Binocular deficits associated with early alternating monocular defocus. II. Neurophysiological observations

Experiencing binocularly conflicting signals early in life dramatically alters the binocular responses of cortical neurons. Because visual cortex is highly plastic during a critical period of development, cortical deficits resulting from early abnormal visual experience often mirror the nature of interocular decorrelation of neural signals from the two eyes. In the preceding paper, we demonstrated that monkeys that experienced early alternating monocular defocus (-1.5, -3.0, or -6.0 D) show deficits in stereopsis that generally reflected the magnitude of imposed monocular defocus. Because these results indicated that alternating monocular defocus affected the higher spatial frequency components of visual scenes more severely, we employed microelectrode recording methods to investigate whether V1 neurons in these lens-reared monkeys exhibited spatial-frequency-dependent alterations in their binocular response properties. We found that a neuron\u27s sensitivity to interocular spatial phase disparity was reduced in the treated monkeys and that this reduction was generally more severe for units tuned to higher spatial frequencies. In the majority of the affected units, the disparity-sensitivity loss was associated with interocular differences in monocular receptive field properties. The present results suggest that the behavioral deficits in stereopsis produced by abnormal visual experience reflect at least in part the constraints imposed by alterations at the earliest stages of binocular cortical processing and support the hypothesis that the local disparity processing mechanisms in primates are spatially tuned and can be independently compromised by early abnormal visual experience

Early monocular defocus disrupts the normal development of receptive-field structure in V2 neurons of macaque monkeys

Experiencing different quality images in the two eyes soon after birth can cause amblyopia, a developmental vision disorder. Amblyopic humans show the reduced capacity for judging the relative position of a visual target in reference to nearby stimulus elements (position uncertainty) and often experience visual image distortion. Although abnormal pooling of local stimulus information by neurons beyond striate cortex (V1) is often suggested as a neural basis of these deficits, extrastriate neurons in the amblyopic brain have rarely been studied using microelectrode recording methods. The receptive field (RF) of neurons in visual area V2 in normal monkeys is made up of multiple subfields that are thought to reflect V1 inputs and are capable of encoding the spatial relationship between local stimulus features. We created primate models of anisometropic amblyopia and analyzed the RF subfield maps for multiple nearby V2 neurons of anesthetized monkeys by using dynamic two-dimensional noise stimuli and reverse correlation methods. Unlike in normal monkeys, the subfield maps of V2 neurons in amblyopic monkeys were severely disorganized: subfield maps showed higher heterogeneity within each neuron as well as across nearby neurons. Amblyopic V2 neurons exhibited robust binocular suppression and the strength of the suppression was positively correlated with the degree of hereogeneity and the severity of amblyopia in individual monkeys. Our results suggest that the disorganized subfield maps and robust binocular suppression of amblyopic V2 neurons are likely to adversely affect the higher stages of cortical processing resulting in position uncertainty and image distortion

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

Increased ‘noise’ in V2 neurons of amblyopic monkeys

Purpose:Experiencing early strabismus or chronic monocular defocus due to anisometropia often causes amblyopia unless treated early. Besides reduced acuity and contrast sensitivity, a broad range of more complex spatial and temporal vision deficits have been reported in amblyopes. Increased neural noise in their visual brain has been proposed as one of the sources for reduced visual functions (Levi, 2013). Here we investigated the possible origin of increased internal noise in non-human primates with anisometropic amblyopia. Methods:We recorded from multiple nearby neurons in Visual Area V2 of adult monkeys reared with monocular defocus between 3 weeks and 3 months of age and developed moderate ansiometropic amblyopia. Stimuli were drifting gratings (3.1 Hz) that were optimized for orientation, spatial frequency, and size for each neuron and were presented at low (25%) and high (80%) contrast for 100 times. For individual neurons, the variance of inter-spike intervals and variance to mean ratio (VMR) of spike counts were calculated. For multiple neurons recorded at the same site, noise correlation was computed. Results:1) There was no difference in variance of inter-spike interval among neurons driven by the amblyopic eye, those driven by the fellow eye, and normal V2 neurons. 2) With low contrast stimuli, the VMR (trial-to-trial fluctuation) was significantly elevated in V2 neurons driven by both the amblyopic and fellow eyes compared to that in normal monkeys. With high contrast gratings, there was no difference. 3) Noise correlation in amblyopic monkeys was significantly higher than that in normal monkeys at both low and high contrasts. Conclusions:Our results suggest that the more variable (noisy) responses of individual neurons and the elevated noise correlation in V2 of amblyopic monkeys, combined with abnormal response dynamics and disorganized subfield structures of V2 neurons, may affect signal processing down stream, which in turn may limit their visual performance

Brief Daily Periods of Unrestricted Vision Preserve Stereopsis in Strabismus

In this study, stereopsis was preserved in optically strabismic infant monkeys by brief daily periods of normal binocular vision. This result indicates that the temporal integration properties of mechanisms responsible for vision development ensure that binocular vision development proceeds normally despite episodes of abnormal vision, but also implies that stereopsis may be preserved in human strabismic infants by providing brief daily periods of fusion prior to alignment surgery

Effects of Brief Daily Periods of Unrestricted Vision during Early Monocular Form Deprivation on Development of Visual Area 2

Daily brief periods of unrestricted vision during early monocular form deprivation reduced the impact of amblyopia, and this preventive effect was most closely associated with reduced ocular dominance imbalance and binocular suppression in V2

Comparisons of the spatial matrix of subfields between multiple nearby V2 neurons in amblyopic monkeys

Amblyopia is a developmental vision deficit caused by experiencing binocular imbalance during early development. Despite some interesting theories based on many perceptual and modeling studies, the neural basis of vision deficits associated with amblyopia is poorly understood except for the well established ocular dominance imbalance in V1 of monocularly form deprived animals. In this study we employed a new approach to study vision deficits in amblyopic monkeys that may give us an insight into a neural basis of position uncertainty, distortion, and/or deficit orientation discrimination in human amblyopes. We simulated anisometropic amblyopia by having infant macaque monkeys wear defocusing lens in one eye between 3 weeks and 3 months of age. When they matured we obtained their spatial contrast sensitivity functions to determine the depth of amblyopia. We recorded action potentials from multiple nearby units with a single electrode. We employed dynamic two dimensional noise stimuli and a reverse correlation (LSRC) method to reveal subfields within the receptive field of each V2 neuron. The spatial maps of these subfields were compared between multiple nearby neurons with respect to their preferred orientations, spatial frequencies, and the maximal strength of responses. We quantified the heterogeneity of the subfield maps (heterogeneity index) for each unit (within comparison) and between units (across-unit comparison). We found that 1) in normal monkeys, the heterogeneity index was very low both within a given unit and across nearby units. 2) In amblyopic monkeys, for the within-unit comparison, the heterogeneity index of the subfield maps driven by the amblyopic eye was similar to that for the fellow eye, but both were slightly but significantly higher than in normal monkeys. 3) For the across-units comparison, the heterogeneity index of the subfield maps of V2 neurons for the amblyopic eye was far greater than that for the fellow eye, while the index for the fellow eye was also significantly greater than that in normal monkeys. 4) The abnormally high heterogeneity indices in amblyopic monkeys did not result from weak or noisy responses in amblyopic monkeys. 5) V2 neurons of amblyopic monkeys exhibited robust binocular suppression when dichoptic sine wave gratings were used for stimuli. The results suggest that the fine circuitry supporting the feed forward connections from V1 to V2 and the local connections within V2 appear to be disrupted in amblyopic monkeys, and that robust binocular suppression may be involved, at least in part, with the abnormally large differences in the subfield maps of multiple nearby units in amblyopic monkeys