Ocular dominance-dependent binocular combination of monocular neuronal responses in macaque V1.

Primates rely on two eyes to perceive depth, while maintaining stable vision when either one eye or both eyes are open. Although psychophysical and modeling studies have investigated how monocular signals are combined to form binocular vision, the underlying neuronal mechanisms, particularly in V1 where most neurons exhibit binocularity with varying eye preferences, remain poorly understood. Here, we used two-photon calcium imaging to compare the monocular and binocular responses of thousands of simultaneously recorded V1 superficial-layer neurons in three awake macaques. During monocular stimulation, neurons preferring the stimulated eye exhibited significantly stronger responses compared to those preferring both eyes. However, during binocular stimulation, the responses of neurons preferring either eye were suppressed on the average, while those preferring both eyes were enhanced, resulting in similar neuronal responses irrespective of their eye preferences, and an overall response level similar to that with monocular viewing. A neuronally realistic model of binocular combination, which incorporates ocular dominance-dependent divisive interocular inhibition and binocular summation, is proposed to account for these findings.

Reduced Monocular Luminance Promotes Fusion But Not Mixed Perception in Amblyopia.

Purpose: The purpose of this study was to understand how monocular luminance reduction affects binocular balance and examine whether it differentially influences fusion and mixed perception in amblyopia. Methods: Twenty-three normally sighted observers and 12 adults with amblyopia participated in this study. A novel binocular rivalry task was used to measure the phase duration of four perceptual responses (right- and left-tilts, fusion, and mixed perception) before and after a neutral density (ND) filter was applied at various levels to the dominant eye (DE) of controls and the fellow eye (FE) of patients with amblyopia. Phase durations were analyzed to assess whether the duration of fusion or mixed perception shifted after monocular luminance reduction. Moreover, we quantified ocular dominance and adjusted monocular contrast and luminance separately to investigate the relationship between changes in ocular dominance induced by the two manipulations. Results: In line with previous studies, binocular balance shifted in favor of the brighter eye in both normal adults and patients with amblyopia. As a function of the ND filter's density, the duration of fusion and mixed perception decreased in normal controls, whereas that of fusion but not mixed perception increased significantly in patients with amblyopia. In addition, changes in binocular balance from luminance reduction were more significant in more balanced amblyopes or normal observers. Furthermore, shifts in binocular balance after contrast and luminance modulation were correlated in both normal and amblyopic observers. Conclusions: The duration of fusion but not mixed perception increased in amblyopia after monocular luminance reduction in the FE. Moreover, our findings demonstrate that changes in ocular dominance from contrast-modulation and luminance-modulation are correlated in both normal and amblyopic observers.

Causal role of the frontal eye field in attention-induced ocular dominance plasticity.

Previous research has found that prolonged eye-based attention can bias ocular dominance. If one eye long-termly views a regular movie meanwhile the opposite eye views a backward movie of the same episode, perceptual ocular dominance will shift towards the eye previously viewing the backward movie. Yet it remains unclear whether the role of eye-based attention in this phenomenon is causal or not. To address this issue, the present study relied on both the functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) techniques. We found robust activation of the frontal eye field (FEF) and intraparietal sulcus (IPS) when participants were watching the dichoptic movie while focusing their attention on the regular movie. Interestingly, we found a robust effect of attention-induced ocular dominance shift when the cortical function of vertex or IPS was transiently inhibited by continuous theta burst stimulation (cTBS), yet the effect was significantly attenuated to a negligible extent when cTBS was delivered to FEF. A control experiment verified that the attenuation of ocular dominance shift after inhibitory stimulation of FEF was not due to any impact of the cTBS on the binocular rivalry measurement of ocular dominance. These findings suggest that the fronto-parietal attentional network is involved in controlling eye-based attention in the 'dichoptic-backward-movie' adaptation paradigm, and in this network, FEF plays a crucial causal role in generating the attention-induced ocular dominance shift.

Daily dose-response from short-term monocular deprivation in adult humans.

Short-term monocular deprivation (MD) shifts sensory eye balance in favour of the previously deprived eye. The effect of MD on eye balance is significant but brief in adult humans. Recently, researchers and clinicians have attempted to implement MD in clinical settings for adults with impaired binocular vision. Although the effect of MD has been studied in detail in single-session protocols, what is not known is whether the effect of MD on eye balance deteriorates after repeated periods of MD (termed 'perceptual deterioration'). An answer to this question is relevant for two reasons. Firstly, the effect of MD (i.e., dose-response) should not decrease with repeated use if MD is to be used therapeutically (e.g., daily for weeks). Second, it bears upon the question of whether the neural basis of the effects of MD and contrast adaptation, a closely related phenomenon, is the same. The sensory change from contrast adaptation depends on recent experience. If the observer has recently experienced the same adaptation multiple times for consecutive days, then the adaptation effect will be smaller because contrast adaptation exhibits perceptual deterioration, so it is of interest to know if the effects of MD follow suit. This study measured the effect of 2-h MD for seven consecutive days on binocular balance of 15 normally sighted adults. We found that the shift in eye balance from MD stayed consistent, showing no signs of deterioration after subjects experienced multiple periods of MD. This finding shows no loss of effectiveness of repeated daily doses of MD if used therapeutically to rebalance binocular vision in otherwise normal individuals. Furthermore, ocular dominance plasticity, which is the basis of the effects of short-term MD, does not seem to share the property of 'perceptual deterioration' with contrast adaptation, suggesting different neural bases for these two related phenomena.

A developmental critical period for ocular dominance plasticity of binocular neurons in mouse superior colliculus.

Detecting visual features in the environment is crucial for animals' survival. The superior colliculus (SC) is implicated in motion detection and processing, whereas how the SC integrates visual inputs from the two eyes remains unclear. Using in vivo electrophysiology, we show that mouse SC contains many binocular neurons that display robust ocular dominance (OD) plasticity in a critical period during early development, which is similar to, but not dependent on, the primary visual cortex. NR2A- and NR2B-containing N-methyl-D-aspartate (NMDA) receptors play an essential role in the regulation of SC plasticity. Blocking NMDA receptors can largely prevent the impairment of predatory hunting caused by monocular deprivation, indicating that maintaining the binocularity of SC neurons is required for efficient hunting behavior. Together, our studies reveal the existence and function of OD plasticity in SC, which broadens our understanding of the development of subcortical visual circuitry relating to motion detection and predatory hunting.

Adaptation of Ocular Opponency Neurons Mediates Attention-Induced Ocular Dominance Plasticity.

Previous research has shown that ocular dominance can be biased by prolonged attention to one eye. The ocular-opponency-neuron model of binocular rivalry has been proposed as a candidate account for this phenomenon. Yet direct neural evidence is still lacking. By manipulating the contrast of dichoptic testing gratings, here we measured the steady-state visually evoked potentials (SSVEPs) at the intermodulation frequencies to selectively track the activities of ocular-opponency-neurons before and after the "dichoptic-backward-movie" adaptation. One hour of adaptation caused a shift of perceptual and neural ocular dominance towards the unattended eye. More importantly, we found a decrease in the intermodulation SSVEP response after adaptation, which was significantly greater when high-contrast gratings were presented to the attended eye than when they were presented to the unattended eye. These results strongly support the view that the adaptation of ocular-opponency-neurons contributes to the ocular dominance plasticity induced by prolonged eye-based attention.

Ocular dominance in cataract surgery: research status and progress.

Ocular dominance (OD), a commonly used concept in clinical practice, plays an important role in optometry and refractive surgery. With the development of refractive cataract surgery, the refractive function of the intraocular lens determines the achievement of the postoperative full range of vision based on the retinal defocus blur suppression and binocular monovision principle. Therefore, OD plays an important role in cataract surgery. OD is related to the visual formation of the cerebral cortex, and its plasticity suggests that visual experience can influence the visual system. Cataract surgery changes the visual experience and transforms the dominant eye, which confirms the plasticity of the visual system. Based on the concept and mechanism of OD, this review summarizes the application of OD in cataract surgery.

Active vision gates ocular dominance plasticity in human adults.

Primary visual cortex (V1) retains a form of plasticity in adult humans: a brief period of monocular deprivation induces an enhanced response to the deprived eye, which can stabilize into a consolidated plastic change1,2 despite unaltered thalamic input3. This form of homeostatic plasticity in adults is thought to act through neuronal competition between the representations of the two eyes, which are still separate in primary visual cortex4,5. During monocular occlusion, neurons of the deprived eye are thought to increase response gain given the absence of visual input, leading to the post-deprivation enhancement. If the decrease of reliability of the monocular response is crucial to establish homeostatic plasticity, this could be induced in several different ways. There is increasing evidence that V1 processing is affected by voluntary action, allowing it to take into account the visual effects of self-motion6, important for efficient active vision7. Here we asked whether ocular dominance homeostatic plasticity could be elicited without degrading the quality of monocular visual images but simply by altering their role in visuomotor control by introducing a visual delay in one eye while participants actively performed a visuomotor task; this causes a discrepancy between what the subject sees and what he/she expects to see. Our results show that homeostatic plasticity is gated by the consistency between the monocular visual inputs and a person's actions, suggesting that action not only shapes visual processing but may also be essential for plasticity in adults.

The Suppressive Basis of Ocular Dominance Changes Induced by Short-Term Monocular Deprivation in Normal and Amblyopic Adults.

Purpose: We aimed to study the effect of short-term monocular deprivation on the suppressive interocular interactions in normals and amblyopes by using a dichoptic masking paradigm. Methods: Nine adults with anisometropic or mixed amblyopia and 10 control adults participated in our study. The contrast sensitivity in discriminating a target Gabor dichoptically masked was measured before and after 2 hours of monocular deprivation. The mask consisted of bandpass-filtered noise. Both the target and the mask were horizontally oriented at the spatial frequency of 1.31 cpd. Deprivation was achieved using an opaque patch on the amblyopic eye of amblyopes and the dominant eye of controls. Results: Results were similar in both controls and amblyopes. After 2 hours of monocular deprivation, the previously patched eye showed a significant increase in contrast sensitivity under dichoptic masking, which also suggested reduced suppressive effect from the nonpatched eye. Meanwhile, the contrast sensitivity of the nonpatched eye remained almost unchanged under dichoptic masking. Conclusions: We demonstrate that the ocular dominance changes induced by short-term monocular deprivation-namely, the strengthening of the deprived eye's contribution-are associated with the unilateral and asymmetric changes in suppressive interaction. The suppression from the nondeprived eye is reduced after short-term monocular deprivation. This provides a better understanding of how inverse patching (patching of the amblyopic eye) could, by reducing the suppressive drive from the normally sighted (nondeprived) eye, form the basis of a new treatment for the binocular deficit in amblyopia.

Thalamic regulation of ocular dominance plasticity in adult visual cortex.

Experience-dependent plasticity in the adult visual system is generally thought of as a cortical process. However, several recent studies have shown that perceptual learning or monocular deprivation can also induce plasticity in the adult dorsolateral geniculate nucleus (dLGN) of the thalamus. How plasticity in the thalamus and cortex interact in the adult visual system is ill-understood. To assess the influence of thalamic plasticity on plasticity in primary visual cortex (V1), we made use of our previous finding that during the critical period ocular dominance (OD) plasticity occurs in dLGN and requires thalamic synaptic inhibition. Using multielectrode recordings we find that this is also true in adult mice, and that in the absence of thalamic inhibition and plasticity, OD plasticity in adult V1 is absent. To study the influence of V1 on thalamic plasticity, we silenced V1 and show that during the critical period, but not in adulthood, the OD shift in dLGN is partially caused by feedback from V1. We conclude that during adulthood the thalamus plays an unexpectedly dominant role in experience-dependent plasticity in V1. Our findings highlight the importance of considering the thalamus as a potential source of plasticity in learning events that are typically thought of as cortical processes.

Measuring the reliability of binocular rivalry.

Binocular rivalry is a widely used tool in sensory and cognitive neuroscience to investigate different aspects of vision and cognition. The dynamics of binocular rivalry (e.g., duration of perceptual dominance phases and mixed percept proportions) differ across individuals; based on rivalry dynamics, it is also possible to calculate an index of ocular dominance (by comparing the perceptual dominance of the images in the two eyes). In this study, we investigated the reliability of binocular rivalry dynamics using different methods for dichoptic stimulation and different rivalry stimuli. For the three main indices we defined (ocular dominance, phase durations and mixed percept proportions), we found a high test-retest reliability across sessions. Moreover, the test-retest reliability of the ocular dominance index was predictable from its internal consistency, supporting its stability over time. Phase durations and mixed percept proportions, in contrast, had worse test-retest reliability than expected based on internal consistency, indicating that these parameters are susceptible to state-dependent changes. Our results support the use of the ocular dominance index and binocular rivalry in the measurement of sensory eye dominance and its plasticity, but advise caution when investigating the association between phase durations or mixed percepts and stable characteristics like psychological traits or disorders.

Integration and suppression interact in binocular vision.

Contingent on stereo compatibility, two images presented dichoptically can lead to either binocular integration, thus generating stable stereopsis, or interocular suppression that induces binocular rivalry with bistable perception that alternates between the two images. The relationship between binocular integration and interocular suppression concerns how our brain processes binocular inputs to form unified visual awareness but remains unclear. Here, a series of psychophysical experiments were conducted to address this question, revealing that these collaborative and competitive binocular interactions are interconnected and would mediate one another according to their strength. Specifically, Experiments 1a and 1b showed that the presence of binocular rivalry inhibited peripheral stereopsis, significantly elevating the stereo threshold, with higher elevation resulting from increasing rivalry contrast. Experiments 2a and 2b showed that existing stereopsis with increasing binocular disparity balanced the dynamics of peripheral binocular rivalry, rendering more equivalent eye dominance. Based on these interactions, we suggest that binocular integration and interocular suppression may mediate one another through an overlapping mechanism for regulating eye dominance, with strong stereo percepts tending to reduce eye dominance and strong rivalry tending to increase eye dominance.

A role for ocular dominance in binocular integration.

Neurons in the primate primary visual cortex (V1) combine left- and right-eye information to form a binocular output. Controversy surrounds whether ocular dominance, the preference of these neurons for one eye over the other, is functionally relevant. Here, we demonstrate that ocular dominance impacts gain control during binocular combination. We recorded V1 spiking activity while monkeys passively viewed grating stimuli. Gratings were either presented to one eye (monocular), both eyes with the same contrasts (binocular balanced), or both eyes with different contrasts (binocular imbalanced). We found that contrast placed in a neuron's dominant eye was weighted more strongly than contrast placed in a neuron's non-dominant eye. This asymmetry covaried with neurons' ocular dominance. We then tested whether accounting for ocular dominance within divisive normalization improves the fit to neural data. We found that ocular dominance significantly improved model performance, with interocular normalization providing the best fits. These findings suggest that V1 ocular dominance is relevant for response normalization during binocular stimulation.

Prevalence of refractive error in Portugal – A systematic review and meta-analysis

Purpose The aim of this study was to systematically review and meta-analyse epidemiological data of refractive error prevalence in Portugal. Methods A structured search strategy and systematic literature review was applied to multiple databases, such as MEDLINE/PubMed, Web of Science, Scopus, Google Scholar, official organizations and academic repositorium's, to identify all relevant epidemiological studies in Portugal until February 2021. The outcome measure was the prevalence of refractive error among the Portuguese population. The events and sample size were entered as raw data and the effect size parameters were computed by Comprehensive Meta-Analysis Software. Results A total of 9 studies were pooled for the meta-analysis. The fixed effects model points to an estimated effect size of 43% (95% CI: 41.9–44.1%). However, the statistics of heterogeneity (Q-value p < 0.001; I-squared =99.344) showed very high heterogeneity among studies and recommends using a random-effects model. The random effects model points to an estimated effect size of 31.9% (95% CI: 19.8–47.0%) prevalence of refractive error in the Portuguese population. Conclusions A prevalence of refractive error in Portugal of 31.9% (95% CI: 20.0–47.0%) can be considered as a conservative approach to the real burden of this condition. However, it translates into at least 2 to 4.5 million Portuguese individuals with a refractive error. The high heterogeneity between studies, the wide estimate and the random effects involved demonstrate the need for more studies and consistent sources to obtain narrower estimates. (AU)

Metaplasticity: Dark exposure boosts local excitability and visual plasticity in adult human cortex.

An interlude of dark exposure for about 1 week is known to shift excitatory/inhibitory (E/I) balance of the mammalian visual cortex, promoting plasticity and accelerating visual recovery in animals that have experienced cortical lesions during development. However, the translational impact of our understanding of dark exposure from animal studies to humans remains elusive. Here, we used magnetic resonance spectroscopy as a probe for E/I balance in the primary visual cortex (V1) to determine the effect of 60 min of dark exposure, and measured binocular combination as a behavioural assay to assess visual plasticity in 14 normally sighted human adults. To induce neuroplastic changes in the observers, we introduced 60 min of monocular deprivation, which is known to temporarily shift sensory eye balance in favour of the previously deprived eye. We report that prior dark exposure for 60 min strengthens local excitability in V1 and boosts visual plasticity in normal adults. However, we show that it does not promote plasticity in amblyopic adults. Nevertheless, our findings are surprising, given the fact that the interlude is very brief. Interestingly, we find that the increased concentration of the excitatory neurotransmitter is not strongly correlated with the enhanced functional plasticity. Instead, the absolute degree of change in its concentration is related to the boost, suggesting that the dichotomy of cortical excitation and inhibition might not explain the physiological basis of plasticity in humans. We present the first evidence that an environmental manipulation that shifts cortical E/I balance can also act as a metaplastic facilitator for visual plasticity in humans. KEY POINTS: A brief interlude (60 min) of dark exposure increased the local concentration of glutamine/glutamate but not that of GABA in the visual cortex of adult humans. After dark exposure, the degree of the shift in sensory eye dominance in favour of the previously deprived eye from short-term monocular deprivation was larger than that from only monocular deprivation. The neurochemical and behavioural measures were associated: the magnitude of the shift in the concentration of glutamine/glutamate was correlated with the boost in perceptual plasticity after dark exposure. Surprisingly, the increase in the concentration of glutamine/glutamate was not correlated with the perceptual boost after dark exposure, suggesting that the physiological mechanism of how E/I balance regulates plasticity is not deterministic. In other words, an increased excitation did not unilaterally promote plasticity.

Widespread and Multifaceted Binocular Integration in the Mouse Primary Visual Cortex.

The brain combines two-dimensional images received from the two eyes to form a percept of three-dimensional surroundings. This process of binocular integration in the primary visual cortex (V1) serves as a useful model for studying how neural circuits generate emergent properties from multiple input signals. Here, we perform a thorough characterization of binocular integration using electrophysiological recordings in the V1 of awake adult male and female mice by systematically varying the orientation and phase disparity of monocular and binocular stimuli. We reveal widespread binocular integration in mouse V1 and demonstrate that the three commonly studied binocular properties-ocular dominance, interocular matching, and disparity selectivity-are independent of each other. For individual neurons, the responses to monocular stimulation can predict the average amplitude of binocular response but not its selectivity. Finally, the extensive and independent binocular integration of monocular inputs is seen across cortical layers in both regular-spiking and fast-spiking neurons, regardless of stimulus design. Our data indicate that the current model of simple feedforward convergence is inadequate to account for binocular integration in mouse V1, thus suggesting an indispensable role played by intracortical circuits in binocular computation.SIGNIFICANCE STATEMENT Binocular integration is an important step of visual processing that takes place in the visual cortex. Studying the process by which V1 neurons become selective for certain binocular disparities is informative about how neural circuits integrate multiple information streams at a more general level. Here, we systematically characterize binocular integration in mice. Our data demonstrate more widespread and complex binocular integration in mouse V1 than previously reported. Binocular responses cannot be explained by a simple convergence of monocular responses, contrary to the prevailing model of binocular integration. These findings thus indicate that intracortical circuits must be involved in the exquisite computation of binocular disparity, which would endow brain circuits with the plasticity needed for binocular development and processing.

Subtractive adaptation is a more effective and general mechanism in binocular rivalry than divisive adaptation.

The activity of neurons is influenced by random fluctuations and can be strongly modulated by firing rate adaptation, particularly in sensory systems. Still, there is ongoing debate about the characteristics of neuronal noise and the mechanisms of adaptation, and even less is known about how exactly they affect perception. Noise and adaptation are critical in binocular rivalry, a visual phenomenon where two images compete for perceptual dominance. Here, we investigated the effects of different noise processes and adaptation mechanisms on visual perception by simulating a model of binocular rivalry with Gaussian white noise, Ornstein-Uhlenbeck noise, and pink noise, in variants with divisive adaptation, subtractive adaptation, and without adaptation. By simulating the nine models in parameter space, we find that white noise only produces rivalry when paired with subtractive adaptation and that subtractive adaptation reduces the influence of noise intensity on rivalry strength and introduces convergence of the mean percept duration, an important metric of binocular rivalry, across all noise processes. In sum, our results show that white noise is an insufficient description of background activity in the brain and that subtractive adaptation is a stronger and more general switching mechanism in binocular rivalry than divisive adaptation, with important noise-filtering properties.

A laminar model for the joint development of ocular dominance columns and CO blobs in the primary visual cortex.

In this paper, we present a multi-layer, activity-dependent model for the joint development of ocular dominance (OD) columns and cytochrome oxidase (CO) blobs in primate V1. For simplicity, we focus on layers 4C and 2/3 with both layers receiving direct thalamic inputs and layer 4C sending vertical projections to layer 2/3. Both the thalamic and the vertical connections are taken to be modifiable by activity. Using a correlation-based Hebbian learning rule with subtractive normalization, we show how the formation of an OD map in layer 4C is inherited by layer 2/3 via the vertical projections. Competition between these feedforward projections and the direct thalamic input to layer 2/3 then results in the formation of CO blobs superimposed upon the ocular dominance map. The spacing of the OD columns is determined by the spatial profile of the intralaminar connections within layer 4, while the spacing of CO blobs depends both on the width of the OD columns inherited from layer 4 and the spatial distribution of intralaminar connections within the superficial layer. The resulting CO blob distribution is shown to be consistent with experimental data. In addition, we numerically simulate monocular deprivation and find that while the CO blob distribution is unaltered, the OD pattern undergoes modification. The OD stripes of the deprived eye narrow, whereas the OD stripes for the remaining open eye widen.

Visual experience-dependent development of ocular dominance columns in pigmented rats.

Despite previous agreement of the absence of cortical column structure in the rodent visual cortex, we have recently revealed a presence of ocular dominance columns (ODCs) in the primary visual cortex (V1) of adult Long-Evans rats. In this study, we deepened understanding of characteristics of rat ODCs. We found that this structure was conserved in Brown Norway rats, but not in albino rats; therefore, it could be a structure generally present in pigmented wild rats. Activity-dependent gene expression indicated that maturation of eye-dominant patches takes more than 2 weeks after eye-opening, and this process is visual experience dependent. Monocular deprivation during classical critical period strongly influenced size of ODCs, shifting ocular dominance from the deprived eye to the opened eye. On the other hand, transneuronal anterograde tracer showed a presence of eye-dominant patchy innervation from the ipsilateral V1 even before eye-opening, suggesting the presence of visual activity-independent genetic components of developing ODCs. Pigmented C57BL/6J mice also showed minor clusters of ocular dominance neurons. These results provide insights into how visual experience-dependent and experience-independent components both contribute to develop cortical columns during early postnatal stages, and indicate that rats and mice can be excellent models to study them.

Different Forms of Plasticity Interact in Adult Humans.

Neuroplasticity is maximal during development and declines in adulthood, especially for sensory cortices. On the other hand, the motor and prefrontal cortices retain plasticity throughout the lifespan. This difference has led to a modular view of plasticity in which different brain regions have their own plasticity mechanisms that do not depend or translate on others. Recent evidence shows that visual and motor plasticity share common neural mechanisms (e.g., GABAergic inhibition), indicating a possible link between these different forms of plasticity, however, the interaction between visual and motor plasticity has never been tested directly. Here, we show that when visual and motor plasticity are elicited at the same time in adult humans, visual plasticity is impaired, while motor plasticity is spared. Moreover, simultaneous activation of working memory and visual plasticity also leads to impairment in visual plasticity. These unilateral interactions between visual, working memory, and motor plasticity demonstrate a clear link between these three forms of plasticity. We conclude that local neuroplasticity in separate systems might be regulated globally, to preserve overall homeostasis in the brain.