many attempts to define eye dominance in normal subjects, but limited consensus exists, and relevant physiological data is scarce. In this study, we consider two different behavioral methods for assignment of eye dominance, and how well they predict fMRI signals evoked by monocular stimulation. Sighting eye dominance was assessed with two standard tests, the Porta Test, and a 'hole in hand' variation of the Miles Test. Acuity dominance was tested with a standard eye chart and with a computerized test of grating acuity. We found limited agreement between the sighting and acuity methods for assigning dominance in our individual subjects. We then compared the fMRI response generated by dominant eye stimulation to that generated by non-dominant eye, according to both methods, in 7 normal subjects. The stimulus consisted of a high contrast hemifield stimulus alternating with no stimulus in a blocked paradigm. In separate scans, we used standard techniques to label the borders of visual areas V1, V2, V3, VP, V4v, V3A, and MT. These regions of interest (ROIs) were used to analyze each visual area separately. We found that percent change in fMRI BOLD signal was stronger for the dominant eye as defined by the acuity method, and this effect was significant for areas located in the ventral occipital territory (V1v, V2v, VP, V4v). In contrast, assigning dominance based on sighting produced no significant interocular BOLD differences. We conclude that interocular BOLD differences in normal subjects exist, and may be predicted by acuity measures.     

Abnormal orientation selectivity in both eyes of strabismic amblyopes

Summary In normal observers preadaptation to a parallel grating increases the contrast threshold for a line whereas a perpendicular grating has no effect. Such orientation selectivity was not found in the amblyopic eye of two out of five squinters. Only a weak after-effect produced with a grating parallel to the line was obtained in the good eye of four of the amblyopes while all of them show an abnormal threshold reduction following adaptation to a perpendicular grating. This suggests a relationship between abnormal binocular interaction during visual development and the organization of orientational mechanisms but does not explain the loss of visual acuity in amblyopia.