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Biomedical subjects

R S Harwerth

Publications and source records attributed to R S Harwerth.

At least 55 records · Page 3Linked to original sources

Binocular beat VEPs: losses of cortical binocularity in monkeys reared with abnormal visual experience.

Binocular beat VEPs were recorded from anesthetized macaque monkeys with diverse visual rearing histories, including surgically induced esotropia, optical prism dissociation, optical anisometropia, monocular form deprivation (MD), and normal rearing. Dichoptic visual stimulation was produced by temporally modulating the luminances of uniform fields presented to each eye. Five pairs of temporal frequencies were used, all of which had interocular differences of 2 Hz. While normally reared animals exhibited robust binocular beat responses strongly tuned to temporal frequency, the responses from monkeys with abnormal rearing experiences showed losses in beat signal-to-noise ratios that correlated with the age of onset or duration of the abnormal visual experience. Surgical esotropia induced early in life (2 months of age) produced a virtually complete loss of the binocular beat response; the cortical losses were less severe as the age of surgery rose to 10 months. Monkeys reared with either anisometropia or optical dissociation also manifested substantial reductions in evoked beat nonlinearity. MD monkeys sutured relatively late in development (8 and 25 months) showed mild reductions. The correspondence of these results to earlier psychophysical data obtained from these animals, and the similarity of these results to previous findings with binocularly normal and abnormal humans, supports the use of the binocular beat as an objective, noninvasive index of binocular neural integrity.

Amblyopia↗

Functional effects of bilateral form deprivation in monkeys.

Psychophysical methods were used to study the effects of binocular form deprivation, initiated at 1 month of age, on the visual sensitivities of young monkeys. All the monkeys reared with bilateral form deprivation for 7 weeks or longer had reduced spatial contrast sensitivity for both eyes. Although the contrast sensitivity deficits of the bilaterally form-deprived monkeys generally were larger for one eye than the other, the magnitudes of the deficits were small compared with those produced by similar periods of unilateral form deprivation. For other monocular vision functions investigated, temporal contrast sensitivity and increment-threshold spectral sensitivity, the data for the bilaterally form-deprived animals showed only minor variations from those of the control monkeys. However, none of the bilaterally form-deprived monkeys had binocular vision on either measures of binocular summation or stereodetection, even if the animal had normal monocular vision functions. Therefore, these results show that monocular sensory deficits caused by abnormal early visual experience as a result of bilateral form deprivation are much less severe than those caused by unilateral form deprivation. The differences in the severity of visual deficits may be attributed to the consequences of anomalous binocular competition associated with unilateral form deprivation that was minimized during bilateral form deprivation. Thus, these results illustrate that anomalous binocular competition is more detrimental to the developing visual system of infants than direct deprivation per se.

Amblyopia↗

Bilateral form deprivation in monkeys. Electrophysiologic and anatomic consequences.

The response characteristics of neurons in the striate cortex are described for rhesus monkeys that underwent bilateral form deprivation by surgical closure of the eyelids starting within the first month of life and lasting for 2, 6, 7, 13, or 16 weeks. The monkeys had been tested for visual deficits resulting from these experimental deprivations. Single-unit recordings from the striate cortices of these animals showed a single significant abnormality; the absence of excitatory binocular input. Whereas, 76% of the neurons in the foveal striate cortex of the normal animals were binocular, fewer than 20% of the neurons in the experimental monkeys were binocular. However, each eye was well represented by monocular cells. As demonstrated in oblique microelectrode penetrations, the cortical eye-dominance zones for each eye appeared to be of equal width with sharp transitions at the monocular boundaries. The sizes of the cells of the lateral geniculate nuclei were smaller (-15%) than those in controls. Binocular form deprivation early in life has its most obvious effect on the physiology and function of cortical binocular neurons and secondarily on the size of neurons of the lateral geniculate nucleus.

Animals↗

Behavioral studies of the sensitive periods of development of visual functions in monkeys.

The age-dependent effects of monocular form deprivation on psychophysically determined visual functions were investigated in rhesus monkeys. Monocular form deprivation was initiated at various ages from 1 to 25 months and maintained for 18 months. The effects of form deprivation varied across the visual functions evaluated. Absolute scotopic sensitivity was depressed by form deprivation initiated only at 1 or 2 months of age. Photopic, increment-threshold spectral sensitivity functions showed alterations in sensitivity levels for monkeys treated at 5 months of age or earlier, with no effect thereafter. Monocular form deprivation at 1 to 5 months of age resulted in profound deficits in spatial modulation sensitivity. The effects on spatial vision decreased systematically as the age of onset was delayed from age 6 to 18 months. Finally, binocular summation measures revealed an absence of binocular vision even for the monkey form-deprived at 25 months of age, i.e. the experimental treatment series failed to define the upper limit of the age-range for the effects of monocular form deprivation on binocular summation mechanisms. Comparisons of the age-dependent effects of monocular form deprivation across the various functions demonstrated that the sensitive period, i.e. the period of life during which a visual function may be altered by monocular form deprivation, was different for each of the psychophysical measures of visual function.

Animals↗

Spectral sensitivity and adaptation characteristics of cone mechanisms under white-light adaptation.

Increment-threshold spectral-sensitivity (ITSS) functions and threshold-versus-intensity (tvi) curves were measured under white-light adaptation in rhesus monkeys. The tvi curves showed shape and test wavelength invariance, implying that three cone mechanisms were mediating detection. In general, the results were in agreement with the differential adaptation hypothesis proposed by Stiles that predicted spectral shape invariance of the cone mechanisms but overall changes in the shape of the spectral-sensitivity function with increases in the intensity of the adapting field. The principal changes occurring in the ITSS function as the level of adaptation increased involved a smaller loss in sensitivity of the short-wavelength and the long-wavelength peaks compared with the corresponding loss in sensitivity of the middle-wavelength peak. A three-channel model with an opponent L-M mechanism and a nonopponent L-M mechanism (both with S-cone input) and an independent S-cone mechanism described the ITSS data as well as other increment-threshold and suprathreshold data. The model values for the ITSS functions, along with parameters derived from the transformation of these data to cone-contrast coordinates, permitted the factoring out of first-site adaptation, second-site adaptation, and the relative strengths of contribution of the L and M cones within the opponent and nonopponent L-M channels.

Adaptation, Ocular↗

Visual fields of monocularly deprived macaque monkeys.

The effects of postnatal monocular deprivation have been studied in macaque monkeys using behavioral perimetry field testing. The types of deprivation were: (1) early eyelid suture at 22-26 days after birth and then reverse suture at 10-13 months postnatally, (2) late eyelid suture beginning at 3 or 5 months postnatally and continued for 18 months, and (3) long-term occlusion by contact lenses. Response levels were normal for group 1 monkeys with some reduction in visual field extent. A reduced response level but no change in visual field extent was observed for the deprived eyes of group 2 monkeys. One monkey from group 3 that wore an occluder lens from birth to 19 months postnatally had no responses in any part of the visual field. Two other monkeys of group 3, whose occlusion started at 9 or 12 days of age and lasted for 2 years, had no responses to stimuli presented to the previously occluded eyes in their nasal visual fields and had reduced levels of response to stimuli presented in their temporal fields. The results indicate that the effects of monocular deprivation on macaque monkeys are affected by the start, length and type of deprivation. Some of these results are also consistent with a model of binocular competition in which the magnitude of the competition declines along a nasal-to-temporal gradient of visual field eccentricity. However, a mechanism that is independent of binocular competition is needed to account for the loss of responses to stimuli presented in the monocular visual segment.

Animals↗

The effects of reverse monocular deprivation in monkeys. I. Psychophysical experiments.

Monkeys had one eye closed at about 30 days of age for 14, 30, 60, or 90 days, then opened, and the fellow eye closed for another 120 days. The animals then had at least 10 months of binocular visual experience before behavioral training and testing were begun. All subjects were used in a series of psychophysical investigations during the next two years. The results of the behavioral studies indicated that the initially deprived eyes (IDE) of the two monkeys that were subjected to initial deprivation periods of 14 or 30 days recovered normal or near-normal spatial contrast sensitivity. In contrast, the two animals which underwent longer periods of initial deprivation showed incomplete recovery, especially for high spatial frequency stimuli. All of the monkeys exhibited a reduction in spatial contrast sensitivity for their reverse deprived eyes (RDE); the earlier the onset of the reverse-deprivation procedures (i.e., the shorter the initial period of deprivation), the greater the deficit in the RDE's spatial contrast sensitivity. Measurements of temporal contrast sensitivity showed that all of the subjects' IDEs had normal or near-normal sensitivity levels. However, the reverse-deprivation procedures initiated at 90 days of age or earlier produced a frequency-dependent reduction in the RDE's temporal modulation sensitivity. The measures of increment-threshold spectral sensitivity revealed that only the RDE of the monkey that had the shortest initial deprivation period had an abnormal spectral sensitivity function. The results demonstrate that many of the severe behavioral deficits produced by early monocular form deprivation can be recovered via reverse-deprivation procedures. However, depending upon the length of the initial deprivation period and the age at which the reversal procedure is initiated, the second deprivation period can also adversely affect the functional capacity of the RDE.

Animals↗

The effects of reverse monocular deprivation in monkeys. II. Electrophysiological and anatomical studies.

Monkeys had one eye closed at about 30 days of age for 14, 30, 60, or 90 days, then opened, and the fellow eye closed for another 120 days. The animals then had at least 10 months of binocular visual experience before extensive behavioral training and testing were carried out. In terminal experiments concluded more than 18 months later, microelectrode investigations of the striate cortex demonstrated that there was almost a complete absence of binocular neurons in all animals. The initially deprived eyes (IDEs) dominated the majority of cortical neurons, even when soma size measurements of lateral geniculate neurons indicated that the LGN cells driven by the IDE had not regained their normal size. The monkeys which had significant interocular differences in spatial vision also exhibited abnormalities in the distribution of the metabolic enzyme, cytochrome oxidase (CO), within the striate cortex. These results demonstrate that many of the severe alterations in cortical physiology and eye dominance produced by early monocular form deprivation can be reversed, with recovery of normal cortical function, via the reverse-deprivation procedure.

Animals↗

Contribution of the retinal ON channels to scotopic and photopic spectral sensitivity.

Visual information encoded by the middle-wavelength-sensitive (MWS) and long-wavelength-sensitive (LWS) cones in the primate retina are processed by both depolarizing (ON) and hyperpolarizing (OFF) bipolar cells. In contrast, signals from the short-wavelength-sensitive (SWS) cones and dark-adapted rod photoreceptors are thought to be carried almost exclusively by ON bipolar cells (Gouras & Evers, 1985). Consequently, it would be expected that functional inactivation of the retinal ON channels at the bipolar cell level would produce selective deficits in visual functions mediated by rods and SWS cones. We have examined this hypothesis by injecting rhesus monkeys with 2-amino-4-phosphonobutyric acid (APB), a pharmacological agent that reduces the responsiveness of retinal ON neurons, and psychophysically measuring the changes in spectral sensitivities. Under adaptation conditions that isolated rod function, APB caused, as expected, a substantial loss in rod-mediated spectral sensitivity. However, under photopic conditions, cone-mediated spectral sensitivity, including that associated with the SWS cones, was relatively unaffected. These results demonstrate distinct organizational differences between the rod and cone systems; specifically, they indicate that the rod system is more dependent upon retinal ON channels than the cone system. Our failure to find a selective visual deficit related to SWS cone function under photopic viewing conditions suggests that the OFF system can mediate stimulus detection throughout the visible spectrum and that the ability of the OFF system to process signals from the SWS cones has been underestimated.

Aminobutyrates↗

Observations on the effects of form deprivation on the refractive status of the monkey.

The consistency of the refractive error alterations produced by monocular form deprivation in developing monkeys and the influence of the duration and the age at the onset of deprivation on the magnitude of these alterations was investigated. Refractive error and axial length measurements are presented for a group of monkeys which had one eye sutured closed for a period exceeding 18 months beginning at various ages ranging from 26 days to 25 months. In addition, we pooled and reanalyzed refractive error and axial length data for monocularly form-deprived monkeys from previous studies. When the alterations in the deprived eye's refractive status are specified with respect to the fellow nondeprived eye, the results are, with a few noteworthy exceptions, consistent between laboratories and individual animals. In most cases, early monocular form deprivation causes the treated eye to develop a longer axial length and to manifest a more myopic/less hyperopic refractive error than the fellow nontreated eye. The magnitude of this deprivation-induced alteration is generally dependent on the duration and the age at the onset of form deprivation. The earlier the deprivation is initiated and the longer it is maintained, the greater the degree of the relative myopia produced in the deprived eye.

Animals↗

Multiple sensitive periods in the development of the primate visual system.

Early in life, abnormal visual experience may disrupt the developmental processes required for the maturation and maintenance of normal visual function. The effects of retinal image deprivation (monocular form deprivation) on four psychophysical functions were investigated in rhesus monkeys to determine if the sensitive period is of the same duration for all types of visual information processing. The basic spectral sensitivity functions of rods and cones have relatively short sensitive periods of development (3 and 6 months) when compared to more complex functions such as monocular spatial vision or resolution (25 months) and binocular vision (greater than 25 months). Therefore, there are multiple, partially overlapping sensitive periods of development and the sensitive period for each specific visual function is probably different.

Age Factors↗

A comparison of the spectral sensitivities of monkeys with anisometropic and stimulus deprivation amblyopia.

Psychophysical procedures were used to determine increment-threshold spectral sensitivity functions for monkeys with either stimulus deprivation amblyopia produced by monocular lid suture or anisometropic amblyopia produced by optical defocus. The spectral sensitivity functions obtained from all of the non-treated control eyes had 3 sensitivity maxima at approximately 445, 520 and 610 nm, and were typical of functions for humans and monkeys with normal trichromatic vision. Relative to their paired control eyes, the amblyopic eyes of all of the lid-sutured monkeys demonstrated reductions in absolute sensitivity. In addition, the amblyopic eyes of the monkeys form-deprived at 1 month of age exhibited alterations in the shapes of their spectral sensitivity functions. The pattern of spectral sensitivity deficits observed in the monkeys form-deprived at 1 month of age varied with the duration of deprivation and indicated that the spectral characteristics of the neural mechanisms mediating stimulus detection in these lid-sutured monkeys' amblyopic and control eyes were substantially different. In contrast, none of the anisometropic amblyopes demonstrated any alterations in the shapes of their spectral sensitivity functions and only one anisometropic subject exhibited a reduction in sensitivity. A comparison of the spectral sensitivity deficits observed in our lid-sutured and anisometropic monkeys reveals that when lid suture and optical defocus are initiated early in life for equivalent periods of time, lid suture produces abnormalities which are both qualitatively and quantitatively different from the abnormalities produced by optical defocus. Therefore, in addition to factors such as the age of onset and the duration of deprivation, it is concluded that the degree of image degradation is important in determining which visual functions are affected and to what extent they are affected.

Amblyopia↗

Effects of enucleation of the fixating eye on strabismic amblyopia in monkeys.

The effects of enucleation of the fixating eye on the visual function of the deviating eye were studied in two rhesus monkeys with strabismic amblyopia. An esotropia was surgically induced when the monkeys were approximately 1 mo of age, and the fixating eyes were then enucleated at age 3 yr 11 mo. Four measures of visual function (photopic increment-threshold spectral sensitivity, scotopic spectral sensitivity, spatial modulation sensitivity, and temporal modulation sensitivity) were determined for both eyes prior to enucleation and for the deviating eyes over an 11-month period following the surgical removal of the fixating eye. Both monkeys showed some recovery of contrast sensitivity of their deviating eyes. The extrapolated cut-off values for their spatial modulation sensitivity functions increased from .27 to 2.8 c/deg for one animal and from .28 to 6.3 c/deg for the other. The extrapolated cut-off frequencies for the temporal modulation sensitivity functions of both animals showed an increase of 20-25 Hz compared to the pre-enucleation values. The spectral sensitivity functions of one monkey recovered to near normal values following enucleation, while both the photopic and scotopic functions of the other animal remained at pre-enucleation levels. Overall, the results of the experiments indicate that the removal of the fixating eyes of monkeys with strabismic amblyopia can result in significant improvements in the functional capacity of their deviating eyes.

Amblyopia↗

Binocular summation in man and monkey.

Binocular summation, using spatial and temporal modulation sensitivity measurements, has been investigated for human and rhesus monkey observers. In experiments where the refractive errors of both eyes were optimally corrected, the binocular summation functions for both species were similar in magnitude and form, and showed higher summation ratios for temporally modulated stimuli than for spatially modulated stimuli. Monocular retinal image defocus produced a reduction in binocular summation for spatial gratings with the amount of reduction dependent on both the amount of relative defocus and the spatial frequency of the stimulus grating. In contrast, monocular defocus did not effect the magnitude of binocular summation for spatial gratings with the amount for any of the conditions investigated. Over-all, the results of these investigations indicate that binocular summation measures of binocular function may have some advantages over other tests of binocular function that could be utilized in the clinical examination of patients.

Adult↗

Rhesus monkey as a model for normal vision of humans.

Data for three fundamental psychophysical functions (spatial modulation sensitivity, temporal modulation sensitivity, and increment-threshold spectral sensitivity) were compared for groups of 12 rhesus monkeys and 12 human subjects. It was found that there are important, nontrivial differences between the data for monkeys and humans, but that many of the differences could be accounted for by structural or passive differences in the visual systems. Therefore, it was concluded that the neural processing of information along the visual pathways of the two species is generally similar and that the monkey is an excellent model of the human visual system.

Animals↗

The relationship between binocular rivalry and strabismic suppression.

Increment-threshold spectral sensitivity functions were determined for normal observers during binocular rivalry and for esotropic observers during strabismic suppression and under viewing conditions that normally induce binocular rivalry. Depending on the spatial and temporal properties of the test stimulus, the normal observers exhibited a wavelength-specific loss in sensitivity during the suppression phase of rivalry, which suggests that binocular rivalry differentially attenuates the sensitivity of the chromatic mechanisms relative to the luminance mechanisms. In contrast, regardless of the test stimulus dimensions, the esotropic observers did not manifest a wavelength-specific loss in sensitivity either during strabismic suppression or under conditions that normally induce binocular rivalry. The different patterns of suppression shown by the normal and esotropic subjects suggest that strabismic observers do not demonstrate normal binocular rivalry, and that strabismic suppression and normal binocular rivalry suppression are mediated by different neural mechanisms.

Adult↗

Spatial contrast sensitivity deficits in monkeys produced by optically induced anisometropia.

An anisometropia was simulated in infant rhesus monkeys by securing a high-powered minus lens (-10 D) in front of one eye. The anisometropia rearing procedure was initiated at 30 days of age and was continued for durations of 30, 60, or 90 days. Behavioral measurements of spatial contrast sensitivity obtained when the animals were 9 months of age indicated that the monkeys treated for 30 days had equal or nearly equal contrast sensitivities and cut-off spatial frequencies in the two eyes. The 30-day monkeys also demonstrated normal binocular summation for threshold stimuli. In contrast, the monkeys treated for either 60 or 90 days showed a significant reduction in contrast sensitivity in the defocused eyes for spatial frequencies greater than 1.0 cycles/deg and failed to show an improvement in contrast sensitivity under binocular viewing conditions. The cut-off spatial frequencies obtained at moderate luminance levels for the defocused eyes of the 60- and 90-day monkeys were slightly more than 1.0 octave lower than the cut-offs for the nondeprived eyes and, like humans with anisometropic amblyopia, the deficits in the spatial resolving capacity of the defocused eyes were observed over a large range of background luminances. The results indicate that the lens-reared monkey is a promising model for anisometropic amblyopia in humans.

Animals↗

Behavioral measurements of accommodative amplitude in rhesus monkeys.

The extent of voluntary accommodation was investigated behaviorally in two young rhesus monkeys and an adult human using a modified minus-lens technique. Specifically, contrast sensitivity for a high spatial frequency grating was determined as a function of spectacle lens power. Accommodative amplitudes derived from contrast sensitivity vs lens power functions indicate that young monkeys have at least 17 to 18 D of voluntary accommodation and that the accommodative amplitudes of monkeys are larger than those of equivalent-aged humans.

Accommodation, Ocular↗