Residual Binocular Interactions in the Striate Cortex of Monkeys Reared With Abnormal Binocular Vision
Earl L. Smith III1,
Yuzo M. Chino1,
Jinren Ni1,
Han Cheng1,
M.L.J. Crawford2, and
Ronald S. Harwerth1
1 College of Optometry, University of Houston, Houston, 77204-6052; and 2 Department of Ophthalmology and Visual Science, University of Texas, The Medical School, Houston, Texas 77030
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ABSTRACT |
Smith, Earl L., III, Yuzo M. Chino, Jinren Ni, Han Cheng, M.L.J. Crawford, and Ronald S. Harwerth. Residual binocular interactions in the striate cortex of monkeys reared with abnormal binocular vision. J. Neurophysiol. 78: 1353-1362, 1997. 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.
 |
INTRODUCTION |
Although many of the neural connections that support binocular single vision in the primate striate cortex (V1) are established (Horton and Hocking 1996
; LeVay et al. 1980
) and functional at or shortly after birth (Chino et al. 1997
; Wiesel and Hubel 1977), the maintenance and refinement of these innate connections are highly dependent on normal binocular visual experience. It is well known that early in life discordant binocular vision can have devastating effects on cortical binocularity (Movshon and Kiorpes 1990
). For example, misalignment of the visual axes of infant monkeys (i.e., strabismus) exaggerates the normal segregation of ocular dominance columns and decreases the proportion of cortical neurons that can be excited through both eyes (Baker et al. 1974
; Crawford and von Noorden 1979
, 1980
). And depriving one eye of form vision early in life can produce dramatic changes in the balance of inputs from the two eyes to individual neurons (Baker et al. 1974
; Blakemore et al. 1978
; Crawford et al. 1975
; LeVay et al. 1980
).
However, these previous investigations of the effects of abnormal visual experience on cortical binocularity in primates have relied primarily, if not exclusively, on measures of ocular dominance. Specifically, monocular stimuli were presented alternately to each eye to assess the relative effectiveness of the left and right eyes in exciting a neuron. Although measures of ocular dominance have provided valuable information on the effects of abnormal visual experience, ocular dominance measures alone cannot explain many aspects of the binocular vision in individuals who experienced abnormal binocular vision early in life. For instance, ocular dominance measures would suggest that there should be a virtual absence of binocular interactions in individuals with strabismus. However, both clinical and psychophysical observations have demonstrated that strabismic subjects show robust binocular interactions. In particular, binocular suppression is common under ordinary viewing conditions in strabismus (von Noorden 1990
), and in dichoptic masking experiments strabismics show antagonistic binocular interactions that are as finely tuned to orientation and spatial frequency as those in normal observers (Levi et al. 1979
). In addition to being insensitive to antagonistic binocular interactions, ocular dominance measures are also insensitive to weak or subthreshold excitatory inputs and thus can overestimate the degree of neural alteration (Chino et al. 1994
; Freeman and Ohzawa 1988
; Freeman and Robson 1982
).
The purpose of this study was to determine the nature of the residual binocular interactions in monkey models for the two most common causes of binocular visual dysfunction in young children, specifically in monkeys reared with either anisometropia or strabismus. Some of these results have been briefly presented elsewhere (Crawford et al. 1996a
; Ni et al. 1990
; Smith et al. 1992
).
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METHODS |
Subjects
All experimental and animal care procedures were in compliance with the policies of the American Physiological Society and the National Institutes of Health Guide for the Care and Use of Laboratory Animals.
Binocular interactions in individual V1 neurons were investigated in four macaque monkeys (Macaca mulatta) reared with an optically induced anisometropia and three macaques reared with an optically induced strabismus. Within the first 30 days of life, each animal was fitted with a lightweight helmet that secured either spectacle lenses or ophthalmic prisms in front of the two eyes (see Table 1). The optical effects of an anisometropia were simulated by placing a
10-D lens in front of the treated eye and a zero-powered lens in front of the fellow, control eye (Smith et al. 1985
). This rearing strategy chronically defocused the retinal image in the treated eye by ~10 D at all fixation distances. The diplopia and confusion associated with a concomitant strabismus were simulated by placing 10-
and 17-
prisms oriented base-in in front of the left and right eyes, respectively (Crawford and von Noorden 1980
). The total prismatic deviation greatly exceeded the fusional vergence ranges of normal monkeys (Boltz and Harwerth 1979
) and thus precluded binocular fusion of most ordinary objects. During the rearing period, the prism-reared monkeys exhibited alternating fixation patterns; no obvious left or right eye preferences were noted.
The experimental monkeys wore the lenses/prisms continuously for periods ranging between 15 and 90 days (Table 1). At the end of the treatment period, the helmets were removed and the monkeys were allowed unrestricted vision in a normally lighted environment. After 1 yr of age, the animals were trained to perform operant behavioral tasks and psychophysical procedures were employed to assess the monkeys' spatial contrast sensitivity and their binocular vision. Video recordings of the corneal light reflexes indicated that all of the experimental monkeys were orthotropic at the time of the behavioral experiments.
All four lens-reared monkeys exhibited the high-spatial-frequency loss in contrast sensitivity (Fig. 1) that is characteristic of humans with anisometropic amblyopia (Levi 1991
). In comparison, the prism-reared monkeys generally showed milder interocular differences in contrast sensitivity. Permanent behavioral alterations in binocular vision were also documented in the experimental subjects (Table 1). None of the prism-reared animals were able to discriminate targets embedded in random-dot stereograms, nor did any of the strabismics show evidence of binocular summation (Crawford et al. 1983
, 1996b
; Ridder 1989
). One of the lens-reared subjects, mky 215, demonstrated normal binocular summation for spatial frequencies <8 cycles/deg but an absence of summation for higher spatial frequencies. Binocular summation was absent at all spatial frequencies for the three other lens-reared monkeys (Smith et al. 1985
, 1992
).

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| FIG. 1.
A: spatial contrast sensitivity (mean ± SE) plotted as a function of spatial frequency for the right ( ) and left ( ) eyes of representative lens-reared (mky 214, left) and prism-reared (mky 197, right) monkeys. B: interocular differences in contrast sensitivity, expressed as the log of the ratio of contrast sensitivities for the control vs. the treated (or right) eyes, plotted as a function of spatial frequency for the 4 lens-reared monkeys (left: , mky 209; , mky 213; , mky 214; , mky 215) and the 3 prism-reared monkeys (right: , mky 190; , mky 193; , mky 197). Points plotted above the dashed 0 line: treated or right eyes showed a relative deficit in contrast sensitivity.
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Control data were obtained from the 11 normally reared macaque monkeys that were described in the preceding papers (Smith et al. 1997a
,b
).
Surgical preparation and recording procedures
The surgical preparation, apparatus, general recording procedures, and specific experimental paradigms were identical to those described in detail in the preceding papers (Smith et al. 1997a
,b
). In brief, the responses from individual V1 neurons were recorded with the use of extracellular microelectrodes while the animals were anesthetized and paralyzed. For each isolated neuron, ocular dominance was determined with the use of hand-held stimuli (Hubel and Wiesel 1962
) and the residual binocular interactions were investigated with the use of a dichoptic disparity tuning paradigm (Freeman and Robson 1982
; Ohzawa and Freeman 1986a
,b
). This paradigm requires a knowledge of key monocular response properties. Therefore each cell's basic monocular response properties were first determined by measuring orientation response functions and spatial frequency tuning functions independently for each eye with the use of drifting sine wave gratings. Next the sensitivity of each cell for retinal disparity was determined by measuring the cell's responses as a function of the relative interocular spatial phase of dichoptic grating pairs. In these experiments, drifting grating stimuli of the optimal spatial frequency were presented at the optimal orientation and direction of drift. Typically, responses were collected for 16 dichoptic grating pairs that had different relative interocular spatial phases. The range of spatial phase differences varied from 0 to 360° in 22.5° steps. In addition, monocular stimuli for each eye and one blank control (0 contrast) were included in the parameter file to provide important reference data. In all of the above experiments, the stimulus temporal frequency was typically 3.12 Hz and the contrast was held constant, usually at 0.3.
For descriptive and analytic purposes, the disparity tuning functions were fit with a single cycle of a sine wave (Ohzawa and Freeman 1986a
). The sine wave's amplitude was used to calculate the degree of binocular interaction [binocular interaction index (BII) = amplitude of the fitted sine wave/average binocular response amplitude]. A signal-to-noise ratio (amplitude of the fitted sine wave/residual root-mean-square error of the fit) was calculated to determine the adequacy of the fitted sine wave in describing a cell's phase tuning characteristics.
For some neurons that were selected because they had very stable, well-isolated action potentials and moderate or high firing rates, binocular contrast summation was investigated by measuring contrast response functions for optimal dichoptic grating pairs that had left- to right-eye interocular contrast ratios that varied from 0.1 to 10. The goal was to determine the left- and right-eye contrast levels required to produce a criterion response amplitude at each interocular contrast ratio (Smith et al. 1997a
).
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RESULTS |
All of the neurons were encountered in the operculum of V1 and had receptive fields between 1.5 and 4° of the fovea. A total of 155 and 94 neurons were investigated in the lens- and prism-reared monkeys, respectively, of which 51% and 95% were recorded in the hemisphere contralateral to the amblyopic eyes.
Ocular dominance
The ocular dominance distributions for neurons in the treated monkeys differed from those of normal animals in several respects (Fig. 2). For both simple and complex cell populations, there was a decrease in the proportion of neurons that were driven equally, or nearly equally, by stimuli presented to either eye, and an increase in the proportion that could only be excited by stimuli presented to one eye. In general, the ocular dominance alterations were qualitatively similar for the lens- and prism-reared monkeys, with the prism-reared animals showing slightly greater numbers of monocular neurons. Overall, the ocular dominance changes compare favorably with those reported previously for monkeys with blur-induced amblyopia (Movshon et al. 1987
) or optically induced strabismus (Crawford and von Noorden 1980
).

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| FIG. 2.
Ocular dominance distributions of simple (left) and complex (right) cells based on the 7-category scheme of Hubel and Wiesel (1962) . For the normal monkeys, categories 1 and 7 represent monocular neurons that were driven exclusively by the contra- and ipsilateral eyes, respectively. Categories 2-6 represent neurons excited through both eyes. The relative influence of the contralateral eye decreases and that of the ipsilateral eye increases from categories 2 to 6, with category 4 consisting of neurons that were driven equally by each eye. For the lens- and prism-reared monkeys, the right/amblyopic eyes were designated as the contralateral eyes.
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Sensitivity to relative interocular spatial phase
For dichoptic gratings that incorporated the optimal monocular stimulus parameters, the residual binocular interactions observed in the treated monkeys were qualitatively similar to those in normal animals (Fig. 3). As in normal animals, the binocular responses of many cells in the lens- and prism-reared monkeys, particularly simple cells (Fig. 3, left), varied systematically as a function of the relative interocular spatial phase of the dichoptic stimuli. And in both normal and treated monkeys, the fitted sine functions provided a good description of the binocular phase tuning data. As reflected by the relative position of the dichoptic data with respect to the monocular response amplitudes, the nature of binocular interaction varied from cell to cell. Clear indications of both cooperative and antagonistic binocular interactions were observed in the treated monkeys, often within the same cell. For example, all of the simple units shown in Fig. 3 exhibited both binocular facilitation (maximum binocular response greater than the better monocular response) and binocular suppression (minimum binocular response less than the better monocular response). In all subjects, all simple cells that were excited by monocular stimuli presented to each eye alone demonstrated binocular interactions during dichoptic stimulation. However, robust binocular interactions, both binocular facilitation and binocular suppression, were also observed in cells that were only excited through one eye during monocular testing (Fig. 3, A and C).

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| FIG. 3.
Binocular phase tuning functions for representative simple (left) and complex (right) cells from normal (top), prism-reared (middle), and lens-reared (bottom) monkeys. Filled circles: response amplitude (1st Fourier harmonic for simple cells and average firing rate for complex cells) plotted as a function of the relative interocular spatial phase difference between the optimal dichoptic gratings. Base-up and base-down triangles on right ordinate: left- and right-eye monocular response amplitudes, respectively. Open diamonds on right ordinate: level of spontaneous activity. Binocular interaction index (BII) and signal-to-noise ratios are given for each cell in the figure. BII values represent the amplitude of the sine wave fitted to a cell's phase tuning function divided by the average binocular response. Signal-to-noise ratio values equal the amplitude of the fitted sine wave divided by the residual root-mean-square error of the fit. Ratios comparing the maximum and minimum binocular response amplitudes to the better monocular response were also calculated from the fitted sinusoids.
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The degree of disparity tuning in all three subject groups was generally lower in complex cells (Fig. 3, right) than in simple cells. But it is important to note that in both the normal and treated animals, clear binocular interactions were apparent in complex cells that were not sensitive to binocular disparities (i.e., non-phase-specific complex cells). For example, the phase tuning function for the complex cell from the prism-reared monkey (Fig. 3D) is relatively flat; however, this cell exhibited strong binocular suppression. Similar response patterns were observed in complex cells from normal (Smith et al. 1997b
) and lens-reared monkeys. As shown by the complex unit from the lens-reared monkey (Fig. 3F), cooperative binocular interactions were also observed in non-phase-specific complex cells, i.e., the binocular response amplitudes were relatively independent of phase disparity, but the binocular responses exceeded the larger monocular response for all the dichoptic stimuli.
Although their phase tuning functions were qualitatively normal, the treated monkeys showed obvious quantitative reductions in the degree of disparity tuning. In Fig. 4, BII values are plotted as a function of the ocular dominance index for individual cells. In comparison with normal monkeys, both the lens- and prism-reared monkeys showed a lower proportion of simple and complex cells with high BII values (t-test, P < 0.001) and for the complex cell population the decrease in BII was greater in the lens- versus the prism-reared monkeys (t-test, P < 0.003). The overall decrease in disparity selectivity reflects an increase in the proportion of truly monocular neurons, i.e., neurons that showed no signs of binocular interaction and that only responded to monocular stimuli presented to one eye (ocular dominance index = 0 or 1.0). In both the lens- and prism-reared monkeys, approximately twice the normal percentages of neurons were truly monocular (15 and 17%, respectively, vs. 7% for normals). However, the treatment-induced decrease in disparity sensitivity was not simply caused by a relative reduction in the excitatory inputs from one eye. Regardless of ocular dominance, few complex cells, particularly in the lens-reared monkeys, showed even moderate degrees of disparity tuning.

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| FIG. 4.
BII values for individual simple (left) and complex (right) cells plotted as a function of the ocular dominance index for normal (top), lens-reared (middle), and prism-reared (bottom) monkeys. For a given cell, the ocular dominance index values were calculate by dividing the monocular response amplitude for the left eye obtained during the phase tuning experiment by the sum of the left- and right-eye monocular responses. Ocular dominance index values of 0 and 1.0: cells excited exclusively by the right (amblyopic) and left eyes, respectively.
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Binocular versus monocular response amplitude
Comparing the binocular and monocular response amplitudes that were obtained in an interleaved manner during the phase tuning experiments also revealed differences in the degree of binocular interactions in normal and treated monkeys. Figure 5 illustrates the frequency distributions for the ratio of the peak binocular response amplitude and the larger monocular response. In normal monkeys (top), the peak binocular response amplitude typically exceeded the larger monocular response, with ~70% of simple and complex cells showing some degree of binocular facilitation (ratios > 1.0). Both the prism- and lens-reared animals revealed a lower proportion of cells with high binocular-to-monocular response ratios. In other words, high degrees of binocular facilitation were less prevalent in the treated monkeys. For ratios near and <1.0, values that represent primarily monocular cells and cells that were suppressed by dichoptic stimulation, the simple cell distributions for all three subject groups were similar. However, in comparison with the normal and lens-reared monkeys, the prism-reared subjects also had a significantly greater proportion of complex cells that had peak binocular response amplitudes that were lower than their monocular response amplitudes (t-test,P < 0.001). Nearly 50% of the complex cells in prism-reared monkeys had peak-binocular-to-monocular ratios <1.0, which indicated that many complex cells were suppressed during binocular stimulation.

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| FIG. 5.
Frequency distributions of the ratio of the peak binocular response amplitude and the larger monocular response for simple (left) and complex (right) cells from normal (top), lens-reared (middle), and prism-reared (bottom) monkeys. Binocular response amplitudes were obtained from the sine functions fit to the phase tuning data (see Fig. 3).
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The reductions in the peak-binocular-to-monocular response ratios could have come about by a relative reduction in binocular response amplitude, an increase in the monocular response amplitude, or a combination of both changes. Comparing the monocular and peak binocular response amplitudes for the three subject groups (Fig. 6) suggests that the primary cause was a reduction in binocular response amplitude in the lens- and prism-reared monkeys. For both simple and complex cell populations, the average peak binocular response amplitudes were lower in the treated monkeys. On the other hand, the average monocular response rates were very similar for complex cells and only slightly smaller for simple cells in the treated animals.

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| FIG. 6.
Mean ± SD monocular response amplitudes for the dominant eyes (filled bars) and peak binocular response amplitudes (open bars) for simple (top) and complex (bottom) cells from the 3 subject groups.
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For non-phase-specific complex cells, the ratio of the mean binocular response to the larger monocular response is probably the most meaningful metric for comparing binocular and monocular responses. In normal monkeys, 77% of non-phase-specific complex cells exhibited mean-binocular-to-monocular response ratios >1.0 (i.e., cooperative binocular interactions, Fig. 7A). In contrast, the non-phase-specific complex cell population in the prism-reared monkeys included a high proportion of neurons with low mean-binocular-to-monocular response ratios (Fig. 7B); 71% of these cells had ratios <1.0 (indicating antagonistic binocular interactions), with many cells falling below the range for normals. Although two of the three prism-reared monkeys showed mild contrast sensitivity deficits at high spatial frequencies, there were no systematic differences in the degree of suppression found in cells dominated by the right versus left eyes. Taking into consideration that many of the cells that have ratios near 1.0 are truly monocular, there is a near absence in the prism-reared monkeys of binocular non-phase-specific complex cells showing binocular facilitation. In contrast, the distribution of non-phase-specific complex cells for the lens-reared animals peaks near 1.0, reflecting the relatively high number of monocular neurons. However, the distribution is more symmetrical than that in the prism-reared monkeys, with approximately equal proportions of complex cells showing binocular suppression versus binocular facilitation.

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| FIG. 7.
Frequency distributions of the ratio of the mean binocular response to the larger monocular response for complex cells that had BII values <0.3. Both the binocular and monocular response amplitudes were obtained during the dichoptic phase tuning experiments. A-C: data from normal, prism-reared, and lens-reared monkeys, respectively.
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Binocular combination of contrast signals
Binocular interactions in V1 neurons of normal animals appear to largely reflect the linear combination of inputs from the two eyes before a series of nonlinear mechanisms (Ohzawa and Freeman 1986a
,b
; Smith et al. 1997a
). We examined the manner in which contrast signals were combined in our treated animals with anomalous binocular vision by measuring binocular summation contours for individual cortical neurons. The general experimental protocol is illustrated in Fig. 8 for a simple cell from a lens-reared animal (see Smith et al. 1997a
). In the phase tuning experiment (Fig. 8A), the neuron exhibited a high degree of disparity tuning (BII = 1.05, signal-to-noise ratio = 5.65) and both binocular facilitation and suppression. The dichoptic contrast response functions (Fig. 8B) were measured for stimulus pairs that had right- to left-eye contrast ratios that ranged from 3.16 to 0.316. The dichoptic stimuli incorporated the optimal monocular spatial parameters and an optimal relative interocular spatial phase of 90°. The left- and right-eye contrast components required to produce a criterion response amplitude of 10 spikes/s were determined from hyperbolic functions {response (C) = R*max·[Cn/(Cn + Cn50)]} fitto the data for each interocular contrast ratio and plotted in Fig. 8C. The resulting binocular interaction contour was reasonably fit by a straight line (r2 = 0.82). In this coordinate space, data that conform to a straight line indicate that the contrast signals required to produce the criterion response amplitude were combined in simple linear manner.

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| FIG. 8.
Binocular interaction data for a representative simple cell from a lens-reared animal. A: phase tuning function measured with the use of the optimal stimulus orientations and spatial frequency (see Fig. 3 for details). B: contrast response functions obtained for monocular left-eye ( ) and right-eye ( ) stimuli and for dichoptic grating pairs that had different interocular contrast ratios (filled symbols). Filled squares, base-down triangles, base-up triangles, diamonds, and hexagons: right eye/left eye ratios of 3.16/1.0, 1.76/1.0, 1.0/1.0, 1.0/1.76, and 1.0/3.16, respectively. Stimulus orientation was optimal for each eye; spatial frequency was optimal for the dominant eye; and for all of the dichoptic stimuli, the relative interocular spatial phase was set at an optimal value of 90°. C: binocular interaction contour that was derived from the contrast response functions for a criterion response amplitude of 10 spikes/s (B, - - -). Abscissa and ordinate: right- and left-eye contrast components at threshold, respectively. Filled circles: threshold stimuli for each interocular contrast ratio. Solid line was determined by linear regression (r2 = 0.82).
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Binocular contrast summation was investigated in 21 neurons from the treated monkeys. Figure 9 illustrates the binocular interaction contours measured for six representative cells. As in normal monkeys (Smith et al. 1997a
), the interaction contours for both simple and complex cells in both the lens- and prism-reared animals were all well fit by a linear model (r2 ranged from 0.76 to 0.94). For cells that showed additive binocular interactions, the interaction contours had negative slopes (Fig. 9, A, B, D, and E). Cells that exhibited binocular suppression had interaction contours with positive slopes (Fig. 19, C and F). The key point is that the in all cases the contrast signals from the two eyes were combined in a linear fashion.

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| FIG. 9.
Binocular interaction contours for 6 representative neurons from lens-reared (left) and prism-reared (right) monkeys. A-D: data for simple cells. E and F: functions for complex cells. r2 values are the coefficients of determination obtained via linear regression analysis.
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DISCUSSION |
The main findings obtained from our treated monkeys were as follows. 1) Many cells that could only be excited by monocular stimuli presented to one eye showed robust binocular interactions for dichoptic stimuli. 2) In surviving binocular cells the contrast signals from the two eyes were combined in a normal linear manner and the residual binocular interactions were qualitatively normal. 3) The surviving binocular neurons showed lower degrees of binocular facilitation due to a selective reduction in binocular response amplitude. 4) The degree of disparity tuning in surving binocular neurons, particularly complex cells, was lower than normal. 5) A higher proportion of complex cells in the prism-reared monkeys exhibited binocular suppression for all dichoptic stimuli.
Basis for residual binocular interactions
Many aspects of cortical binocular interaction in our treated monkeys can be explained by an overall reduction in the functional excitatory inputs from one eye, as observed in many previous investigations of early abnormal visual experience (Movshon and Kiorpes 1990
). However, it is important to emphasize that in one sense measures of ocular dominance overestimate the loss of cortical binocular interactions because many neurons that failed to be excited by monocular stimuli presented to one eye showed clear functional inputs from the nondominant eye with dichoptic stimulation.
Anomalies in the spatial organization of a cell's monocular receptive fields can also explain many aspects of our subjects' residual binocular interactions. Movshon et al. (1987)
have argued that the anomalous monocular response properties of cortical neurons in monkeys reared with unilateral blur can be explained in large part by alterations in the spatial precision of the inputs that form a cell's receptive field. According to the hypothesis of Movshon et al., early abnormal visual experience disrupts the anatomically precise convergence of inputs onto a given cell. As a consequence, the normally precise spatial arrangement of excitatory and inhibitory inputs, which are thought to endow cells with a high degree of sensitivity for stimulus position, spatial frequency, and orientation (Ferster 1987
, 1988
; Movshon et al. 1978
), would be disrupted. In simple cells, scrambling the inputs to one or both receptive fields would disrupt the spatial organization of the composite binocular receptive field and thus potentially reduce the maximum binocular response amplitude and the cell's sensitivity to interocular phase disparities. Binocular phase tuning in complex cells would be particularly vulnerable to abnormal visual experience because in complex cells disparity sensitivity probably reflects an orderly convergence of binocular phase-tuned subunits onto a single complex unit (Ohzawa and Freeman 1986b
). Thus phase tuning would prevail only if the binocular receptive field organization in each individual subunit and the orderly spatial convergence of these subunits onto a given complex cell were unaffected by abnormal visual experience. With scrambled inputs, cells could have relatively balanced ocular dominances but lower than normal BII values, as frequently observed in complex cells in the lens-reared monkeys. Although disrupting the spatial orderliness of a receptive field would degrade a cell's monocular and binocular tuning properties, it would still allow linear spatial summation within the disrupted receptive field (Ohzawa and Freeman 1988
) and, as found in this study, between the receptive fields in the two eyes.
Binocular suppression
As previously found in strabismic kittens (Chino et al. 1994
; Sengpiel and Blakemore 1994
), our prism-reared monkeys exhibited an abnormally high proportion of non-phase-specific neurons that were dominated by suppressive binocular interactions. The high prevalence of binocular suppression is one aspect of the residual binocular interactions that cannot easily be attributed to a nonselective reduction in the functional inputs from one eye or a disruption in the spatial aspects of a cell's receptive fields.
The response latency of cortical units stimulated via the deviating eyes of strabismic kittens is abnormally long (Chino et al. 1983
; Eschweiler and Raushecker 1993
; Freeman and Tsumoto 1983
; Singer et al. 1980
). If similar latency changes occur in monkeys, it is possible that signals from the eye with the shorter latency could initiate intracortical inhibitory processes that would antagonize the signals from the eye with the longer latency (Eschweiler and Raushecker 1993
). In this scenario, it would be necessary for the suppressive inputs to come from a spatially diffuse set of neurons with receptive fields blanketing the classical receptive field of the cell under study. Consequently, the suppression would be initiated over a large area in a non-phase-specific manner.
It is possible that binocular suppression is the predominant binocular interaction because early strabismus alters the balance of intracortical excitatory and inhibitory inputs to a cell (see Katz and Calloway 1992
). For example, strabismus may selectively reduce excitatory connections, both local and long range (Löwel and Singer 1992
; Singer 1996
; Tychsen and Burkhalter 1995
), while sparing inhibitory connections. Sengpiel and Blakemore (1994)
have argued that differences in the specificity of connections between excitatory and inhibitory intracortical circuits could lead to a selective reduction in excitatory projections (also see Chino et al. 1994
). Horizontal excitatory connections appear to make reciprocal connections between cortical neurons that have similar response properties (Ts'o et al. 1986
; Welikey et al. 1995
), whereas intracortical inhibitory projections appear to contact neurons in a non-orientation-specific manner (Bonds 1989
; Somogyi et al. 1983
; however, see Welikey et al. 1995
). Possibly this higher degree of specificity makes excitatory connections more susceptible to abnormal visual experience. In this respect, Singer (1977)
has reported that electrically evoked polysynaptic binocular inhibitory responses are less susceptible to abnormal visual experience than excitatory responses.
Behavioral correlates of anomalous cortical binocularity
The binocular deficits in strabismus are generally more extensive than those found in anisometropic amblyopes and have been attributed primarily to the effects of prolonged suppression initiated by diplopia and confusion (von Noorden 1990
). Humans with long-standing, early-onset strabismus typically show dramatic reductions in binocular summation and stereopsis at all spatial frequencies (Harwerth and Levi 1983
; Lema and Blake 1977
; Levi et al. 1979
). Likewise, behavioral investigations demonstrated that the prism-reared monkeys employed in this study could not detect figures embedded in random-dot stereograms and failed to show binocular summation over a wide range of spatial frequencies, even when interocular differences in contrast sensitivity were taken into account. Moreover, recent psychophysical experiments in our lab have also demonstrated that prism-reared monkeys exhibit binocular suppression under normal viewing conditions (Wensveen et al. 1996
). The phenomenon of binocular suppression occurs in anisometropes as well, but both the degree and distribution of suppression across the visual field are more prominent in human strabismics, particularly in the absence of amblyopia (Holopigian et al. 1988
; Sireteanu 1982
; Sireteanu and Fronius 1981
). In this regard, the most striking differences between the prism-reared monkeys and either normal monkeys or our lens-reared monkeys was the high prevalence of non-phase-specific suppression. A virtual absence of non-phase-specific facilitation in complex cells, together with the increased prevalence of non-phase-specific suppression, could account for the prominence of behavioral binocular suppression in strabismic individuals under normal viewing conditions.
In comparison with the lens-reared monkeys, the prism-reared monkeys also exhibited a greater overall reduction in the degree of binocular interactions, with very few cells exhibiting a high degree of disparity sensitivity. The few phase-sensitive neurons that remained in V1 were evidently not sufficient to support stereoscopic depth judgments in random-dot stereograms; however, these cells may still have provided critical information on image disparities. For example, detection of image disparities is needed to make appropriate vergence eye movements and to maintain normal interocular alignment. In this respect, eye alignment estimates obtained with the use of corneal reflex techniques revealed that all of our prism-reared animals were orthotropic. And recent psychophysical investigations of motor fusion limits have revealed that monkeys subjected to short periods of early strabismus have significant stereo deficiencies but maintain relatively normal disparity vergence eye movements (Harwerth et al. 1997
). Possibly the remaining phase-sensitive neurons provided critical disparity information to the motor system and were somehow less susceptible to the optical effects of strabismus than those involved in stereodetection.
Overall, there are many parallels between the cortical binocular interactions found in our lens- and prism-reared monkeys and the residual binocular vision of humans with anisometropia or strabismus. Our results clearly support the idea that the neurophysiological basis for many of the binocular vision deficits in both strabismic and anisometropic individuals resides in V1.
 |
ACKNOWLEDGEMENTS |
We thank W. Ridder and K. Kitagawa for help in some of the recording experiments.
This work was supported by National Institutes of Health Grants EY-03611, EY-08128, EY-01139l, and RR-07146 and the Greeman-Petty Professorship of the University of Houston Endowment.
 |
FOOTNOTES |
Address reprint requests to E. L. Smith.
Received 22 March 1996; accepted in final form 21 May 1997.
 |
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