Labile nature of the visual recovery promoted by reverse occlusion in monocularly deprived kittens.

Kittens were monocularly deprived by closing one eye at the time of natural eye opening for periods that ranged from 4 to 14 weeks. This eye was then opened, and the other eye was closed for an approximately equal period of time. During this period of reverse occlusion, the vision of the initially deprived eye improved from apparent blindness to a level of good visual acuity. Surprisingly, however, this recovery was largely eliminated in only 2 weeks once the initially nondeprived eye was opened to restore visual input to both eyes. This finding has important implications for the nature of the mechanism(s) responsible for the dramatic physiological effects of monocular occlusion on the visual cortex. It may also help to elucidate recent observations on patching therapy in human amblyopia.     

Temporal events in cyclopean vision.

The majority of neurons in the primary visual cortex of primates can be activated by stimulation of either eye; moreover, the monocular receptive fields of such neurons are located in about the same region of visual space. These well-known facts imply that binocular convergence in visual cortex can explain our cyclopean view of the world. To test the adequacy of this assumption, we examined how human subjects integrate binocular events in time. Light flashes presented synchronously to both eyes were compared to flashes presented alternately (asynchronously) to one eye and then the other. Subjects perceived very-low-frequency (2 Hz) asynchronous trains as equivalent to synchronous trains flashed at twice the frequency (the prediction based on binocular convergence). However, at higher frequencies of presentation (4-32 Hz), subjects perceived asynchronous and synchronous trains to be increasingly similar. Indeed, at the flicker-fusion frequency (approximately 50 Hz), the apparent difference between the two conditions was only 2%. We suggest that the explanation of these anomalous findings is that we parse visual input into sequential episodes.     

Binocular vision in older people with adventitious visual impairment: sometimes one eye is better than two

PURPOSE: To determine the effect of adventitious visual impairment (low vision) on monocular and binocular spatial contrast sensitivity of older people. DESIGN: A between-within repeated measures design. PARTICIPANTS: Fifty-nine older adults between the ages of 50 and 96; 49 of the observers had age-related macular degeneration (AMD). MEASURES: Visual acuity screening and spatial contrast sensitivity. RESULTS: In almost half of the population with AMD, the sensitivity to spatial information, as measured by spatial contrast sensitivity, is worse when both eyes are used than when the stimuli are viewed with only one eye. This "binocular inhibition" is not related to the contrast sensitivity of the better eye or to acuities. Furthermore, this inhibition process is reflected primarily in images with medium to low spatial frequency components (medium to large size bars). CONCLUSIONS: These results have important implications for understanding the functional impact of low vision in older people. They suggest that almost one-half of older people with AMD view the world best using only one of their eyes, whereas for the other half, there is an advantage to using binocular vision for certain visual tasks.     

Neural correlates of perceptual learning: a functional MRI study of visual texture discrimination

Visual texture discrimination has been shown to induce long-lasting behavioral improvement restricted to the trained eye and trained location in visual field [Karni, A. & Sagi, D. (1991) Proc. Natl. Acad. Sci. USA 88, 4966-4970]. We tested the hypothesis that such learning involves durable neural modifications at the earliest cortical stages of the visual system, where eye specificity, orientation, and location information are mapped with highest resolution. Using functional magnetic resonance imaging in humans, we measured neural activity 24 h after a single session of intensive monocular training on visual texture discrimination, performed in one visual quadrant. Within-subject comparisons between trained and untrained eye for targets presented within the same quadrant revealed higher activity in a corresponding retinotopic area of visual cortex. Functional connectivity analysis showed that these learning-dependent changes were not associated with an increased engagement of other brain areas remote from early visual cortex. We suggest that these new data are consistent with recent proposals that the cellular mechanisms underlying this type of perceptual learning may involve changes in local connections within primary visual cortex. Our findings provide a direct demonstration of learning-dependent reorganization at early processing stages in the visual cortex of adult humans.     

Schwann cells transplanted in the lateral ventricles prevent the functional and anatomical effects of monocular deprivation in the rat.

We investigated whether the transplant of Schwann cells prevents the physiological and morphological effects of monocular deprivation in the rat. On the day of eye opening in rats (postnatal day 14), we transplanted Schwann cells in the lateral ventricles and sutured the eyelids of one eye. After 20-30 days, at the end of the critical period for the visual system development, we analyzed the functional properties of visual cortical neurons. Spontaneous discharge, orientation selectivity, and receptive field size of visual cortical neurons in transplanted animals were in the normal range. Transplantation of Schwann cells prevented the detrimental effects of monocular deprivation on ocular dominance and binocularity of cortical neurons. Visual acuity of the deprived eye estimated by visually evoked potentials was also normal. Schwann cells derived from adult animals were as effective as those derived from neonates. The effects of Schwann cells on monocular deprivation were dependent upon the number of cells present in the transplant so that 10(6) Schwann cells were sufficient to prevent the effect of monocular deprivation, whereas 10(5) and 3.3 x 10(5) Schwann cells were ineffective, and 6.3 x 10(5) cells gave variable results. Shrinkage of the deprived lateral geniculate neurons was prevented by a transplant of 10(6) cells. In rats transplanted with hybridoma cells producing an antibody that functionally blocks nerve growth factor (NGF), we found that the effect of cotransplanted Schwann cells on monocular deprivation was partly counteracted. We conclude that transplantation of Schwann cells prevents both functional and anatomical effects of monocular deprivation, presumably acting through the production of NGF. We propose that transplants of Schwann cells could be a promising technique for clinical applications.     

Rapid experience-dependent plasticity of synapse function and structure in ferret visual cortex in vivo

The rules by which visual experience influences neuronal responses and structure in the developing brain are not well understood. To elucidate the relationship between rapid functional changes and dendritic spine remodeling in vivo, we carried out chronic imaging experiments that tracked visual responses and dendritic spines in the ferret visual cortex following brief periods of monocular deprivation. Functional changes, which were largely driven by loss of deprived eye responses, were tightly regulated with structural changes at the level of dendritic spines, and occurred very rapidly (on a timescale of hours). The magnitude of functional changes was correlated with the magnitude of structural changes across the cortex, and both these features reversed when the deprived eye was reopened. A global rule governed how the responses to the two eyes or changes in spines were altered by monocular deprivation: the changes occurred irrespective of regional ocular dominance preference and were independently mediated by each eye, and the loss or gain of responses/spines occurred as a constant proportion of predeprivation drive by the deprived or nondeprived eye, respectively.     

Coexistence of binocular integration and suppression determined by surface border information

The visual system relies on both the integration and interocular inhibitory processes to achieve single vision from different images in the two eyes. It is generally assumed that the integration process first searches for matching local features between the two eyes. If the matching fails, an interocular inhibitory process is triggered to suppress the image representation of one eye, leading to visual perception that is essentially contributed by the other eye. Here, using a stimulus comprising of binocularly corresponding features (vertical gratings) but incompatible surface border information, we found evidence to the contrary. In one half-image, a circular patch of vertical grating was phase-shifted relative to the surrounding vertical grating to create a circular, monocular boundary contour (MBC), while the other half-image had a similar vertical grating. The two half-images had a binocular disparity at the circular grating patch area, leading to the percept of a disc in depth. Concurrent with the stereo percept, threshold for detecting a Gabor probe on the half-image without the MBC was higher than that on the corresponding area with the grating disc, indicating binocular suppression. These findings reveal that when we perceive depth, which requires the integration process to obtain binocular disparity from the two eyes, one eye''s image could simultaneously be suppressed from visual awareness by the interocular inhibitory process. Our study also presents a provocative example of where the brain selectively binds some, but not all, features of the images from the two eyes for visual perception.     

Prediction of improved vision in the amblyopic eye after visual loss in the non-amblyopic eye

Amblyopia arises from abnormal visual experiences in early childhood. Improved function of the amblyopic eye after visual loss in the non-amblyopic eye could be a model for residual neural plasticity. We aimed to establish the likelihood of, and predictive factors for, this improvement in function. We identified 254 individuals aged 11 years or older with unilateral amblyopia who were visually impaired after loss of vision in their non-amblyopic eye but had no other disorder affecting their amblyopic eye. 25 (10%) of 254 people had improved visual acuity in their amblyopic eye. These findings suggest there is some plasticity in the visual system of a few visually mature individuals with amblyopia, which warrants further study. Children should remain the focus of detection and treatment.     

A correlational model for the development of disparity selectivity in visual cortex that depends on prenatal and postnatal phases.

Neurons in the visual cortex require correlated binocular activity during a critical period early in life to develop normal response properties. We present a model for how the disparity selectivity of cortical neurons might arise during development. The model is based on Hebbian mechanisms for plasticity at synapses between geniculocortical neurons and cortical cells. The model is driven by correlated activity in retinal ganglion cells within each eye before birth and additionally between eyes after birth. With no correlations present between the eyes, the cortical model developed only monocular cells. Adding a small amount of correlation between eyes at the beginning of development produced cortical neurons that were entirely binocular and tuned to zero disparity. However, if an initial phase of purely same-eye correlations was followed by a second phase of development that included correlations between eyes, the cortical model became populated with both monocular and binocular cells. Moreover, in the two-phase model, binocular cells tended to be selective for zero disparity, whereas the more monocular cells tended to have nonzero disparity. This relationship between ocular dominance and disparity has been observed in the visual cortex of the cat by other workers. Differences in the relative timing of the two developmental phases could account for the higher proportion of monocular cells found in the visual cortices of other animals.     

Changes in protein synthesis underlying functional plasticity in immature monkey visual system

Local rates of cerebral protein synthesis were determined in newborn rhesus monkeys subjected to either acute or chronic monocular visual deprivation. Chronic monocular deprivation resulted in decreased rates of protein synthesis in the laminae of the lateral geniculate nuclei innervated by the deprived eye whereas rates of protein synthesis were normal in geniculate laminae innervated by the functioning eye. Acute monocular deprivation produced no differential changes in rates of protein synthesis in any of the geniculate laminae.     

A rich environmental experience reactivates visual cortex plasticity in aged rats

Brain aging is characterized by functional deterioration across multiple systems, associated to a progressive decay of neural plasticity. Here, we explored environmental enrichment (EE), a condition of enhanced sensory-motor and cognitive stimulation, as a strategy to restore plasticity processes in the old brain. Visual system is one of the paradigmatic models for studying experience-dependent plasticity. While reducing input from one eye through monocular deprivation induces a marked ocular dominance (OD) shift of neurons in the primary visual cortex during development, the same manipulation is totally ineffective after the closure of the critical period. We show that EE is able to reactivate OD plasticity in the visual cortex of aging rats, as assessed with both visual-evoked potentials and single-unit recordings. A marked reduction in intracortical GABAergic inhibition and a remodeling of extracellular matrix accompany this effect. The non-invasive nature of EE makes this paradigm eligible for human application.     

Indirect costs associated with accessing eye care services as a barrier to service use in Ethiopia

BACKGROUND: The prevalence of blindness and visual impairment are high in Ethiopia and use of services is limited. Determining the barriers to use of eye care services is critical for planning strategies to prevent blindness. METHODS: A population-based survey of the magnitude and causes of blindness and visual impairment in adults 40 years and older in the Gurage Zone, central Ethiopia was conducted. Among those individuals who had binocular or monocular vision <6/18, an interview to assess use of eye care services and reasons for a failure to use such services was undertaken. RESULTS: Of 850 adults with visual impairment or blindness, 802 were interviewed. Cataract surgery accounted for the primary service currently needed by the blind, followed by trichiasis surgery; service needs were higher for women than for men. Use of services (27.8% of sample) was associated with being male, binocular vision loss, and blindness. The primary reason for a failure to use eye care services were indirect costs (overall, reported by 40% of respondents) associated with accessing the service. There were significant differences between men and women in the reasons for not using the services and between cataract and trichiasis cases but not when comparing binocular vs. monocular conditions, or patients with visual impairment vs. blindness. CONCLUSION: The majority of the causes of visual impairment and blindness are treatable (cataract) or preventable (trachomatous trichiasis). The main barrier for seeking service is related to the indirect medical costs of the service. This suggests that efforts are needed to create mechanisms that 'bridge' communities and eye care facilities. A holistic approach that deals both with the organization of services and the sociocultural factors in communities that affect use is needed. The organization of trichiasis surgery at peripheral health centres and screening programmes which identify and facilitate transport to hospital for cataract patients is one approach. The indirect burden of accessing eye care on the family may be lessened by encouraging patients to have surgery earlier (before they require assistance to reach the hospital), and by improving the efficiency of existing services. Promotion of services must be gender-sensitive, ensuring that specific characteristics of the sociocultural roles of women be considered in order to improve uptake among women. Training and placement of cataract surgeons in rural hospitals would also enhance provision of eye care for the rural population.     

Nerve growth factor-induced ocular dominance plasticity in adult cat visual cortex.

Activity-dependent modifiability of cortical ocular dominance occurs only during early postnatal life, within the so-called "critical period," but not thereafter in adult visual cortex. To examine the role of neurotrophins in the activity- and age-dependent stimulation-induced modifiability of visual cortex, we tested whether intracortical infusion of nerve growth factor could induce ocular dominance plasticity in adult visual cortex. Nerve growth factor was continuously infused, by means of osmotic minipumps, into striate cortex of adult cats for 2 weeks. At the time of minipump implantation, one eyelid of the experimental animals was sutured closed. After 3 weeks of monocular deprivation, the ocular dominance distribution of neurons in the striate cortex was assessed using single unit recording. We found that monocular deprivation imposed on adult animals in conjunction with nerve growth factor infusion causes an ocular dominance shift toward the deprived eye. Although the underlying mechanisms remain uncertain, the results indicate that nerve growth factor can enhance activity-dependent synaptic modification and remodeling in adult visual cortex.     

Neural plasticity without postsynaptic action potentials: less-active inputs become dominant when kitten visual cortical cells are pharmacologically inhibited.

Models of synaptic plasticity in the nervous system have conventionally assumed a mechanism in which spike activity of a postsynaptic cell enhances the efficacy of recently active presynaptic inputs. Making use of the prompt and dramatic response of the visual cortex to occlusion of vision in one eye during the critical period, we tested the role of postsynaptic activity in ocular dominance plasticity. To do so, we selectively blocked cortical cell discharges with a continuous intracortical infusion of the inhibitory neurotransmitter agonist muscimol during a period of monocular deprivation. This drug inhibits cortical cell discharges with no apparent effect on the activity of their presynaptic geniculocortical inputs. Recording from single cortical cells after they had recovered from the muscimol-induced blockade, we found a consistent shift in the responsiveness of the visual cortex in favor of the less-active, closed eye, while the normal shift in favor of the more-active, open eye was evident in regions not affected by the treatment. Such an inhibition-coupled expression of plasticity in favor of the less-active, closed eye cannot be explained by a nonspecific disruption of cortical function. We interpret these results to indicate (i) that the postsynaptic cell is crucially involved in plasticity of the visual cortex, (ii) that the direction of cortical plasticity depends on postsynaptic membrane conductance or polarization, and (iii) that plasticity can occur in the absence of postsynaptic spike activity.     

Binocular competition in the control of geniculate cell size depends upon visual cortical N-methyl-D-aspartate receptor activation.

The lateral geniculate nucleus relays visual information from the retina to cortex. One well-known anatomical consequence of monocular deprivation during early postnatal development is a shrinkage of neurons in the lamina of the lateral geniculate nucleus that receive input from the deprived eye. This is thought to reflect the competition of afferents subserving the two eyes, possibly at the level of the visual cortex. We find that blockade of N-methyl-D-aspartate receptors in kitten visual cortex disrupts this process of binocular competition. These data provide direct evidence that postsynaptic activation of cortical neurons is required for competitive changes in lateral geniculate cell size and suggest a role for N-methyl-D-aspartate receptors in anatomical as well as physiological plasticity in the mammalian visual system.     

Nerve growth factor prevents the amblyopic effects of monocular deprivation.

Monocular deprivation early in life causes dramatic changes in the functional organization of mammalian visual cortex and severe reduction in visual acuity and contrast sensitivity of the deprived eye. We tested whether or not these changes could be from competition between the afferents from the two eyes for a target-derived neurotrophic factor. Rats monocularly deprived during early postnatal development were treated with repetitive intraventricular injections or topical administration of nerve growth factor. The effects of monocular deprivation were then assessed electrophysiologically. In untreated animals visual acuity and contrast sensitivity of the deprived eye were strongly reduced, whereas in nerve growth factor-treated animals these parameters were normal.     

Initial recovery of vision after early monocular deprivation in kittens is faster when both eyes are open

A comparison was made of the speed of visual recovery in the deprived eye of kittens after a 6-day period of monocular deprivation imposed at 5-9 weeks of age in two postdeprivation conditions. In one condition, binocular recovery (BR), both eyes were open, whereas in the other condition, reverse lid-suture (RLS), the formerly nondeprived eye was closed to force the animal to use the originally deprived eye. In littermate pairs, BR kittens began to recover form vision 12 to 30 h before those subjected to RLS. The vision of the deprived eye of the BR animals remained superior to that of their RLS littermates for 4-8 days. Although this finding is difficult to reconcile with competitive mechanisms of synaptic plasticity, it supports a prediction of an alternative model of synaptic plasticity [Bienenstock, E. L., Cooper, L. N. & Munro, P. W. (1982) J. Neurosci. 2, 32-48] for slower initial recovery with RLS because of the time required to reset the modification threshold.     

When the brain changes its mind: Interocular grouping during binocular rivalry

The prevalent view of binocular rivalry holds that it is a competition between the two eyes mediated by reciprocal inhibition among monocular neurons. This view is largely due to the nature of conventional rivalry-inducing stimuli, which are pairs of dissimilar images with coherent patterns within each eye’s image. Is it the eye of origin or the coherency of patterns that determines perceptual alternations between coherent percepts in binocular rivalry? We break the coherency of conventional stimuli and replace them by complementary patchworks of intermingled rivalrous images. Can the brain unscramble the pieces of the patchwork arriving from different eyes to obtain coherent percepts? We find that pattern coherency in itself can drive perceptual alternations, and the patchworks are reassembled into coherent forms by most observers. This result is in agreement with recent neurophysiological and psychophysical evidence demonstrating that there is more to binocular rivalry than mere eye competition.     

Experience-dependent regulation of CaMKII activity within single visual cortex synapses in vivo

Unbalanced visual input during development induces persistent alterations in the function and structure of visual cortical neurons. The molecular mechanisms that drive activity-dependent changes await direct visualization of underlying signals at individual synapses in vivo. By using a genetically engineered Förster resonance energy transfer (FRET) probe for the detection of CaMKII activity, and two-photon imaging of single synapses within identified functional domains, we have revealed unexpected and differential mechanisms in specific subsets of synapses in vivo. Brief monocular deprivation leads to activation of CaMKII in most synapses of layer 2/3 pyramidal cells within deprived eye domains, despite reduced visual drive, but not in nondeprived eye domains. Synapses that are eliminated in deprived eye domains have low basal CaMKII activity, implying a protective role for activated CaMKII against synapse elimination.     

Transient monocular blindness

An attack of abrupt loss of vision in one eye that recovers completely after a short period is called "transient monocular blindness" (TMB) or amaurosis fugax. The most common cause of TMB is atherothromboembolism from the origin of the internal carotid artery (ICA), whereas atrial fibrillation is quite uncommon. TMB also can be caused by anterior optic nerve ischemia, that is usually caused by thrombosis in the posterior ciliary artery. Thrombosis in the central retinal vein may be another cause. Dissection of the ICA, vascular malformations, or fibromuscular dysplasia are other potential etiologies. Blurring of vision as compared with blackened vision or positive phenomena such as flashing is probably associated with a higher risk of future cardiovascular events, whereas involvement of the partial monocular field is associated with a relative benign prognosis. In patients with atherosclerosis, antiplatelet therapy is indicated and treatment of vascular risk factors should have high priority. Carotid endarterectomy should be performed only in case of an ICA stenosis of more than 70% in the presence of at least one other risk factor for stroke.