Deficits In Visual Function Research Articles

Visual defects in a mouse model of fetal alcohol spectrum disorder.

Alcohol consumption during pregnancy can lead to a multitude of neurological problems in offspring, varying from subtle behavioral changes to severe mental retardation. These alterations are collectively referred to as Fetal Alcohol Spectrum Disorders (FASD). Early alcohol exposure can strongly affect the visual system and children with FASD can exhibit an amblyopia-like pattern of visual acuity deficits even in the absence of optical and oculomotor disruption. Here, we test whether early alcohol exposure can lead to a disruption in visual acuity, using a model of FASD to mimic alcohol consumption in the last months of human gestation. To accomplish this, mice were exposed to ethanol (5 g/kg i.p.) or saline on postnatal days (P) 5, 7, and 9. Two to three weeks later we recorded visually evoked potentials to assess spatial frequency detection and contrast sensitivity, conducted electroretinography (ERG) to further assess visual function and imaged retinotopy using optical imaging of intrinsic signals. We observed that animals exposed to ethanol displayed spatial frequency acuity curves similar to controls. However, ethanol-treated animals showed a significant deficit in contrast sensitivity. Moreover, ERGs revealed a market decrease in both a- and b-waves amplitudes, and optical imaging suggest that both elevation and azimuth maps in ethanol-treated animals have a 10–20° greater map tilt compared to saline-treated controls. Overall, our findings suggest that binge alcohol drinking restricted to the last months of gestation in humans can lead to marked deficits in visual function.

Retinal Damage in Chloroquine Maculopathy, Revealed by High Resolution Imaging: A Case Report Utilizing Adaptive Optics Scanning Laser Ophthalmoscopy

A 53-year-old Asian woman was treated with hydroxychloroquine and chloroquine for lupus erythematosus. Within a few years, she noticed circle-shaped shadows in her central vision. Upon examination, the patient's visual acuity was 20 / 25 in both eyes. Humphrey visual field (HVF) testing revealed a central visual defect, and fundoscopy showed a ring-shaped area of parafoveal retinal pigment epithelium depigmentation. Fundus autofluorescence imaging showed a hypofluorescent lesion consistent with bull's eye retinopathy. Adaptive optics scanning laser ophthalmoscope (AO-SLO) revealed patch cone mosaic lesions, in which cones were missing or lost. In addition, the remaining cones consisted of asymmetrical shapes and sizes that varied in brightness. Unlike previous studies employing deformable mirrors for wavefront aberration correction, our AO-SLO approach utilized dual liquid crystal on silicon spatial light modulators. Thus, by using AO-SLO, we were able to create a photographic montage consisting of high quality images. Disrupted cone AO-SLO images were matched with visual field test results and functional deficits were associated with a precise location on the montage, which allowed correlation of histological findings with functional changes determined by HVF. We also investigated whether adaptive optics imaging was more sensitive to anatomical changes compared with spectral-domain optical coherence tomography.

When apperceptive agnosia is explained by a deficit of primary visual processing

Visual agnosia is a deficit in shape perception, affecting figure, object, face and letter recognition. Agnosia is usually attributed to lesions to high-order modules of the visual system, which combine visual cues to represent the shape of objects. However, most of previously reported agnosia cases presented visual field (VF) defects and poor primary visual processing. The present case-study aims to verify whether form agnosia could be explained by a deficit in basic visual functions, rather that by a deficit in high-order shape recognition. Patient SDV suffered a bilateral lesion of the occipital cortex due to anoxia. When tested, he could navigate, interact with others, and was autonomous in daily life activities. However, he could not recognize objects from drawings and figures, read or recognize familiar faces. He was able to recognize objects by touch and people from their voice. Assessments of visual functions showed blindness at the centre of the VF, up to almost 5°, bilaterally, with better stimulus detection in the periphery. Colour and motion perception was preserved. Psychophysical experiments showed that SDV's visual recognition deficits were not explained by poor spatial acuity or by the crowding effect. Rather a severe deficit in line orientation processing might be a key mechanism explaining SDV's agnosia. Line orientation processing is a basic function of primary visual cortex neurons, necessary for detecting “edges” of visual stimuli to build up a “primal sketch” for object recognition. We propose, therefore, that some forms of visual agnosia may be explained by deficits in basic visual functions due to widespread lesions of the primary visual areas, affecting primary levels of visual processing.

Driving and off‐road impairments underlying failure on road testing in Parkinson's disease

Parkinson's disease (PD) affects driving ability. We aimed to determine the most critical impairments in specific road skills and in clinical characteristics leading to failure on a road test in PD. In this cross-sectional study, certified driving assessment experts evaluated specific driving skills in 104 active, licensed drivers with PD using a standardized, on-road checklist and issued a global decision of pass/fail. Participants also completed an off-road evaluation assessing demographic features, disease characteristics, motor function, vision, and cognition. The most important driving skills and off-road predictors of the pass/fail outcome were identified using multivariate stepwise regression analyses. Eighty-six (65%) passed and 36 (35%) failed the on-road driving evaluation. Persons who failed performed worse on all on-road items. When adjusted for age and gender, poor performances on lateral positioning at low speed, speed adaptations at high speed, and left turning maneuvers yielded the best model that determined the pass/fail decision (R(2) = 0.56). The fail group performed poorer on all motor, visual, and cognitive tests. Measures of visual scanning, motor severity, PD subtype, visual acuity, executive functions, and divided attention were independent predictors of pass/fail decisions in the multivariate model (R(2) = 0.60). Our study demonstrated that failure on a road test in PD is determined by impairments in specific driving skills and associated with deficits in motor, visual, executive, and visuospatial functions. These findings point to specific driving and off-road impairments that can be targeted in multimodal rehabilitation programs for drivers with PD.

Intact reading in patients with profound early visual dysfunction

Despite substantial neuroscientific evidence for a region of visual cortex dedicated to the processing of written words, many studies continue to reject explanations of letter-by-letter (LBL) reading in terms of impaired word form representations or parallel letter processing in favour of more general deficits of visual function. In the current paper, we demonstrate that whilst LBL reading is often associated with general visual deficits, these deficits are not necessarily sufficient to cause reading impairment and have led to accounts of LBL reading which are based largely on evidence of association rather than causation. We describe two patients with posterior cortical atrophy (PCA) who exhibit remarkably preserved whole word and letter reading despite profound visual dysfunction. Relative to controls, both patients demonstrated impaired performance on tests of early visual, visuoperceptual and visuospatial processing; visual acuity was the only skill preserved in both individuals. By contrast, both patients were able to read aloud words with perfect to near-perfect accuracy. Reading performance was also rapid with no overall significant difference in response latencies relative to age- and education-matched controls. Furthermore, the patients violated a key prediction of general visual accounts of LBL reading – that pre-lexical impairments should result in prominent word length effects; in the two reported patients, evidence for abnormal word length effects was equivocal or absent, and certainly an order of magnitude different to that reported for LBL readers. We argue that general visual accounts cannot explain the pattern of reading data reported, and attribute the preserved reading performance to preserved direct access to intact word form representations and/or parallel letter processing mechanisms. The current data emphasise the need for much clearer evidence of causality when attempting to draw connections between specific aspects of visual processing and different types of acquired peripheral dyslexia.

Measuring Visual Function in Diabetic Retinopathy: Progress in Basic and Clinical Research

Diabetic retinopathy is a common consequence of diabetes mellitus and the leading cause of vision loss in workingage people in the United States. The pathology of this disease is well characterized by microvascular lesions but also includes deficits in visual function, possibly as a consequence of retinal neurodegeneration. Microvasculature changes are clinically detected by fundus examination and used as the primary method of diagnosis, but functional tests may represent alternative endpoints that may be useful in translational research. Components of visual function can be characterized in a variety of different ways including measures of acuity, contrast sensitivity, dark adaptation and a number of electrophysiological parameters of the retina. This review discusses loss of function as measured both in human and animal models of diabetic retinopathy.

Chronic morphine exposure affects contrast response functions of V1 neurons in cats

Opiates disrupt neural functions in many brain areas, including visual cortex. Previous studies have indicated substantial changes of many neuronal response properties induced by chronic morphine exposure in the visual information processing system. However, it remains unclear whether neuronal contrast coding is also affected. To investigate this issue, we measured the contrast response functions (CRFs) of V1 neurons in chronic morphine-treated and saline-treated cats by using extra-cellular single-unit recording techniques. Our results indicated significantly lower contrast sensitivity in morphine-treated cats than in saline-treated cats and V1 neurons in morphine-treated cats exhibited enhanced maximum visual responses, higher baseline responses and lower signal-to-noise ratios compared with saline-treated cats. These findings provide some neurobiological evidence for the morphine-mediated degenerations of the visual cortex, which could underlie the opiate-induced deficits in visual function.

Complement Factor H Deficiency Results in Decreased Neuroretinal Expression ofCd59ain Aged Mice

The complement system is closely linked to the pathogenesis of AMD. Several complement genes are expressed in RPE, and complement proteins accumulate in drusen. Further, a common variant of complement factor H (CFH) confers increased risk of developing AMD. Because the mechanisms by which changes in the function of CFH influence development of AMD are unclear, we examined ocular complement expression as a consequence of age in control and CFH null mutant mice. Gene expression in neuroretinas and RPE/choroid from young and aged WT and Cfh(-/-) C57BL/6J mice was analyzed by microarrays. Expression of a wide range of complement genes was compared with expression in liver. An age-associated increased expression of complement, particularly C1q, C3, and factor B, in the RPE/choroid coincided with increased expression of the negative regulators Cfh and Cd59a in the neuroretina. Young mice deficient in CFH expressed Cd59a similar to WT, but failed to upregulate Cd59a expression with age. Hepatic expression of Cd59a increased with age regardless of Cfh genotype. While the connection between CFH deficiency and failure to upregulate CD59a remains unknown, these results suggest that expression of CD59 is tissue-specific and that neuroretinal regulation depends on CFH. This could contribute to the visual functional deficits and morphological changes in the Cfh(-/-) mouse retina that occur with age.

Cognition in nephropathic cystinosis: pattern of expression in heterozygous carriers.

Individuals with cystinosis exhibit specific cognitive deficits in visual spatial function. The purpose of the current study was to examine if obligate heterozygotes of the CTNS mutation have the same pattern of cognitive functioning seen in homozygotes, namely aberrant visual-spatial functioning against a background of relatively intact visual-perceptual functioning and overall cognitive ability. Study participants were 254 adults (100 heterozygotes and 154 controls), ages 17 years 10 months through 74 years 9 months. Tests of intelligence, visual perceptual, and visual spatial functioning were administered. Our results showed that cystinosis heterozygotes demonstrated intelligence within the normal range, and performed similarly to controls on tests of visual-perceptual ability. In contrast, the heterozygotes performed significantly more poorly on each of the visual-spatial tests when compared to controls. Obligate heterozygotes for the CTNS mutation display a similar pattern of visual processing decrements as do individuals with cystinosis. Namely, carriers demonstrate relative weaknesses in visual-spatial processing, while maintaining normal visual perceptual ability and intelligence in the normal range. The visual spatial decrements in heterozygotes were not as marked as those found in individuals with cystinosis, suggesting a gene dosing effect. This study provides an impetus for other studies of gene-behavior relationships in recessive disorders, and may stimulate further interest in the role of aberrant genes on "individual differences" in behavior.

Differential Effects of Unfolded Protein Response Pathways on Axon Injury-Induced Death of Retinal Ganglion Cells

Loss of retinal ganglion cells (RGCs) accounts for visual function deficits after optic nerve injury, but how axonal insults lead to neuronal death remains elusive. By using an optic nerve crush model that results in the death of the majority of RGCs, we demonstrate that axotomy induces differential activation of distinct pathways of the unfolded protein response in axotomized RGCs. Optic nerve injury provokes a sustained CCAAT/enhancer binding homologous protein (CHOP) upregulation, and deletion of CHOP promotes RGC survival. In contrast, IRE/XBP-1 is only transiently activated, and forced XBP-1 activation dramatically protects RGCs from axon injury-induced death. Importantly, such differential activations of CHOP and XBP-1 and their distinct effects on neuronal cell death are also observed in RGCs with other types of axonal insults, such as vincristine treatment and intraocular pressure elevation, suggesting a new protective strategy for neurodegeneration associated with axonal damage.

Multiple Electrophysiological Markers of Visual-Attentional Processing in a Novel Task Directed toward Clinical Use.

Individuals who have sustained a mild brain injury (e.g., mild traumatic brain injury or mild cerebrovascular stroke) are at risk to show persistent cognitive symptoms (attention and memory) after the acute postinjury phase. Although studies have shown that those patients perform normally on neuropsychological tests, cognitive symptoms remain present, and there is a need for more precise diagnostic tools. The aim of this study was to develop precise and sensitive markers for the diagnosis of post brain injury deficits in visual and attentional functions which could be easily translated in a clinical setting. Using electrophysiology, we have developed a task that allows the tracking of the processes involved in the deployment of visual spatial attention from early stages of visual treatment (N1, P1, N2, and P2) to higher levels of cognitive processing (no-go N2, P3a, P3b, N2pc, SPCN). This study presents a description of this protocol and its validation in 19 normal participants. Results indicated the statistically significant presence of all ERPs aimed to be elicited by this novel task. This task could allow clinicians to track the recovery of the mechanisms involved in the deployment of visual-attentional processing, contributing to better diagnosis and treatment management for persons who suffer a brain injury.

Simulated loss of foveal vision eliminates visual search advantage in repeated displays

In the contextual cueing paradigm, incidental visual learning of repeated distractor configurations leads to faster search times in repeated compared to new displays. This contextual cueing is closely linked to the visual exploration of the search arrays as indicated by fewer fixations and more efficient scan paths in repeated search arrays. Here, we examined contextual cueing under impaired visual exploration induced by a simulated central scotoma that causes the participant to rely on extrafoveal vision. We let normal-sighted participants search for the target either under unimpaired viewing conditions or with a gaze-contingent central scotoma masking the currently fixated area. Under unimpaired viewing conditions, participants revealed shorter search times and more efficient exploration of the display for repeated compared to novel search arrays and thus exhibited contextual cueing. When visual search was impaired by the central scotoma, search facilitation for repeated displays was eliminated. These results indicate that a loss of foveal sight, as it is commonly observed in maculopathies, e.g., may lead to deficits in high-level visual functions well beyond the immediate consequences of a scotoma.

Preterm birth: the ophthalmic consequences

Aim: There is a growing body of evidence evaluating the outcomes following preterm birth. Continued evaluation is essential to determine the impact of new treatments, which can affect many areas of development. Therefore this review aims to provide an evidence-based update on the ophthalmic sequelae of preterm birth. Methods: A literature search of databases was performed, focusing on publications from the last 3 years. Results: New treatments are being developed to prevent severe vision loss due to retinopathy of prematurity (ROP), but as they are so new no longterm data are available. The development of new imaging techniques has allowed detailed analysis of the visual pathway, with changes in the posterior visual pathway identified and linked to visual function. Deficits of visual function in the preterm population extend beyond visual acuity, affecting functional ability in many ways, even in the presence of a normal visual acuity response. Strabismus rates continue to be increased but do not appear to have changed in recent years. Overall the literature agrees that preterm birth affects a range of ophthalmic outcomes, but there continues to be a lack of consensus as to what follow-up care is required. Conclusions: Children born preterm are at continued risk of developing a range of ophthalmic sequelae but new techniques are being applied to determine their aetiology. Novel treatments for ROP have shown promise in reducing severe visual impairments, but many questions remain regarding the nature of more subtle deficits of visual functions and how they should be identified.

Quantification of Deficits in Spatial Visual Function of Mouse Models for Glaucoma

DBA/2J mice are a standard preclinical glaucoma model, which spontaneously developed mutations resulting in chronic age-related pigmentary glaucoma. The goals of this study were to identify the degree of visual impairment in DBA/2J mice before and after disease onset by quantifying the optokinetic reflex responses and to compare them to the less-researched strain of DBA/2NHsd mice. Visual performance was measured in healthy, nonglaucomatous, and glaucomatous male DBA/2NHsd or DBA/2J mice using a visuospatial testing box. The optokinetic reflex resulting in optomotor head tracking was manually detected. Measured threshold levels equate to the maximum contrast or spatial frequency the mouse responds to. Intraocular pressure (IOP) was measured by applanation tonometry. IOP increased with age in both DBA/2J and DBA/2NHsd mice and was not different between the two substrains. Both visual acuity and ability to detect contrast decreased significantly, and similarly with age in both substrains. However, DBA/2NHsd had poorer visual acuity even at a younger age compared to age-matched DBA/2J mice. Both DBA/2J and DBA/2NHsd mice show a progressive glaucomatous phenotype of age-related increases in IOP and loss of visual acuity and contrast sensitivity when compared to other inbred or outbred strains. Given the similar increases in IOP and contrast sensitivity threshold and loss of visual acuity between these two DBA/2 substrains, we also conclude that DBA/2NHsd mice are a suitable alternative model for pigmentary glaucoma.

The effects of acute alcohol exposure on the response properties of neurons in visual cortex area 17 of cats

Physiological and behavioral studies have demonstrated that a number of visual functions such as visual acuity, contrast sensitivity, and motion perception can be impaired by acute alcohol exposure. The orientation- and direction-selective responses of cells in primary visual cortex are thought to participate in the perception of form and motion. To investigate how orientation selectivity and direction selectivity of neurons are influenced by acute alcohol exposure in vivo, we used the extracellular single-unit recording technique to examine the response properties of neurons in primary visual cortex (A17) of adult cats. We found that alcohol reduces spontaneous activity, visual evoked unit responses, the signal-to-noise ratio, and orientation selectivity of A17 cells. In addition, small but detectable changes in both the preferred orientation/direction and the bandwidth of the orientation tuning curve of strongly orientation-biased A17 cells were observed after acute alcohol administration. Our findings may provide physiological evidence for some alcohol-related deficits in visual function observed in behavioral studies.

Electrophysiological and Histologic Assessment of Retinal Ganglion Cell Fate in a Mouse Model forOPA1-Associated Autosomal Dominant Optic Atrophy

The main disease features of autosomal dominant optic atrophy (ADOA) are a bilateral reduction of visual acuity, cecocentral scotoma, and frequently tritanopia, which have been ascribed to a progressive loss of retinal ganglion cells (RGCs) and subsequent degeneration of the optic nerve. The main disease-causing gene is OPA1. Here, we examine a mouse carrying a pathogenic mutation in Opa1 by electrophysiological measurements and assess the fate of RGCs. Two-year-old animals underwent a full examination by electroretinography (ERG) and visually evoked potential (VEP) measurements to assess the function of the outer and inner retina and the optic nerve. Retrograde Fluorogold labeling was performed to determine the number of surviving RGCs and to assess axonal transport by neurofilament counterstaining. Phagocytosis-dependent labeled microglial cells were identified by an Iba-1 staining. ERG responses were normal in aged Opa1 mice. VEP measurements revealed significantly reduced amplitudes but no change in the latencies in contrast to extended latencies found in glaucoma. Retrograde labeling of RGCs showed a significant reduction in the number of RGCs in Opa1 mice. Long-term experiments revealed the presence of microglial cells with ingested fluorescent dye. This is the first electrophysiological demonstration of a visual function deficit in aged Opa1 mice. VEP measurements and retrograde labeling experiments show that the number of RGCs is reduced whereas the remaining RGCs and axons function normally. Taken together, these findings support an ascending progress of degeneration from the soma toward the axon.

Sensory Contributions to Impaired Emotion Processing in Schizophrenia

Both emotion and visual processing deficits are documented in schizophrenia, and preferential magnocellular visual pathway dysfunction has been reported in several studies. This study examined the contribution to emotion-processing deficits of magnocellular and parvocellular visual pathway function, based on stimulus properties and shape of contrast response functions. Experiment 1 examined the relationship between contrast sensitivity to magnocellular- and parvocellular-biased stimuli and emotion recognition using the Penn Emotion Recognition (ER-40) and Emotion Differentiation (EMODIFF) tests. Experiment 2 altered the contrast levels of the faces themselves to determine whether emotion detection curves would show a pattern characteristic of magnocellular neurons and whether patients would show a deficit in performance related to early sensory processing stages. Results for experiment 1 showed that patients had impaired emotion processing and a preferential magnocellular deficit on the contrast sensitivity task. Greater deficits in ER-40 and EMODIFF performance correlated with impaired contrast sensitivity to the magnocellular-biased condition, which remained significant for the EMODIFF task even when nonspecific correlations due to group were considered in a step-wise regression. Experiment 2 showed contrast response functions indicative of magnocellular processing for both groups, with patients showing impaired performance. Impaired emotion identification on this task was also correlated with magnocellular-biased visual sensory processing dysfunction. These results provide evidence for a contribution of impaired early-stage visual processing in emotion recognition deficits in schizophrenia and suggest that a bottom-up approach to remediation may be effective.

Impaired perceptual networks in temporal lobe epilepsy revealed by resting fMRI

Viewed as a neural network disorder, mesial temporal lobe epilepsy (mTLE) may cause widespread deficits in human brain functions. Impairments in cognitive functions such as memory and language have been well addressed, but perceptual deficits have only been considered in terms of behavioral data. Little imaging research on perceptual deficits in mTLE has been reported. The present study is expected to reveal impairments in the perceptual networks in patients with mTLE using fMRI. The fMRI-based independent component analysis (ICA) was applied to 33 patients with mTLE and 33 matched healthy controls. In light of the resting-state networks (RSNs) corresponding to the basal functions of visual, auditory, and sensorimotor systems, the ICA data of functional connectivity within these RSNs were compared between the patients and controls. Compared with the controls, the mTLE patients presented decreased functional connectivity within the regions of the auditory and sensorimotor networks, as well increased functional connectivity in the primary visual cortex and decreased functional connectivity in the bilateral MT+ areas of the visual network. Our neuroimaging results are in agreement with the previous findings that specific perceptual functions are impaired in mTLE. Furthermore, our findings in the visual network support the belief that the primary visual function is not impaired and that there may be deficits in the high-order visual function in mTLE. Our fMRI study may contribute to the understanding of neuropathophysiological mechanisms underlying perceptual impairments in mTLE.

Aging affects contrast response functions and adaptation of middle temporal visual area neurons in rhesus monkeys

In the present study we studied the effects of aging on the coding of contrast in area V1 (primary visual cortex) and MT (middle temporal visual area) of the macaque monkey using single-neuron in vivo electrophysiology. Our results show that both MT and V1 neurons in old monkeys are less sensitive to contrast than those in young monkeys. Generally, contrast sensitivity is affected by aging more severely in MT cells than in V1 cells. Specifically, MT cells were affected more severely than motion direction selective V1 cells. Particularly, we found that MT neurons in old monkeys exhibited enhanced maximum visual responses, higher levels of spontaneous activity and decreased signal-to-noise ratios. In addition, we also found age-related changes in neuronal adaptation to visual motion in MT. Compared with young animals, the contrast gain of MT neurons in old monkeys is less affected, but the response gain by adaptation of MT neurons is more affected. Our results suggest that there may be an anomalous visual processing in both the magnocellular and parvocellular pathways. The neural changes described here are consistent with an age-related degeneration of intracortical inhibition and could underlie some deficits in visual function during normal aging.

Visual function in patients of a polytrauma rehabilitation center: A descriptive study

Little is known about the visual function deficits associated with polytrauma injury. In this retrospective descriptive study, we examined the records of a clinic established to assess visual function in patients experiencing deployment-related polytrauma. We describe the clinical findings and present a vision examination protocol that may be useful for screening polytrauma patients in other settings. Data from our sample suggested that self-reported vision complaints were common (74%) and confirmed that visual impairment occurred in 38% of all cases. When examining the mechanism of injury, we found that polytrauma due to blast injuries appeared to more than double the risk of visual impairment compared with all other polytrauma causes (i.e., motor vehicle accidents, gunshot and/or shrapnel, assault, falls, or anoxia). The rate of visual impairment in blast-related injury was 52% compared with 20% for all other sources of injury. Visual complaints and impairments were common in the polytrauma patients studied. This finding suggests that comprehensive eye examinations should be routinely administered, particularly when the mechanism of injury involves a blast.