It has often been postulated that asymmetries in performance within the visual field (VF) are not characteristic of early visual processing. Here, human retinal (naso/temporal), cortical (left/right) and superior/inferior patterns of asymmetry were explored with achromatic contrast sensitivity (CS) tasks, that probed distinct spatiotemporal frequency channels. Low spatial, high temporal frequency stimuli (illusory frequency-doubling (FD)) yielded superior and temporal field disadvantage. Independent right and nasal visual hemifield patterns of disadvantage were found when probing an intermediate spatial frequency (ISF) channel, with stationary sinusoidal gratings. These findings show that asymmetries in spatial vision are explained by independent retinal and cortical mechanisms.

Down syndrome (DS) results from the triplication of approximately 300 human chromosome 21 (Hsa21) genes and affects almost all body organs. Children with DS have defects in visual processing that may have a negative impact on their daily life and cognitive development. However, there is little known about the genes and pathogenesis underlying these defects. Here, we show morphometric in vivo data indicating that the neural retina is thicker in DS individuals than in the normal population. A similar thickening specifically affecting the inner part of the retina was also observed in a trisomic model of DS, the Ts65Dn mouse. Increased retinal size and cellularity in this model correlated with abnormal retinal function and resulted from an impaired caspase-9-mediated apoptosis during development. Moreover, we show that mice bearing only one additional copy of Dyrk1a have the same retinal phenotype as Ts65Dn mice and normalization of Dyrk1a gene copy number in Ts65Dn mice completely rescues both, morphological and functional phenotypes. Thus, triplication of Dyrk1a is necessary and sufficient to cause the retinal phenotype described in the trisomic model. Our data demonstrate for the first time the implication of DYRK1A overexpression in a developmental alteration of the central nervous system associated with DS, thereby providing insights into the aetiology of neurosensorial dysfunction in a complex disease.

It is unknown whether independent neural damage may occur in the pre-/absent vascular diabetic retinopathy (DR). To exclude vasculopathy, it is important to measure the integrity of the blood-retinal barrier (BRB). This cross-sectional study addressed this problem in type 1 diabetic patients with normal ocular fundus and absent breakdown of the BRB (confirmed with vitreous fluorometry). These were compared with a group with disrupted BRB (with normal fundus or initial DR) and normal controls. Multifocal electroretinography and chromatic/achromatic contrast sensitivity were measured in these 42 patients with preserved visual acuity. Amplitudes of neurophysiological responses (multifocal electroretinogram) were decreased in all eccentricity rings in both clinical groups, when compared with controls, with sensitivity >78% for a specificity level of 90%. Implicit time changes were also found in the absence of initial DR. Impaired contrast sensitivity along chromatic axes was also observed, and achromatic thresholds were also different between controls and both clinical groups. The pattern of changes in the group without baseline BRB permeability alterations, as probed by psychophysical and electrophysiological measurements, does thereby confirm independent damage mechanisms. We conclude that retinal neuronal changes can be diagnosed in type 1 diabetes, independently of the breakdown of the BRB and onset of vasculopathy.

Psychophysical visual field asymmetries are widely documented and have been attributed to anatomical anisotropies both at the retinal and cortical levels. This debate on whether such differences originate within the retina itself or are due to higher visual processing may be illuminated if concomitant anatomical, physiological, and psychophysical measures are taken in the same individuals. In the current study, we have focused on the study of objective functional and structural asymmetries at the retinal level and examined their putative correlation with visual performance asymmetries. Forty healthy participants (80 eyes; 13 male and 27 female subjects) were included in this study. Objective functional/structural asymmetries were probed using the multifocal electroretinogram (mfERG) technique and optical coherence tomography (OCT), respectively. A nasal/temporal pattern of asymmetry (nasal visual hemifield disadvantage) was found for all methods (retinal thickness, contrast sensitivity, and mfERG P1 amplitude). Furthermore, superior/inferior asymmetries could be documented only with psychophysics and structural measures. These patterns likely arise at different levels of the retina as inferred by partly independent correlation patterns. We conclude that patterns of structural/functional asymmetries arise at different levels of visual processing with a strong retinal contribution.

The influence of normal aging in early, intermediate and high-level visual processing is still poorly understood. We have addressed this important issue in a large cohort of 653 subjects divided into five distinct age groups, [20;30[, [30;40[, [40;50[, [50;60[and [60;[. We applied a broad range of psychophysical tests, testing distinct levels of the visual hierarchy, from local processing to global integration, using simple gratings (spatial contrast sensitivity -CS- using high temporal/low spatial frequency or intermediate spatial frequency static gratings), color CS using Landolt patches, moving dot stimuli (Local Speed Discrimination) and dot patterns defining 3D objects (3D Structure from Motion, 3D SFM). Aging data were fitted with linear or quadratic regression models, using the adjusted coefficient of determination (R2 a) to quantify the effect of aging. A significant effect of age was found on all visual channels tested, except for the red-green chromatic channel. The high temporal low spatial frequency contrast sensitivity channel showed a mean sensitivity loss of 0.75 dB per decade (R2 a = 0.17, p<0.001), while the lower intermediate spatial frequency channel showed a more pronounced decrease, around 2.35 dB (R2 a = 0.55, p<0.001). Concerning low-level motion perception, speed discrimination decreased 2.71°/s (R2 a = 0.18, p<0.001) and 3.15°/s (R2 a = 0.13, p<0.001) only for short presentations for horizontal and oblique meridians, respectively. The 3D SFM task, requiring high-level integration across dorsal and ventral streams, showed the strongest (quadratic) decrease of motion coherence perception with age, especially when the task was temporally constrained (R2 a = 0.54, p<0.001). These findings show that visual channels are influenced by aging into different extent, with time presenting a critical role, and high-level dorso-ventral dominance of deterioration, which accelerates with aging, in contrast to the other channels that show a linear pattern of deterioration.

Visual cortical plasticity induced by overt retinal lesions (scotomas) has remained a controversial phenomenon. Here we studied cortical plasticity in a silent model of retinal ganglion cell loss, documented by in vivo optical biopsy using coherence tomography. The cortical impact of non-scotomatous subtle retinal ganglion cell functional and structural loss was investigated in carriers of the mitochondrial DNA 11778G>A mutation causing Leber's hereditary optic neuropathy. We used magnetic resonance imaging (MRI) to measure cortical thickness and fMRI to define retinotopic cortical visual areas V1, V2 and V3 in silent carriers and matched control groups. Repeated Measures analysis of variance revealed a surprising increase in cortical thickness in the younger carrier group (below 21 years of age). This effect dominated in extrastriate cortex, and notably V2. This form of structural plasticity suggests enhanced plastic developmental mechanisms in extrastriate retinotopic regions close to V1 and not receiving direct retinocortical input.

Leber hereditary optic neuropathy (LHON) is a maternally inherited mitochondrial disorder, which leads to initially silent visual loss due to retinal ganglion cell (RGC) degeneration. We aimed to establish a link between features of retinal progressive impairment and putative cortical changes in a cohort of 15 asymptomatic patients harboring the 11778G>A mutation with preserved visual acuity and normal ocular examination. To study plasticity evoked by clinically silent degeneration of RGC we only studied mutation carriers. We phenotyped pre-clinical silent degeneration from the psychophysical, neurophysiological and structural points of view to understand whether retinal measures could be related to cortical reorganization, using pattern electrophysiology, chromatic contrast sensitivity and high-resolution optical coherence tomography to measure macular, RGC nerve fiber layer as well as inner/outer retinal layer thickness. We then performed correlation analysis of these measures with cortical thickness estimates in functionally mapped retinotopic visual cortex. We found that compensatory cortical plasticity occurring in V2/V3 is predicted by the swelling (indicating deficits of axonal transport and intracellular edema) of the macular RGC axonal layer. Increased cortical thickness (CT) in V2 and V3 was observed in peripheral regions, like visual field loss, in these mutation carriers. CT was a very discriminative measure between carriers and controls, as revealed by ROC analysis. Importantly, the substantial cortical reorganization that occurs in the carrier state can be used to provide statistical discrimination between carriers and controls to a level that is similar to measures of retinal dysfunction. We conclude that peripheral cortical compensatory plasticity in early visual areas V2/V3 may be triggered by pathology in peripheral RGC axons in combination with potential developmental changes.

The relation of development and aging with models of visual anisotropies and their influence on low-level visual processing remain to be established. Our main goal was to explore visual performance asymmetries in development and normal aging using low-level contrast sensitivity behavioral tasks [probing two distinct spatiotemporal frequency channels, (a) intermediate spatial and null temporal frequency (3.5 cycles per degree (cpd) and 0 Hz); and (b) low spatial and high temporal frequency (0.25 cpd undergoing 25 Hz counterphase flicker)]. Different patterns of functional asymmetries were investigated within four (two neurodevelopmental and two adult) age groups (N = 258 participants; 8-65 years). We found a left visual hemifield/right hemisphere advantage for only the intermediate spatial frequency channel that was present early in life and remained stable throughout adulthood. In contrast, inferior/superior visual hemifield asymmetries, with a direct ecological meaning, were found for both spatiotemporal frequency channels. This inferior visual hemifield advantage emerged early in life and persisted throughout aging. These findings show that both right hemispheric and dorsal retinotopic patterns of dominance in low-level vision emerge early in childhood, maintaining during aging.