Contrast Sensitivity Deficits Research Articles

Active training for amblyopia in adult rodents.

Amblyopia is the most diffused form of visual function impairment affecting one eye, with a prevalence of 1–5% in the total world population. Amblyopia is usually caused by an early functional imbalance between the two eyes, deriving from anisometropia, strabismus, or congenital cataract, leading to severe deficits in visual acuity, contrast sensitivity and stereopsis. While amblyopia can be efficiently treated in children, it becomes irreversible in adults, as a result of a dramatic decline in visual cortex plasticity which occurs at the end of the critical period (CP) in the primary visual cortex. Notwithstanding this widely accepted dogma, recent evidence in animal models and in human patients have started to challenge this view, revealing a previously unsuspected possibility to enhance plasticity in the adult visual system and to achieve substantial visual function recovery. Among the new proposed intervention strategies, non invasive procedures based on environmental enrichment, physical exercise or visual perceptual learning (vPL) appear particularly promising in terms of future applicability in the clinical setting. In this survey, we will review recent literature concerning the application of these behavioral intervention strategies to the treatment of amblyopia, with a focus on possible underlying molecular and cellular mechanisms.

The effect of pharmacological intervention on contrast sensitivity deficits in phenylketonuria

The effect of pharmacological intervention on contrast sensitivity deficits in phenylketonuria

Donepezil increases contrast sensitivity for the detection of objects in scenes

We assessed the effects of donepezil, a drug that stimulates cholinergic transmission, and scopolamine, an antagonist of cholinergic transmission, on contrast sensitivity. 30 young male participants were tested under three treatment conditions: placebo, donepezil, and scopolamine in a random order. Pairs of photographs varying in contrast were displayed left and right of fixation for 50ms. Participants were asked to locate the scene containing an animal. Accuracy was better under donepezil than under scopolamine, particularly for signals of high intensity (at higher levels of contrast). A control experiment showed that the lower performance under scopolamine did not result from the mydriasis induced by scopolamine. The results suggest that cholinergic stimulation, through donepezil, facilitates signal detection in agreement with studies on animals showing that the pharmacological activation of cholinergic receptors controls the gain in the relationship between the stimulus contrast (intensity of the visual input) and visual response. As Alzheimer disease is associated to depletion in acetylcholine, and there is evidence of deficits in contrast sensitivity in Alzheimer, it might be interesting to integrate such rapid and sensitive visual tasks in the biomarkers at early stage of drug development.

On the use of cues to assess attention in dyslexia.

On the use of cues to assess attention in dyslexia.

Treatment of amblyopia in the adult: insights from a new rodent model of visual perceptual learning.

Amblyopia is the most common form of impairment of visual function affecting one eye, with a prevalence of about 1–5% of the total world population. Amblyopia usually derives from conditions of early functional imbalance between the two eyes, owing to anisometropia, strabismus, or congenital cataract, and results in a pronounced reduction of visual acuity and severe deficits in contrast sensitivity and stereopsis. It is widely accepted that, due to a lack of sufficient plasticity in the adult brain, amblyopia becomes untreatable after the closure of the critical period in the primary visual cortex. However, recent results obtained both in animal models and in clinical trials have challenged this view, unmasking a previously unsuspected potential for promoting recovery even in adulthood. In this context, non invasive procedures based on visual perceptual learning, i.e., the improvement in visual performance on a variety of simple visual tasks following practice, emerge as particularly promising to rescue discrimination abilities in adult amblyopic subjects. This review will survey recent work regarding the impact of visual perceptual learning on amblyopia, with a special focus on a new experimental model of perceptual learning in the amblyopic rat.

Assessment of the visual status of older adults on an orthopedic unit.

PURPOSE. To examine the visual status of a cohort of older adults on an orthopedic unit to determine their level of available vision to complete everyday activities in the hospital setting. METHOD. A convenience sample of 50 people was recruited. A visual history was obtained, and participants' glasses were inspected. Distance acuity, reading acuity, and contrast sensitivity were assessed using standardized screening charts. RESULTS. Of participants, 26% did not have their glasses with them until prompted, and 85% had glasses in poor condition. When tested wearing their habitual correction, 6% had low vision, 2% were blind, 41% had reading acuities worse than 20/25, and 28% had contrast sensitivity deficits. CONCLUSION. Visual impairment is prevalent in older adults, yet visual function is not routinely screened in hospitals. Occupational therapists should routinely inquire about patients' visual status, inspect their glasses, and encourage regular eye examinations. Failure to address vision could lead to inaccurate evaluation results.

Changes of spatial and temporal frequency tuning properties of neurons in the middle temporal area of aged rhesus monkeys

Aged humans exhibit severe deficits in visual motion perception and contrast sensitivity under various levels of spatial and temporal modulation. Previous studies indicated that many of these deficits are probably mediated by the neural degradation of the central visual system. To clarify the neuronal response mechanisms underlying the visual degradation during aging, we examined the spatial and temporal frequency tuning properties of neurons from anesthetised and paralysed aged monkeys at the middle temporal area (area MT), which is downstream of the primary visual cortex in the visual processing pathway and thought to be critical for motion perception. We found that the preferred spatial and temporal frequencies, spatial resolution and high temporal frequency cutoff of area MT neurons were reduced in aged monkeys, and were accompanied by the broadened tuning width of spatial frequency, elevated spontaneous activity, and decreased signal-to-noise ratio. These results showed that, for neurons in area MT, aging significantly changed both the spatial and temporal frequency response tuning properties. Such evidence provides new insight into the changes occurring at the electrophysiological level that may be related to the aging-related visual deficits, especially in processing spatial and temporal information.

A role for melanopsin in alpha retinal ganglion cells and contrast detection.

Distinct subclasses of retinal ganglion cells (RGCs) mediate vision and nonimage-forming functions such as circadian photoentrainment. This distinction stems from studies that ablated melanopsin-expressing intrinsically photosensitive RGCs (ipRGCs) and showed deficits in nonimage-forming behaviors, but not image vision. However, we show that the ON alpha RGC, a conventional RGC type, is intrinsically photosensitive in mammals. In addition to their classical response to fast changes in contrast through rod/cone signaling, melanopsin expression allows ON alpha RGCs to signal prior light exposure and environmental luminance over long periods of time. Consistent with the high contrast sensitivity of ON alpha RGCs, mice lacking either melanopsin or ON alpha RGCs have behavioral deficits in contrast sensitivity. These findings indicate a surprising role for melanopsin and ipRGCs in vision.

Circadian Perinatal Photoperiod Has Enduring Effects on Retinal Dopamine and Visual Function

Visual system development depends on neural activity, driven by intrinsic and light-sensitive mechanisms. Here, we examined the effects on retinal function due to exposure to summer- and winter-like circadian light cycles during development and adulthood. Retinal light responses, visual behaviors, dopamine content, retinal morphology, and gene expression were assessed in mice reared in seasonal photoperiods consisting of light/dark cycles of 8:16, 16:8, and 12:12 h, respectively. Mice exposed to short, winter-like, light cycles showed enduring deficits in photopic retinal light responses and visual contrast sensitivity, but only transient changes were observed for scotopic measures. Dopamine levels were significantly lower in short photoperiod mice, and dopaminergic agonist treatment rescued the photopic light response deficits. Tyrosine hydroxylase and Early Growth Response factor-1 mRNA expression were reduced in short photoperiod retinas. Therefore, seasonal light cycles experienced during retinal development and maturation have lasting influence on retinal and visual function, likely through developmental programming of retinal dopamine.

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.

Influence of multiple sclerosis, age and degree of disability, in the position of the contrast sensitivity curve peak

Context:Contrast sensitivity (CS) function is one of the most important tests available for evaluating visual impairment. Multiple sclerosis (MS) can produce highly selective losses in visual function and psychophysical studies have demonstrated CS deficits for some spatial frequencies.Aims:This work studies the differences in CS between a group of controls and a group of MS patients, focusing on the location of the maximum sensitivity peak, shape of the curve, and determination of the most affected spatial frequencies.Materials and Methods:Using a sinusoidal stimulus the authors assessed CS function in 28 subjects with definitive relapsing remitting MS, and in 50 controls with acuities of 20/25 or better. The peaks of the CS curves were studied by fitting third degree polynomials to individual sets of data.Results:Compared with the control group, the CS function curve for MS subjects showed more deficits in extreme points (low- and high-spatial frequencies). Our results display significant CS losses, at the high-frequencies band level, in the beginning of the disease. When the disease progresses and the disabilities appear, there are greater losses at the low-frequencies band level. In average, the CS curve peaks for the MS group were shifted in relation to the control group.Conclusions:CS losses in the MS group suggest an association with ageing and disability level in the expanded disability status scale. The position of the CS function peak is influenced by MS, age, and degree of disability.

Visual Contrast Sensitivity Deficits in ‘Normal' Visual Field of Patients with Homonymous Visual Field Defects due to Stroke: A Pilot Study

Background: Homonymous visual field defects (VFD) are common following stroke, and often recover, partially or fully, by unknown mechanisms. In clinical practice, visual field recovered on perimetry is often considered perceptually normal. However, studies have shown contrast sensitivity (CS) deficits in patients with stroke and homonymous VFD. This study investigated the origin of visual CS loss in patients with VFD due to stroke. We hypothesised that CS deficits would be found in visual field areas appearing normal on perimetry, in patients with ischaemic stroke affecting the retrochiasmal visual system, and that the spatiotemporal properties of this CS loss would be consistent with those of ‘blindsight', perhaps suggesting similar underlying mechanisms. Methods: CS measurements were made in 20 healthy participants, and in 7 patients with stroke causing homonymous VFD sparing foveal vision, measured using Humphrey static perimetry (SITA-Fast 24-2 procedure). Importantly, patients with concomitant visuospatial neglect were excluded. CS measurements were made using a modification of the method of increasing contrast, corrected for reaction time. Three spatial stimuli were used, at several spatial frequencies: (1) large sinusoidal gratings; (2) foveal Gabor patches; and (3) Gabor patches presenting in the putatively recovered visual field, near VFD. Stimuli with different temporal profiles were used to selectively stimulate transient and sustained visual channels, to provide insight into mechanisms of visual loss and/or recovery. Analysis of variance (ANOVA) was used in the analysis of the measurements, allowing for correction for age and stimulus eccentricity. Results: ANOVA for sustained grating stimuli showed orientation-selective (horizontal) CS loss (p = 0.025); no such loss was apparent in the central visual field (foveal Gabor stimuli). Localised CS close to VFD was reduced in stroke-affected hemifields compared with unaffected hemifields (p ≤ 0.005), though these areas appeared normal on perimetry. In these areas, CS was relatively preserved for transient compared with sustained stimuli (Wilcoxon signed rank tests). Conclusions: The finding of specific CS deficits in the normal-appearing visual field of patients with homonymous VFD due to stroke suggests that static perimetry provides an inadequate assessment of visual function in these patients, with clear implications for testing of vision in clinical practice. The results are consistent with relative sparing of the transient/magnocellular visual channel. These findings demand further investigation. If confirmed in larger, longitudinal studies, this will have important implications for the mechanisms of recovery, and may provide a target for visual rehabilitation - for example, using repeated detection practice (‘perceptual learning').

Developmental dissociation of visual dorsal stream parvo and magnocellular representations and the functional impact of negative retinotopic BOLD responses

Localized neurodevelopmental defects provide an opportunity to study structure–function correlations in the human nervous system. This unique multimodal case report of epileptogenic dysplasia in the visual cortex allowed exploring visual function across distinct pathways in retinotopic regions and the dorsal stream, in relation to fMRI retinotopic mapping and spike triggered BOLD responses.Pre-surgical EEG/video monitoring, MRI/DTI, EEG/fMRI, PET and SPECT were performed to characterize structure/function correlations in this patient with a very early lesion onset. In addition, we included psychophysical methods (assessing parvo/konio and magnocellular pathways) and retinotopic mapping.We could identify dorsal stream impairment (with extended contrast sensitivity deficits within the input magno system contrasting with more confined parvocellular deficits) with disrupted active visual field input representations in regions neighboring the lesion. Simultaneous EEG/fMRI identified perilesional and retinotopic bilaterally symmetric BOLD deactivation triggered by interictal spikes, which matched the contralateral spread of magnocellular dysfunction revealed in the psychophysical tests. Topographic changes in retinotopic organization further suggested long term functional effects of abnormal electrical discharges during brain development.We conclude that fMRI based visual field cortical mapping shows evidence for retinotopic dissociation between magno and parvocellular function well beyond striate cortex, identifiable in high level dorsal visual representations around visual area V3A which is consistent with the effects of epileptic spike triggered negative BOLD.

Correlation of Inner Retinal Thickness Evaluated by Spectral-Domain Optical Coherence Tomography and Contrast Sensitivity in Parkinson disease

To compare inner retinal layer (IRL) thickness measured by spectral-domain optical coherence tomography (SD-OCT) and contrast sensitivity (CS) in patients with Parkinson disease (PD) and in healthy control (HC) subjects. Consecutive patients with and without PD were prospectively analyzed using SD-OCT and Pelli-Robson CS testing. SD-OCT IRL (ganglion-cell complex) thickness, consisting of the nerve fiber layer, ganglion cell layer, and inner plexiform layer, was segmented using an RTVue Model-RT100 with an EMM5 scan parameter covering a 5.0 × 5.0 mm cube centered on the fovea. Thickness voxel measurements at 0.25-mm intervals at sequential radial distances from the foveola were acquired horizontally and vertically. SD-OCT thickness raw data files were imported and analyzed within MATLAB (version 7.10.0). A database of CS scores and IRL thickness values by foveal location was constructed and statistically evaluated using JMP 10 (SAS Institute, Inc, Cary, NC). The results were compared between 28 eyes of 14 patients with PD and 28 eyes of 14 HC subjects. Controlling for age, mean CS scores of monocular right and randomized eyes were statistically lower in PD eyes (P < 0.05). IRL was significantly thinner in PD eyes than in HC eyes at several distances from the foveola (P < 0.05). The most numerous and significant thickness differences by diagnosis were located in the superior quadrant at a distance of 1.00-1.75 mm from the foveal center (17 μm; P < 0.01, maximum significant thickness difference and P value). Correlation was demonstrated between monocular CS and IRL thickness by diagnosis at multiple foveal locations for HC eyes as follows: nasal quadrant, 0.75-1.00 mm (P < 0.02); temporal quadrant, 0.50-1.00 mm (P < 0.05); superior quadrant, 1.00 mm (P < 0.05); and inferior quadrant, 1.00 mm (P < 0.03). No significant correlation was found between monocular CS and IRL thickness within PD subjects (P > 0.05 for each foveal location measured). CS and foveal IRL thickness are decreased in patients with PD. CS and IRL thickness correlated in HC subjects; however, no such correlation was demonstrated in PD. The functional deficit of dopaminergic interneurons, including amacrine cells, may outstrip the anatomic structural changes in the inner retina of PD patients. Inner retinal atrophic changes may underlie the pathogenesis of CS deficit and IRL thinning in PD.

“Sightblind”: Perceptual Deficits in the “Intact” Visual Field

Unilateral visual cortex lesions caused by stroke or trauma lead to blindness in contralateral visual field – a condition called homonymous hemianopia. Although the visual field area processed by the uninjured hemisphere is thought to be “intact,” it also exhibits marked perceptual deficits in contrast sensitivity, processing speed, and contour integration. Such patients are “sightblind” – their blindness reaches far beyond the primary scotoma. Studies showing perceptual deficits in patients’ intact fields are reviewed and implications of these findings are discussed. It is concluded that consequences of partial blindness are greater than previously thought, since perceptual deficits in the “intact” field likely contribute to subjective vision loss in patients with visual field defect. This has important implications for vision diagnosis and rehabilitation.

Visual Acuity, Crowding, and Stereo-Vision Are Linked in Children with and without Amblyopia

During development, the presence of strabismus and anisometropia frequently leads to amblyopia, a visual disorder characterized by interocular acuity differences. Although additional deficits in contrast sensitivity, crowding (the impaired recognition of closely spaced objects), and stereoacuity are common, the relationship between these abilities is unclear. We measured the covariation between these four abilities in children 4 to 9 years of age (n = 72) with strabismus, anisometropia, or mixed strabismus/anisometropia, and unaffected controls. Children reported the orientation of a target (a modified "Pac-Man," similar to Landolt-C stimuli) using four "ghosts" as references. Using a modified staircase procedure we measured threshold size (acuity), contrast detection, foveal crowding (the minimum separation between target and ghost-flankers supporting accurate identification), and stereoacuity (with random-dot stereogram ghosts). Group averages revealed significant interocular differences (IODs) in acuity for all three clinical groups (0.2-0.3 log minutes), and significant crowding IODs for the strabismic and mixed groups (0.6 and 0.4°, respectively). Nonetheless, crowding IODs were correlated with acuity IODs in all four groups (r values between 0.43 and 0.59 and P < 0.05; P = 0.07 in the mixed group). Similarly, the occurrence of stereo-blindness (most common in strabismic and mixed groups) was associated with a significant increase in IODs for both acuity and crowding (each P < 0.05). No correlations were found with contrast detection. Our results demonstrate an association between IODs in acuity and crowding and, furthermore, between these IODs and the presence of stereo-vision. We suggest that the deficits derived from strabismus and anisometropia lay along a continuum with abilities observed during normal development.

Low-level processing deficits underlying poor contrast sensitivity for moving plaids in anisometropic amblyopia

Many studies using random dot kinematograms have indicated a global motion processing deficit originated from extrastriate cortex, specifically middle temporal area (MT) and media superior temporal area (MST), in patients with amblyopia. However, the nature of this deficit remains unclear. To explore whether the ability of motion integration is impaired in amblyopia, contrast sensitivity for moving plaids and their corresponding component gratings were measured over a range of stimulus durations and spatial and temporal frequencies in 10 control subjects and 13 anisometropic amblyopes by using a motion direction discrimination task. The results indicated a significant loss of contrast sensitivity for moving plaids as well as for moving gratings at intermediate and high spatial frequencies in amblyopic eyes (AEs). Additionally, we found that the loss of contrast sensitivity for moving plaids was statistically equivalent to that for moving component gratings in AEs, that is, the former could be almost completely accounted for by the latter. These results suggest that the integration of motion information conveyed by component gratings of moving plaids may be intact in anisometropic amblyopia, and that the apparent deficits in contrast sensitivity for moving plaids in anisometropic amblyopia can be almost completely attributed to those for gratings, that is, low-level processing deficits.

Visual contrast sensitivity in Alzheimer’s disease, mild cognitive impairment, and older adults with cognitive complaints

Deficits in contrast sensitivity (CS) have been reported in Alzheimer’s disease (AD). However, the extent of these deficits in prodromal AD stages, including mild cognitive impairment (MCI) or even earlier, has not been investigated. In this study, CS was assessed using frequency doubling technology in older adults with AD (n = 10), amnestic MCI (n = 28), cognitive complaints without performance deficits (CC; n = 20), and healthy controls (HC; n = 29). The association between CS and cognition was also evaluated. Finally, the accuracy of CS measures for classifying MCI versus HC was evaluated. CS deficits were found in AD and MCI, while CC showed intermediate performance between MCI and HC. Upper right visual field CS showed the most significant difference among groups. CS was also associated with cognitive performance. Finally, CS measures accurately classified MCI versus HC. The CS deficits in AD and MCI, and intermediate performance in CC, indicate that these measures are sensitive to early AD-associated changes. Therefore, frequency doubling technology-based measures of CS may have promise as a novel AD biomarker.

Impaired magnocellular/dorsal stream activation predicts impaired reading ability in schizophrenia.

In healthy humans, passage reading depends upon a critical organizing role played by the magnocellular/dorsal visual pathway. In a recent study, we found a significant correlation between orthographic reading deficits in schizophrenia and deficits in contrast sensitivity to low spatial frequency stimuli, suggesting an underlying magnocellular processing abnormality. The interrelationship between magnocellular dysfunction and passage reading impairments in schizophrenia was investigated in 21 patients with schizophrenia and 17 healthy control volunteers using behavioral and functional MRI (fMRI) based measures. fMRI activation patterns during passage- and single-word reading were evaluated in relation to cortical areas with differential sensitivity to low versus high spatial frequency cortical regions indentified using a phase-encoded fMRI paradigm.On average, patients with schizophrenia read at the 6th grade level, despite completion of more than 12 years of education and estimated normal pre-morbid IQ. Schizophrenia patients also showed significantly impaired contrast sensitivity to low spatial frequencies and abnormal neural activity in response to stimulation with low spatial frequencies, consistent with dysfunction of magnocellular processing. Further, these magnocellular deficits were predictive of poor performance on a standardized psychoeducational test of passage reading. These findings suggest that reading is an important index of cognitive dysfunction in schizophrenia and highlight the contribution of magnocellular dysfunction to overall cognitive impairments in schizophrenia.

Retinal Dopamine Mediates Multiple Dimensions of Light-Adapted Vision

Dopamine is a key neuromodulator in the retina and brain that supports motor, cognitive, and visual function. Here, we developed a mouse model on a C57 background in which expression of the rate-limiting enzyme for dopamine synthesis, tyrosine hydroxylase, is specifically disrupted in the retina. This model enabled assessment of the overall role of retinal dopamine in vision using electrophysiological (electroretinogram), psychophysical (optokinetic tracking), and pharmacological techniques. Significant disruptions were observed in high-resolution, light-adapted vision caused by specific deficits in light responses, contrast sensitivity, acuity, and circadian rhythms in this retinal dopamine-depleted mouse model. These global effects of retinal dopamine on vision are driven by the differential actions of dopamine D1 and D4 receptors on specific retinal functions and appear to be due to the ongoing bioavailability of dopamine rather than developmental effects. Together, our data indicate that dopamine is necessary for the circadian nature of light-adapted vision as well as optimal contrast detection and acuity.