Central Visual System Research Articles

Peripheral myopic defocus signal affects the efficiency of visual information processing in myopic children.

Spectacle lenses with peripheral lenslets have shown promise for myopia control by providing peripheral myopic defocus signals. Here, we aimed to investigate the impact of prolonged exposure (>6 months) to peripheral myopic defocus on visual information processing in myopic children. The study included 30 myopic children who habitually wore spectacle lenses with highly aspherical lenslets (HAL group) and 34 children who habitually wore single-vision (SV group) spectacles. The quick contrast sensitivity function (qCSF) was used to measure contrast sensitivity (CS) under conditions of no or high noise. Both groups were tested with HAL and SV lenses. The perceptual template model was utilised to fit the contrast sensitivity function (CSF) and determine differences in information processing efficiency through internal additive noise ( ) and perceptual template gain (β). The areas under the log CSF in the SV group were significantly higher than for the HAL group in both zero-noise conditions with the SV test lens (p = 0.03) and high-noise conditions with the HAL test lens (p = 0.02). For 2 cycle per degree (cpd) stimuli, β was significantly higher in the SV group with the HAL test lens than in the HAL group (p = 0.02), while there was a trend towards a significant difference in β for 6 cpd stimuli (p = 0.07). However, there were no significant differences in between the two groups, with or without noise interference. The reduced CS observed in myopic children wearing HAL lenses for 6 months or more may be due to decreased β. This suggests that prolonged use of spectacle lenses with peripheral myopic defocus signals may compromise the central visual system's ability to process additional external noise, resulting in decreased efficiency in visual information processing.

Retinoid therapy restores eye-specific cortical responses in adult mice with retinal degeneration

Despite the recent emergence of multiple cellular and molecular strategies to restore vision in retinal disorders, it remains unclear to what extent central visual circuits can recover when retinal defects are corrected in adulthood. We addressed this question in an Lrat-/- mouse model of Leber congenital amaurosis (LCA) in which retinal light sensitivity and optomotor responses are partially restored by 9-cis-retinyl acetate administration in adulthood. Following treatment, two-photon calcium imaging revealed increases in the number and response amplitude of visually responsive neurons in the primary visual cortex (V1). In particular, retinoid treatment enhanced responses from the ipsilateral eye, restoring the normal balance of eye-specific responses in V1. Additionally, the treatment rescued the modulation of cortical responses by arousal. These findings illustrate the significant plasticity of the adult central visual system and underscore the therapeutic potential of retinoid administration for adults with retinal diseases.

New Evidence of Central Nervous System Damage in Diabetes: Impairment of Fine Visual Discrimination.

Diabetes can damage both the peripheral sensory organs, causing retinopathy, and the central visual system, leading to contrast sensitivity and impaired color vision in patients without retinopathy. Orientation discrimination is important for shape recognition by the visual system. Our psychophysical findings in this study show diminished orientation discrimination in patients with diabetes without retinopathy. To reveal the underlying mechanism, we established a diabetic mouse model and recorded in vivo electrophysiological data in the dorsal lateral geniculate nucleus (dLGN) and primary visual cortex (V1). Reduced orientation selectivity was observed in both individual and populations of neurons in V1 and dLGN, which increased in severity with disease duration. This diabetes-associated neuronal dysfunction appeared earlier in the V1 than dLGN. Additionally, neuronal activity and signal-to-noise ratio are reduced in V1 neurons of diabetic mice, leading to a decreased capacity for information processing by V1 neurons. Notably, the V1 in diabetic mice exhibits reduced excitatory neuronal activity and lower levels of phosphorylated mammalian target of rapamycin (mTOR). Our findings show that altered responses of both populations of and single V1 neurons may impair fine vision, thus expanding our understanding of the underlying causes of diabetes-related impairment of the central nervous system.

NanoDam identifies Homeobrain (ARX) and Scarecrow (NKX2.1) as conserved temporal factors in the Drosophila central brain and visual system.

Temporal patterning of neural progenitors is an evolutionarily conserved strategy for generating neuronal diversity. Type II neural stem cells in the Drosophila central brain produce transit-amplifying intermediate neural progenitors (INPs) that exhibit temporal patterning. However, the known temporal factors cannot account for the neuronal diversity in the adult brain. To search for missing factors, we developed NanoDam, which enables rapid genome-wide profiling of endogenously tagged proteins invivo with a single genetic cross. Mapping the targets of known temporal transcription factors with NanoDam revealed that Homeobrain and Scarecrow (ARX and NKX2.1 orthologs) are also temporal factors. We show that Homeobrain and Scarecrow define middle-aged and late INP temporal windows and play a role in cellular longevity. Strikingly, Homeobrain and Scarecrow have conserved functions as temporal factors in the developing visual system. NanoDam enables rapid cell-type-specific genome-wide profiling with temporal resolution and is easily adapted for use in higher organisms.

Traumatic brain injury to primary visual cortex produces long-lasting circuit dysfunction

Primary sensory areas of the mammalian neocortex have a remarkable degree of plasticity, allowing neural circuits to adapt to dynamic environments. However, little is known about the effects of traumatic brain injury on visual circuit function. Here we used anatomy and in vivo electrophysiological recordings in adult mice to quantify neuron responses to visual stimuli two weeks and three months after mild controlled cortical impact injury to primary visual cortex (V1). We found that, although V1 remained largely intact in brain-injured mice, there was ~35% reduction in the number of neurons that affected inhibitory cells more broadly than excitatory neurons. V1 neurons showed dramatically reduced activity, impaired responses to visual stimuli and weaker size selectivity and orientation tuning in vivo. Our results show a single, mild contusion injury produces profound and long-lasting impairments in the way V1 neurons encode visual input. These findings provide initial insight into cortical circuit dysfunction following central visual system neurotrauma.

Gene therapy with caspase-3 small interfering RNA-nanoparticles is neuroprotective after optic nerve damage.

Apoptosis, a key mechanism of programmed cell death, is triggered by caspase-3 protein and lowering its levels with gene therapy may rescue cell death after central nervous system damage. We developed a novel, non-viral gene therapy to block caspase-3 gene expression using small interfering RNA (siRNA) delivered by polybutylcyanoacrylate nanoparticles (CaspNPs). In vitro CaspNPs significantly blocked caspase-3 protein expression in C6 cells, and when injected intraocularly in vivo, CaspNPs lowered retinal capsase-3 immunofluorescence by 57.9% in rats with optic nerve crush. Longitudinal, repeated retinal ganglion cell counts using confocal neuroimaging showed that post-traumatic cell loss after intraocular CaspNPs injection was only 36.1% versus 63.4% in lesioned controls. Because non-viral gene therapy with siRNA-nanoparticles can selectively silence caspace-3 gene expression and block apoptosis in post-mitotic neurons, siRNA delivery with nanoparticles may be promising for neuroprotection or restoration of central visual system damage and other neurological disorders. The animal study procedures were approved by the German National Act on the use of experimental animals (Ethic Committee Referat Verbraucherschutz, Veterinärangelegenheiten; Landesverwaltungsamt Sachsen-Anhalt, Halle, Germany, # IMP/G/01-1150/12 and # IMP/G/01-1469/17).

Outsourcing a visual neuropil – The central visual system of the median eyes of Galeodes granti Pocock, 1903 (Arachnida: Solifugae)

Only a few studies have examined the central visual system of Solifugae until now. To get new insights suitable for phylogenetic analysis we studied the R-cell (or retinula cell) projections and visual neuropils of Galeodes granti using various methods.G. granti possesses large median eyes and rudimentary lateral eyes. In this study, only the R-cells and neuropils of the median eyes were successfully stained. The R-cells terminate in two distinct visual neuropils. The first neuropil is located externally to the protocerebrum directly below the retina, the second neuropil lies in the cell body rind of the protocerebrum, and immediately adjacent is the arcuate body.This layout of the median eye visual system differs from Arachnopulmonata (Scorpiones + Tetrapulmonata). However, there are several similarities with Opiliones. In both, (1) the R-cells are connected to a first and second visual neuropil and not to any other region of the brain, (2) the first neuropil is not embedded in the cell body rind of the protocerebrum, it is rather external to the protocerebrum, (3) the second visual neuropil is embedded in the cell body rind, and (4) the second neuropil abuts the arcuate body. These findings may provide important new characters for the discussion on arachnid phylogeny.

Modification of Peak Plasticity Induced by Brief Dark Exposure.

The capacity for neural plasticity in the mammalian central visual system adheres to a temporal profile in which plasticity peaks early in postnatal development and then declines to reach enduring negligible levels. Early studies to delineate the critical period in cats employed a fixed duration of monocular deprivation to measure the extent of ocular dominance changes induced at different ages. The largest deprivation effects were observed at about 4 weeks postnatal, with a steady decline in plasticity thereafter so that by about 16 weeks only small changes were measured. The capacity for plasticity is regulated by a changing landscape of molecules in the visual system across the lifespan. Studies in rodents and cats have demonstrated that the critical period can be altered by environmental or pharmacological manipulations that enhance plasticity at ages when it would normally be low. Immersion in complete darkness for long durations (dark rearing) has long been known to alter plasticity capacity by modifying plasticity-related molecules and slowing progress of the critical period. In this study, we investigated the possibility that brief darkness (dark exposure) imposed just prior to the critical period peak can enhance the level of plasticity beyond that observed naturally. We examined the level of plasticity by measuring two sensitive markers of monocular deprivation, namely, soma size of neurons and neurofilament labeling within the dorsal lateral geniculate nucleus. Significantly larger modification of soma size, but not neurofilament labeling, was observed at the critical period peak when dark exposure preceded monocular deprivation. This indicated that the natural plasticity ceiling is modifiable and also that brief darkness does not simply slow progress of the critical period. As an antecedent to traditional amblyopia treatment, darkness may increase treatment efficacy even at ages when plasticity is at its highest.

The visual system of Thelyphonida (whip scorpions): Support for Arachnopulmonata

Only a few studies have examined the central visual system of Thelyphonida (whip scorpions) until now. To obtain new insights suitable for phylogenetic analysis we studied the axonal trajectories and neuropil architecture of the central visual systems of two whip scorpion species (Mastigoproctus giganteus and Typopeltis dalyi) with different neuroanatomical techniques (Cobalt fills, Wigglesworth stains, and μCT).The central visual system of whip scorpion comprises one pair of median eyes and one pair of lateral eye triplets. The R-cells (or retinula cells) of both eye types each terminate in a first and a second visual neuropil. Furthermore, a few R-cell fibres from the median eyes leave the second median eye visual neuropil and terminate in the second and the first lateral eye neuropil. This means R-cell terminals from the lateral eyes and the median eyes overlap here. Additionally, the arcuate body and mushroom bodies are described.A detailed comparison of our findings with previously studied chelicerate central visual systems seems to support a monophyly of Arachnopulmonata, i.e. a clade comprising Tetrapulmonata (Thelyphonida, Schizomida, Amblypygi, and Araneae) and Scorpions. Furthermore, the architecture of the central visual systems hints at a close evolutionary relationship of Arachnopulmonata and Xiphosura.

Aging Potentiates Lateral but Not Local Inhibition of Orientation Processing in Primary Visual Cortex.

Aging-related declines in vision can decrease well-being of the elderly. Concerning early sensory changes as in the primary visual cortex, physiological and behavioral reports seem contradictory. Neurophysiological studies on orientation tuning properties suggested that neuronal changes might come from decreased cortical local inhibition. However, behavioral results either showed no clear deficits in orientation processing in older adults, or proposed stronger surround suppression. Through psychophysical experiments and computational modeling, we resolved these discrepancies by suggesting that lateral inhibition increased in older adults while neuronal orientation tuning widths, related to local inhibition, stayed globally intact across age. We confirmed this later result by re-analyzing published neurophysiological data, which showed no systematic tuning width changes, but instead displayed a higher neuronal noise with aging. These results suggest a stronger lateral inhibition and mixed effects on local inhibition during aging, revealing a more complex picture of age-related effects in the central visual system than people previously thought.

Contrast Sensitivity Abnormalities in Deaf Individuals.

Purpose:Hearing impaired children are heavily dependent on their sense of vision to develop efficient communication skills; any contrast sensitivity defect can negatively impact their lives because they are not able to use auditory stimuli to recognize probable dangers in the world around them. The purpose of this study was to determine the contrast sensitivity abnormalities in deaf individuals.Methods:In this cross-sectional study, contrast sensitivity of 15- to 20-year-old high-school boys with hearing disability from Tehran, Iran were evaluated. Sixty-four eyes were tested for contrast sensitivity and refractive error. All subjects had an intelligence quotient (IQ) >70. We investigated their contrast sensitivity with Vector vision CVS-1000 in 4 different spatial frequencies.Results:Profound hearing loss was noted in 50% of the subjects. The frequency of contrast sensitivity abnormalities in 4 different spatial frequencies varied between 51.6% and 65.6%. The largest abnormalities were recorded at 18 cycles per degree. Only 12.5% of deaf students had corrected distance visual acuity (CDVA) greater than zero (in LogMAR). The abnormalities in contrast sensitivity showed no correlation with the type or severity of hearing loss.Conclusion:Hearing impaired boys are at a greater risk for contrast sensitivity abnormalities than boys with normal hearing. The larger frequency of contrast sensitivity abnormalities in high spatial frequencies than in other frequencies may demonstrate greater defects in the central visual system compared with the periphery in individuals with hearing loss.

Elevated Intraocular Pressure Induces Amyloid-β Deposition and Tauopathy in the Lateral Geniculate Nucleus in a Monkey Model of Glaucoma.

Recent evidence has suggested a potential association between Alzheimer's disease (AD) and glaucoma and found significant deposition of amyloid-β (Aβ) and Tau protein in the retinas of glaucoma patients. However, no coherent finding has emerged regarding the AD-like changes in the central visual system (CVS). Studies confirming the presence of Aβ and Tau neuropathology are warranted to identify the underlying mechanism that contributes to the visual impairment observed in glaucoma. A chronic glaucoma model was established in rhesus monkeys. The retina, optic nerve, CVS including the lateral geniculate nucleus (LGN) and primary visual cortex (V1), and cognitive areas including the hippocampus (Hpp) were evaluated. Aβ 1-42 and phosphorylated-Tau (p-Tau) were tested in the aforementioned structure using immunohistochemistry, Western blotting and ELISA, and the neuritic plaques and argyrophilic structures/neurofilaments were observed using silver staining and transmission electron microscopy (TEM). Immunohistochemistry revealed positive Aβ and p-Tau labeling in the LGN. According to Western blotting assay and ELISA, Aβ and p-Tau were present in the LGN. Aβ also was expressed weakly in the primary visual cortex. In contrast, the hippocampus, which is the most severely affected region in AD, showed no positive labeling. Structurally, silver staining and TEM revealed neuritic plaques and argyrophilic structures/neurofibrillary tangles, in the LGN. For the first time to our knowledge, these data collectively establish the existence of hallmark AD-like pathologies in the glaucomatous LGN. Our results may provide new targets for developing research therapies that will enhance neuroprotection in glaucoma patients.

In Ovo Electroporation Methods in Chick Embryos.

To elucidate a gene function, in vivo analysis is indispensable. We can carry out gain and loss of function experiment of a gene of interest by electroporation in ovo and ex ovo culture system on early-stage and advanced-stage chick embryos, respectively. In this section, we introduce in/ex ovo electroporation methods for the development of the chick central nervous system and visual system investigation.

A framework to explore the visual brain in glaucoma with lessons from models and man

Vision loss in glaucoma is associated with death of retinal ganglion cells. High intraocular pressure is a major risk factor for vision loss from glaucoma, and lowering eye pressure is the goal of all available medical and surgical treatments. Taking a bold step forward, the restoration of vision after severe glaucoma damage is a new Audacious Goal established by National Eye Institute (Sieving, 2012). This means that retinal ganglion cell repair, and replacement, must be considered in the context of visual function restoration. To restore visual function, retinal ganglion cells, after long-distance axonal growth and guidance, should connect to specific target neurons in subcortical visual structures. At the time of the establishment of these connections, the fate of target cells is critical along with the health of retinal ganglion cells. In fact, several lines of evidence demonstrate glaucomatous neural degeneration occurs throughout the central visual system where most information processing takes place. Evidence from multiple studies in experimental glaucoma models, human autopsy cases and neuroimaging studies point to the degeneration of neurons in the lateral geniculate nucleus, a subcortical hub of functional connectivity between the eye and the visual cortex. Maintaining and re-establishing connections of retinal ganglion cells to target neurons in major visual structures is a key endpoint for regenerative medicine strategies. This paper critically reviews studies of visual brain changes in man and experimental animal models, and discusses key factors in the experimental design that are relevant to restoring vision loss in human disease.

V10. Learning to comprehend time-compressed speech affects premotor and cerebellar regions in late-blind and normally sighted subjects

Individuals suffering from vision loss of a peripheral origin may learn to understand spoken language at a rate of up to about 22 syllables per second (syl/s), exceeding by far the maximum performance level of untrained listeners (ca. 8 syl/s). Previous findings (Dietrich et al., 2013, BMC Neuroscience) indicate that, in addition to the classical language zones (left inferior frontal gyrus, bilateral middle temporal gyrus), right visual cortex (V1), left supplementary motor area (SMA), and cerebellum contribute to the processing of accelerated speech in blind subjects. As an extension, the present training experiment using functional magnetic resonance imaging (fMRI) addresses the issue whether acquisition of ultra-fast (18 syl/s) speech perception skills induces central-visual hemodynamic activation in late-blind participants. Furthermore, we asked to what extent subjects with normal or residual vision can improve understanding of accelerated verbal utterances and whether differential training effects for sighted as compared to blind subjects can be demonstrated. To these ends, prior to and after a training period of ca. six months, fMRI was performed while subjects were listening to forward and time-reversed sentence utterances of a moderately fast (8 syl/s) or an ultra-fast syllable rate (18 syl/s). Eight participants, varying in the amount of residual visual functions, considerably improved their comprehension of ultra fast speech comprehension (pre-training: 9%, SD=13.4, post-training: 70%, SD=16.9; correct words in a sentence repetition task). Among other regions, left SMA, bilateral cerebellum, and right V1 showed a significant interaction (ANOVA) of the factors rate (8 vs. 18 syl/s) and stage (untrained vs. trained). After training, during the ultra-fast speech condition all subjects displayed an increase of hemodynamic activation in left SMA, and cerebellar activation was increased in five of eight participants. Training-induced hemodynamic activation of the central-visual system was only found in subjects with very low visual acuity. Thus, perceptual learning seems to involve SMA-cerebellar circuits, primarily known from motor learning tasks. It can be assumed that SMA and cerebellum contribute to a mechanism of time-critical processing that is required for the reconstruction of the syllabic structure ultra-fast speech during lexical encoding toward verbal working memory. Furthermore, in spite of similar behavioral performance, trained experts appear to use distinct strategies of ultra-fast speech processing depending on whether the occipital cortex is still deployed for visual processing (Fig. 1).

Experience-related structural changes of degenerated occipital white matter in late-blind humans - a diffusion tensor imaging study.

Late-blind humans can learn to understand speech at ultra-fast syllable rates (ca. 20 syllables/s), a capability associated with hemodynamic activation of the central-visual system. Thus, the observed functional cross-modal recruitment of occipital cortex might facilitate ultra-fast speech processing in these individuals. To further elucidate the structural prerequisites of this skill, diffusion tensor imaging (DTI) was conducted in late-blind subjects differing in their capability of understanding ultra-fast speech. Fractional anisotropy (FA) was determined as a quantitative measure of the directionality of water diffusion, indicating fiber tract characteristics that might be influenced by blindness as well as the acquired perceptual skills. Analysis of the diffusion images revealed reduced FA in late-blind individuals relative to sighted controls at the level of the optic radiations at either side and the right-hemisphere dorsal thalamus (pulvinar). Moreover, late-blind subjects showed significant positive correlations between FA and the capacity of ultra-fast speech comprehension within right-hemisphere optic radiation and thalamus. Thus, experience-related structural alterations occurred in late-blind individuals within visual pathways that, presumably, are linked to higher order frontal language areas.

Chapter 18 - Retinal and visual system: occupational and environmental toxicology

Occupational chemical exposure often results in sensory systems alterations that occur without other clinical signs or symptoms. Approximately 3000 chemicals are toxic to the retina and central visual system. Their dysfunction can have immediate, long-term, and delayed effects on mental health, physical health, and performance and lead to increased occupational injuries. The aims of this chapter are fourfold. First, provide references on retinal/visual system structure, function, and assessment techniques. Second, discuss the retinal features that make it especially vulnerable to toxic chemicals. Third, review the clinical and corresponding experimental data regarding retinal/visual system deficits produced by occupational toxicants: organic solvents (carbon disulfide, trichloroethylene, tetrachloroethylene, styrene, toluene, and mixtures) and metals (inorganic lead, methyl mercury, and mercury vapor). Fourth, discuss occupational and environmental toxicants as risk factors for late-onset retinal diseases and degeneration. Overall, the toxicants altered color vision, rod- and/or cone-mediated electroretinograms, visual fields, spatial contrast sensitivity, and/or retinal thickness. The findings elucidate the importance of conducting multimodal noninvasive clinical, electrophysiologic, imaging and vision testing to monitor toxicant-exposed workers for possible retinal/visual system alterations. Finally, since the retina is a window into the brain, an increased awareness and understanding of retinal/visual system dysfunction should provide additional insight into acquired neurodegenerative disorders.

Morphologic changes in the anterior and posterior subregions of V1 and V2 and the V5/MT+ in patients with primary open-angle glaucoma

The aim of this study was to investigate possible morphologic changes of the visual cortex in primary open-angle glaucoma (POAG) with varying severity. Twenty normal controls (NC), 19 mild (MP) and 17 severe (SP) POAG patients were recruited and scanned using magnetic resonance imaging. Multi-parameter morphologic analyses with regions of interest (V5/MT+, anterior and posterior subregions of V1 and V2) were used to assess the cortical changes among the three groups. Compared with the NC group, decreased cortical thickness was detected in the V5/MT+ area in the MP group and in all of the investigated visual areas except the posterior subregion of V1 in the SP group. Unexpectedly, cortical thinning of the posterior subregion of V2 was detected in the SP group compared with the NC and MP groups. For the other morphologic parameters, only gray matter volume in the posterior subregion of V2 and mean curvature in the V5/MT+ were significantly changed in the SP group. In addition, the clinical measurements were positively correlated with the cortical thickness of the V5/MT+ and the posterior subregion of V2. In conclusion, the V5/MT+ area is involved in early disruption of POAG and the cortical degeneration may be progressive and heterogeneous in different visual cortices. Early neuroprotective therapies on the retina and central visual system may help to preserve vision in patients with POAG.

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.

Merging Psychophysical and Psychometric Theory to Estimate Global Visual State Measures from Forced-Choices

Visual acuity, a forced-choice psychophysical measure of visual spatial resolution, is the sine qua non of clinical visual impairment testing in ophthalmology and optometry patients with visual system disorders ranging from refractive error to retinal, optic nerve, or central visual system pathology. Visual acuity measures are standardized against a norm, but it is well known that visual acuity depends on a variety of stimulus parameters, including contrast and exposure duration. This paper asks if it is possible to estimate a single global visual state measure from visual acuity measures as a function of stimulus parameters that can represent the patient's overall visual health state with a single variable. Psychophysical theory (at the sensory level) and psychometric theory (at the decision level) are merged to identify the conditions that must be satisfied to derive a global visual state measure from parameterised visual acuity measures. A global visual state measurement model is developed and tested with forced-choice visual acuity measures from 116 subjects with no visual impairments and 560 subjects with uncorrected refractive error. The results are in agreement with the expectations of the model.