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Biomedical subjects

R S Harwerth

Publications and source records attributed to R S Harwerth.

At least 19 recordsLinked to original sources

Stereopsis and disparity vergence in monkeys with subnormal binocular vision.

The surgical treatment for strabismus in infants generally results in microtropia or subnormal binocular vision. Although the clinical characteristics of these conditions are well established, there are important questions about the mechanisms of binocular vision in these patients that can best be investigated in an appropriate animal model. In the present psychophysical investigations, spatial frequency response functions for disparity-induced fusional vergence and for local stereopsis were studied in macaque monkeys, who demonstrated many of the major visual characteristics of patients whose eyes were surgically aligned during infancy. In six rhesus monkeys, unilateral esotropia was surgically induced at various ages (30-184 days of age). However, over the next 12 months, all of the monkeys recovered normal eye alignment. Behavioral measurements at 4-6 years of age showed that the monkeys' prism-induced fusional vergence responses were indistinguishable from those of control monkeys or humans with normal binocular vision. Investigations of stereo-depth discrimination demonstrated that each of the experimental monkeys also had stereoscopic vision, but their stereoacuities varied from being essentially normal to severely stereo-deficient. The degree of stereo-deficiency was not related to the age at which surgical esotropia was induced, or to the presence or absence of amblyopia, and was not dependent on the spatial frequency of the test stimulus. Altogether, these experiments demonstrate that a temporary, early esotropia can affect the binocular disparity responses of motor and sensory components of binocular vision differently, probably because of different sensitive periods of development for the two components.

Amblyopia

Residual binocular interactions in the striate cortex of monkeys reared with abnormal binocular vision.

We investigated the nature of residual binocular interactions in the striate cortex (V1) of monkey models for the two most common causes of visual dysfunction in young children, specifically anisometropia and strabismus. Infant rhesus monkeys were raised wearing either anisometropic spectacle lenses that optically defocused one eye or ophthalmic prisms that optically produced diplopia and binocular confusion. Earlier psychophysical investigations had demonstrated that all subjects exhibited permanent binocular vision deficits and, in some cases, amblyopia. When the monkeys were adults, the responses of individual V1 neurons were studied with the use of microelectrode recording techniques while the animals were anesthetized and paralyzed. The manner in which the signals from the two eyes were combined in individual cells was investigated by dichoptically stimulating both eyes simultaneously with drifting sine wave gratings. In both lens- and prism-reared monkeys, fewer neurons had balanced ocular dominances and greater numbers of neurons were excited by only one eye. However, many neurons that appeared to be monocular exhibited clear binocular interactions during dichoptic stimulation. For the surviving binocular neurons, the maximum binocular response amplitudes were lower than normal; fewer neurons, particularly complex cells, were sensitive to relative interocular spatial phase disparities; and the remaining disparity-sensitive neurons exhibited lower degrees of binocular interaction. In prism-reared monkeys, an unusually high proportion of complex cells exhibited binocular suppression during dichoptic stimulation. Binocular contrast summation experiments showed that for both cooperative and antagonistic binocular interactions, contrast signals from the two eyes were combined by individual neurons in a normal linear fashion in both lens- and prism-reared monkeys. The observed binocular deficits appear to reflect a reduction in functional inputs from one eye and/or spatial imprecision in the monocular receptive fields rather than an aberrant form of binocular interaction. In the prism-reared monkeys, the predominance of suppression suggests that inhibitory connections were, however, less susceptible to diplopia and confusion than excitatory connections. Overall, there were many parallels between V1 physiology in our monkey models and the residual vision of humans with anisometropia or strabismus.

Animals

Experimental glaucoma: perimetric field defects and intraocular pressure.

PURPOSE: To investigate the relationship between intraocular pressure (IOP) and the progression of visual field defects caused by experimental glaucoma in Macaca mulatta monkeys. METHODS: Perimetric fields were measured by behavioral methods in 18 rhesus monkeys during the course of unilateral glaucoma produced by argon laser treatment of the trabecular meshwork. The monkeys' IOPs were measured by applanation tonometry. Visual field defects were quantified by the mean deviation perimetric index from Humphrey Field Analyzer C24-2, model 630 (Humphrey Allergan, San Leandro, CA, U.S.A.), full-threshold data. RESULTS: The monkeys' eyes demonstrated considerable variability in their susceptibility to pressure-induced neural damage. For 10 of the monkeys, significant field defects were correlated with the increases in their IOPs and the defects progressed monotonically to end-state glaucoma. For the other monkeys, the mean deviation index was not well correlated with IOP; some eyes withstood pressures in excess of 35 mm Hg for several months before significant reduction in visual sensitivity. However, once they began, the rate of progression of field defects was similar across subjects. CONCLUSIONS: Laser ablation of the trabecular meshwork in monkeys provides a model for investigations of the effects of IOP that are not confounded by other ocular or visual disorders. Behavioral perimetry showed the same intersubject variability in the effects of elevated IOP on visual field sensitivities of monkeys that are common with high-tension glaucoma or ocular hypertension in patients. Thus, these investigations provide additional support for the use of the model for a wide variety of clinical investigations on glaucoma.

Animals

Loss of stereopsis in monkeys following prismatic binocular dissociation during infancy.

Prismatic binocular dissociation was used during infancy to mimic conditions of strabismus in macaque infants. Prisms worn continuously produce a diplopia unfavorable for the maintenance and development of the binocular visual system. Prism-reared monkeys were tested as young adults and found to be permanently stereoblind for dynamic random dot stereograms. Control monkeys did comparably to humans on such tests. It is concluded that short periods of diplopia attendant with strabismus are sufficient to produce permanent stereoblindness.

Age of Onset

Judgments by monkeys of apparent depth in dynamic random-dot stereograms.

Young macaques discriminated apparent depths of targets embedded in dynamic random dot stereograms; a test of stereopsis. In a 'same/different' paradigm, the discrimination took longer if the pair of stimuli appeared to be in same depth plane, than when they appeared to be located in a different depth plane. The decision time was an inverse function of the disparity difference. Apparent depth discrimination performance decreased as a function of disparity, with no differences in judgments regarding crossed or uncrossed disparities.

Animals

Binocularity in prism-reared monkeys.

Prismatic binocular dissociation in infant monkeys mimicked a concomitant squint. Within 3 weeks, the numbers of binocular neurons in the primary visual cortex were reduced by half and did not recover with up to 5 years of subsequent unrestricted binocular visual experience. The monkeys failed to show binocular summation for spatial contrast sensitivity tasks and were unable to utilise horizontal binocular disparities in random-dot stereograms-two indices of stereoblindness. Electrophysiological analysis of the V1 and V2 cortices showed a dramatic reduction in binocular neurons. Analysis of interocular spatial phase tuning functions showed a conspicuous loss of excitatory binocular drive in V1 neurons which was sufficient to account for many of the defects in binocular function.

Animals

Motor and sensory fusion in monkeys: psychophysical measurements.

Motor and sensory fusion, the basic processes of binocularity, must be present for bifoveal fixation with true fusion and stereopsis during ordinary viewing. The characteristics of motor and sensory fusion have been established for patients with normal and subnormal binocular vision; the present report describes our psychophysical studies of these processes in the macaque monkey. Three recent investigations of motor and sensory fusion in monkeys are described. The studies involved: (1) the comparability of motor and sensory fusion in monkeys and humans with normal binocular vision, (2) the effects of an early period of abnormal binocular vision on motor and sensory fusion in monkeys, and (3) the contrast sensitivity for binocular disparity in monkeys with stereo-deficiencies. The results of these studies demonstrated an excellent homology between the normal binocular vision of monkeys and humans. We also found that a period of esotropia during infancy caused deficiencies in sensory fusion, but not motor fusion. In some monkeys, the sensory deficiency persisted over the entire range of binocular disparities that were compatible with stereopsis, while other subjects demonstrated normal stereo-sensitivity for the largest fusible binocular disparities. The stereo-deficiencies of these monkeys, along with other visual attributes, suggest that their binocular vision is a viable model for the binocularity of patients with subnormal binocular vision or the monofixation syndrome.

Animals

The scotopic electroretinogram of macaque after retinal ganglion cell loss from experimental glaucoma.

PURPOSE: This study describes the dark-adapted electroretinograms (ERGs) of macaque monkeys with severe visual field defects and substantial retinal ganglion cell loss as a consequence of long-standing ocular hypertension. METHODS: Monocular experimental glaucoma was produced by argon laser trabeculoplasty, and visual fields were assessed with behavioral static perimetry. Electroretinographic responses to brief ganzfeld flashes under fully dark-adapted conditions were recorded using DTL fiber electrodes in anesthetized animals. The authors quantified retinal layer thickness and cell loss in 1-micron radial sections and inspected optic nervous under the light microscope. RESULTS: At the lowest intensities, a sensitive negative component of the scotopic ERG, which normally peaks approximately 200 msec after stimulus onset, was present in the control eyes but was reduced greatly or was virtually absent in the experimental eyes of monkeys with severe visual field loss. A previously unreported sensitive positive component of the scotopic ERG remained in both eyes. In the control eyes, the positive component gave rise to a sharp peak approximately 120 msec after stimulus onset, but in the experimental eyes, because of the absence of the more delayed sensitive negative potential, it was sustained, lasting as long as 700 msec. Scotopic a- and b-waves and oscillatory potentials in the experimental eyes were not consistently different from control eyes. Ganglion cell and optic nerve loss in the experimental eyes was substantial, and there was little other obvious retinal damage. CONCLUSIONS: A sensitive negative component is reduced or absent from the dark-adapted ERGs of macaque monkeys with severe visual field defects and substantial retinal ganglion cell loss as a consequence of long-standing ocular hypertension.

Animals

Behavioral studies of local stereopsis and disparity vergence in monkeys.

Investigations on macaque monkeys have provided much of our knowledge of the neural mechanisms of binocular vision, but there is little psychophysical data on the accuracy of vergence responses or the precision of stereoscopic depth perception in these primates. We have conducted comparative behavioral studies of binocular disparity processing in rhesus monkeys and humans via measurements of prism-induced fixation disparities (disparity vergence) and relative depth discrimination for spatially localized stimuli (local stereopsis). The results of these studies demonstrated a remarkable similarity in both the oculomotor and the sensory aspects of binocular vision in the two species when the stimulus dimensions were specified in visual angles, which were independent of interocular separation. The disparity vergence functions for the two species revealed fusion responses over the same range of prism-induced vergence and comparable vergence errors for stimuli near their fusional limits. Disparity vergence responses were independent of the spatial frequency of the binocular fusion stimulus. Stereothresholds as a function of the spatial frequency of the difference-of-Gaussian stimuli were of the same form, with equivalent stereoacuities, in monkey and human observers. The presence of substantial vergence errors had only a small effect on the precision of stereoscopic depth perception. We conclude that, after compensation for the differences in the lateral separation of their eyes, the operating characteristics of disparity vergence and stereoscopic vision are virtually identical in rhesus monkeys and humans and, consequently, the performance limits for these visual functions must be determined by anatomical and/or neural constraints that are similar in both species.

Animals

Stereopsis, spatial frequency and retinal eccentricity.

Stereoscopic depth discrimination thresholds increase with retinal eccentricity and distance from the horopter. However, in contrast to spatial resolution, the effects of spatial frequency on stereo-thresholds in the periphery are unknown. For spatial vision, it is generally assumed that the retina is comprised of a series of overlapping spatial filter mechanisms and that there is a commensurate increase in spatial scale as a function of retinal eccentricity. If the same holds true for mechanisms sensitive to stereoscopic depth, then stereo-thresholds for low spatial frequency stereoscopic stimuli may remain relatively invariant across the visual field, while thresholds for relatively high spatial frequency stimuli would increase. To further understand the role of the disparity sensitive mechanisms involved in depth discrimination, increment depth discrimination thresholds for both crossed and uncrossed disparities were measured as a function of eccentricity for retinal locations up to 10.0 deg along the horizontal meridian. We found that stereoscopic depth discrimination thresholds, as a function of distance from the horopter, increased in an exponential manner irrespective of spatial frequency. Stereo-thresholds also increased as a function of retinal eccentricity, however, the rate of increase depended on the spatial frequency composition of the stimuli. Best stereo-thresholds for stimuli composed of low spatial frequencies remained relatively invariant for retinal eccentricities up to 10.0 deg, while thresholds for the high spatial frequency stimuli increased with eccentricity.

Depth Perception

Effects of optically induced blur on the refractive status of young monkeys.

In each of eight rhesus monkeys, one eye was defocused with a -9 D contact lens beginning before 1 month of age for periods of 2-3 months. At the end of the rearing period, interocular comparisons showed that one subject had developed a relative axial myopia (3.0 D), however, five monkeys had developed a relative axial hyperopia (2.0-3.5 D). After discontinuing the contact-lens rearing procedure, the induced refractive errors diminished over time in all subjects. These results indicate that the defocus threshold for form-deprivation myopia is relatively high and that substantial levels of optical defocus which do not exceed this threshold typically produce axial hyperopia. The recovery data suggests that monkeys have an emmetropization mechanism which is sensitive to optical defocus, but the failure of this mechanism to compensate for the refractive errors simulated during the lens-rearing procedures suggests that this mechanism has a limited operating range.

Animals

Interocular suppression produced by rivalry stimuli: a comparison of normal and abnormal binocular vision.

This study compares interocular suppression in subjects with early strabismus and/or anisometropia with binocular rivalry suppression in subjects with normal binocular vision. A psychophysical test-probe paradigm was used to measure the changes in luminance-increment detection thresholds associated with periods of phenomenal suppression. In subjects with normal binocular vision, rivalry suppression induced by viewing orthogonally oriented grating pairs produced a distinctive wavelength-dependent change in visual sensitivity; specifically, there was a greater reduction in sensitivity for short (e.g., 450 nm) vs. middle or long wavelength stimuli (e.g., 560 nm). In contrast, subjects with abnormal binocular vision, regardless of the type of early abnormal visual experience, showed more reduction in sensitivity for a 560-nm stimulus than for the short-wavelength, 450-nm stimulus. Moreover, the pattern of sensitivity change in subjects with abnormal binocular vision was the same for suppression induced by either rivalry stimuli or stimuli that would normally promote fusion. The results clearly indicate that interocular suppression in subjects with abnormal binocular vision is qualitatively different from normal binocular rivalry. Evidently, the processes that mediate binocular rivalry are very susceptible to environmental influences during early vision development and can be disrupted easily.

Adolescent

Effects of the spatial frequency of test and reference stimuli on stereo-thresholds.

The perceived depth of adjacent regions of stereoscopic stimuli may be influenced, in part, by differences in the spatial frequency composition of adjacent stimuli. Consequently, it would be predicted that, if the test and reference stimuli differ in their spatial frequency composition, depth discrimination thresholds should be asymmetric about the retinal disparity of the reference stimulus. We measured depth discrimination thresholds with test and reference stimuli that differed by up to 2 octaves in their spatial frequency composition. Stereo-thresholds decreased as a function of spatial frequency to about 2-4 c/deg and were then constant. However, in contrast to the predicted effects, our results show that, for the range of spatial frequencies used, differences of up to 2 octaves in spatial frequency, between test and reference stimuli, do not affect depth discrimination thresholds.

Depth Perception

Precision of stereoscopic depth perception from double images.

The increment depth discrimination function was originally described by Ogle [(1953) Journal of the Optical Society of America, 43, 906-913] as a single exponential function. In contrast, recent studies have suggested that a two-component function better describes increment depth discrimination. To determine the relative effects of stereoscopic and non-stereoscopic width cues on the form of the function, we measured increment depth discrimination under conditions where both stereoscopic and dichoptic width cues were available. We found that increment depth discrimination data were well described by two-segment functions if both stereoscopic and dichoptic width cues were available. However, when dichoptic width cues were eliminated, by randomizing the pedestal disparity (crossed or uncrossed disparity) between trials, the increment depth discrimination function was better described by a single exponential function. This result has important implications for models of stereoscopic depth processing because it shows that stereoscopic depth discrimination thresholds progressively increase as a function of distance from the horopter.

Depth Perception

Keeping an eye on the brain: the role of visual experience in monkeys and children.

The quality of visual experience during infancy determines the functional sensitivity and precision of the mature primate visual system. Infant monkeys subjected to monocular form deprivation show a period of critical visual development that, though decreasing in sensitivity, lasts throughout the first 2 years of life. Photopic threshold spectral sensitivity appears to have a briefer critical period, which is essentially complete by 6 months old, whereas scotopic visual functions appear well developed by 3 months old. Binocular visual functions seem to have the longest period of sensitivity to abnormal visual experience because periods of monocular form deprivation initiated during the first 2 years affect visual functions. Viewing the world through prisms, which mimics the condition of strabismus, causes a permanent loss of cortical binocular cells and stereopsis in monkeys. This result explains stereoblindness in children having equivalent clinical histories.

Animals

Colour vision anomalies following experimental glaucoma in monkeys.

Spectral sensitivity defects, associated with chronic elevated intraocular pressure (IOP) produced by Argon laser trabeculoplasty, were studied in monkeys. Increment-threshold spectral sensitivity (ITSS) and threshold versus intensity (TVI) functions were measured using a behavioural model. Elevated IOP resulted in short wavelength (SW) sensitivity losses characteristic of many ocular diseases. The amount of SW sensitivity loss for ITSS functions depended upon the intensity level and chromatic composition of the background field. The optimum condition identifying the greatest SW sensitivity reduction was a yellow background of moderate intensity (100-1000 Td). In the early stages of experimental glaucoma, the cone mechanisms and the rod mechanism typically showed decreased test and field sensitivities. The SW cone pathway has slightly greater threshold elevation (approximately 0.3 log unit) compared to the rod and cone pathways. On the other hand, in the advanced stages of experimental glaucoma, the largest sensitivity losses were in the longer-wavelength, red-green opponent mechanisms, with the rod and SW cone pathways showing smaller losses. The similarities of the colour vision anomalies in this animal model with those of patients with glaucoma, provides support for its use as an experimental model for human glaucoma.

Animals

Modelling sensitivity losses in ocular disorders: colour vision anomalies following intense blue-light exposure in monkeys.

The effects of prolonged exposure to intense, short-wavelength light were studied in monkeys through the measurement of increment-threshold spectral sensitivity (ITSS) and threshold-versus-intensity (TVI) functions using a behavioural method. The long-term effect of intense blue-light exposure was to induce a short-wavelength (SW) sensitivity loss which did not depend on the intensity or chromatic composition of the adapting field. The TVI curves for short wavelength stimuli revealed an increase in test threshold without changes in field sensitivity. Since this SW sensitivity loss may generalize to characteristic colour vision defects found in many outer retinal diseases, models of acquired alterations of colour vision mechanisms are considered. These models describe probable changes in ITSS functions and TVI curves in diseases affecting the inner or outer retina as well as changes in dark adaptation.

Animals

Mechanisms mediating visual detection in static perimetry.

PURPOSE: The usual stimuli in static perimetry are white-light luminance increments. However, the specific visual detection mechanisms involved in perimetry are unknown because all classes of neural mechanisms are sensitive to spectrally broadband stimuli. The objective of this study was to determine the relative sensitivities of nonopponent and opponent detecting mechanisms under standard perimetry test conditions. METHODS: Using trained rhesus monkey subjects, the relative sensitivities of the vision mechanisms for the detection of perimetry test stimuli were determined through psychophysical measurements of spectral sensitivity at each of the test field locations of the C24-2 threshold program on the Humphrey Field Analyzer (Allergan Humphrey, San Leandro, CA). The spectral sensitivity functions were analyzed by a three-channel model that incorporated independent short-wavelength-sensitive, nonopponent (luminance), and opponent (chromatic) spectral sensitivity mechanisms. RESULTS: The visual detection mechanisms for perimetry thresholds varied as a function of the size and wavelength of the test field. With the perimeter's standard stimulus (Goldmann Size III) and bowl illumination (31.5 asb), the presence of a short-wavelength-sensitive mechanism was clearly evident at all field locations, but its relative sensitivity systematically declined with eccentricity. Under these conditions, the sensitivities of the opponent and nonopponent mechanisms were approximately equal at most field locations. With a larger stimulus (Goldmann Size V), however, the contribution of the opponent spectral sensitivity mechanism was more apparent over most of the central field and the alterations of sensitivity with eccentricity were less pronounced. In contrast, a small test field (Goldmann Size II) appeared to bias detection toward nonopponent mechanisms. CONCLUSION: The results of these investigations indicate that detection thresholds during perimetry can be effectively biased toward different photopic, visual processing channels through the appropriate selection of size and wavelength of the test stimulus.

Animals