Exploratory Investigation of Brain MRI Lesions According to Whole Sample and Visual Function Subtyping in Children With Cerebral Visual Impairment

Background: There is limited research on brain lesions in children with cerebral visual impairment (CVI) of heterogeneous etiologies and according to associated subtyping and vision dysfunctions. This study was part of a larger project establishing data-driven subtypes of childhood CVI according to visual dysfunctions. Currently there is no consensus in relation to assessment, diagnosis and classification of CVI and more information about brain lesions may be of potential diagnostic value.Aim: This study aimed to investigate overall patterns of brain lesions and associations with level of visual dysfunction and to compare the patterns between the classification subgroups in children with CVI.Methods: School-aged children with CVI received ophthalmological and neuro-psychological/developmental assessments to establish CVI-related subtyping. Other pediatric information was collected from medical records. MRI scans were coded according to a semi-quantitative template including brain regions (right hemisphere, left hemisphere, visual pathways) and summed for total scores. Non-parametric analyses were conducted.Results: 28 children had clinical brain MRI scans available [44% of total sample, Group A (lower severity of visual dysfunctions) n = 16, Group B (higher severity) n = 12]. Total brain scores ranged between 0 and 18 (Group A mdn = 7, IQR = 0.8–10.0, Group B mdn = 10, IQR = 6.5–11.8) and were widespread across regions. 71 per cent had post-geniculate visual pathway damage. The median total brain and hemisphere scores of Group B were higher than subgroup A but differences did not reach statistical significance. No statistically significant associations were found between brain scores and vision variables (acuity, contrast sensitivity).Conclusion: This study found a spread of lesions across all regions on the brain scans in children with congenital CVI. The majority had damage in the postgeniculate visual pathways and visual cortex region suggesting this is an area of interest and potentially informative for diagnosis. However the subtyping classification did not show differences in number or region of lesions though the trend was higher toward Group B. This study confirms the complex diffuse and variable nature of brain lesions in children with congenital CVI, many of whom have other neurological impairments.

Aging effects on contrast sensitivity in visual pathways: A pilot study on flicker adaptation

Contrast sensitivity is reduced in older adults and is often measured at an overall perceptual level. Recent human psychophysical studies have provided paradigms to measure contrast sensitivity independently in the magnocellular (MC) and parvocellular (PC) visual pathways and have reported desensitization in the MC pathway after flicker adaptation. The current study investigates the influence of aging on contrast sensitivity and on the desensitization effect in the two visual pathways. The steady- and pulsed-pedestal paradigms were used to measure contrast sensitivity under two adaptation conditions in 45 observers. In the non-flicker adaptation condition, observers adapted to a pedestal array of four 1°×1° squares presented with a steady luminance; in the flicker adaptation condition, observers adapted to a square-wave modulated luminance flicker of 7.5 Hz and 50% contrast. Results showed significant age-related contrast sensitivity reductions in the MC and PC pathways, with a significantly larger decrease of contrast sensitivity for individuals older than 50 years of age in the MC pathway but not in the PC pathway. These results are consistent with the hypothesis that sensitivity reduction observed at the overall perceptual level likely comes from both the MC and PC visual pathways, with a more dramatic reduction resulting from the MC pathway for adults >50 years of age. In addition, a similar desensitization effect from flicker adaptation was observed in the MC pathway for all ages, which suggests that aging may not affect the process of visual adaptation to rapid luminance flicker.

Transneuronal Degeneration in the Visual Pathway of Rats following Acute Retinal Ischemia/Reperfusion

The maintenance of visual function not only requires the normal structure and function of neurons but also depends on the effective signal propagation of synapses in visual pathways. Synapses emerge alterations of plasticity in the early stages of neuronal damage and affect signal transmission, which leads to transneuronal degeneration. In the present study, rat model of acute retinal ischemia/reperfusion (RI/R) was established to observe the morphological changes of neuronal soma and synapses in the inner plexiform layer (IPL), outer plexiform layer (OPL), and dorsal lateral geniculate nucleus (dLGN) after retinal injury. We found transneuronal degeneration in the visual pathways following RI/R concretely presented as edema and mitochondrial hyperplasia of neuronal soma in retina, demyelination, and heterotypic protein clusters of axons in LGN. Meanwhile, small immature synapses formed, and there are asynchronous changes between pre- and postsynaptic components in synapses. This evidence demonstrated that transneuronal degeneration exists in RI/R injury, which may be one of the key reasons for the progressive deterioration of visual function after the injury is removed.

Age-related decline in function of ON and OFF visual pathways

PurposeSimple psychophysical paradigm is available as a digital application in iOS devices such as iPad to measure the function of ON and OFF visual pathways. However, an age-matched normative database is not readily available. The purpose of the study is to evaluate the response of ON and OFF visual pathways as a function of age.Methods158 normal healthy adults (84 males and 74 females) whose age ranged 18-80 years participated in the study. None of them had any ocular disease (except cataract of grade II or less) and visual acuity of ≤ 20/25. Monocular testing (only one eye) was performed on the ‘EyeSpeed’ application on an iPad at 40cm distance. The targets ranged between 1 to 3 light or dark squares presented randomly in a noise background and participants responded by indicating the number of squares by touching the screen as fast as possible. The main outcome variables are reaction time, accuracy and performance index (1 / speed * accuracy).ResultsThe median reaction time was shorter (Median (IQR): 1.53s (0.49) [dark] Vs 1.76s (0.58) [light], p < 0.001) and accuracy was higher (97.21% (3.30) [dark] Vs 95.15% (5.10) [light], p < 0.001) for dark targets than the light targets. Performance index and reaction time for both target types significantly correlated with age (ρ = −0.41 to −0.43; p < 0.001).ConclusionsThis normative database will be useful to quantify disease-specific defects. More importantly, the ON pathway function can potentially serve as a surrogate for rod photoreceptor function.

Macular Morpho-Functional and Visual Pathways Functional Assessment in Patients with Spinocerebellar Type 1 Ataxia with or without Neurological Signs

Spinocerebellar ataxia type 1 (SCA-ATXN1) is an autosomal dominant, neurodegenerative disease, caused by CAG repeat expansion in the ataxin-1 gene (ATXN1). In isolated reports of patients with neurological signs [symptomatic patients (SP)], macular abnormalities have been described. However, no reports exist about macular anomalies in SCA1 subjects carrying the ATXN1 mutation without neurological signs [not symptomatic carriers (NSC)]. Therefore, the main aim of our work was to evaluate whether the macular functional and morphological abnormalities could be detectable in SP, genetically confirmed and with neurological signs, as well as in SCA-ATXN1-NSC, harboring pathogenic CAG expansion in ATXN1. In addition, we investigated whether the macular involvement could be associated or not to an impairment of RGCs and of their fibers and of the neural conduction along the visual pathways. Herein, nine SCA-ATXN1 subjects (6 SP and 3 NSC) underwent the following examinations: visual acuity and chromatic test assessments, fundus oculi (FO) examination, macular and peripapillary retinal nerve fiber layer thickness (RNFL-T) analysis by Spectral domain-Optical Coherence Tomography (Sd-OCT) acquisition, multifocal electroretinogram (mfERG), pattern reversal electroretinogram (PERG) and visual evoked potentials (VEP) recordings. In four eyes of two SP, visual acuity reduction and chromatic abnormalities were observed; in three of them FO changes associated with macular thinning and outer retinal defects were also detected. In three NSC eyes, slight FO abnormalities were associated with qualitative macular morphological changes. By contrast, abnormal mfERG responses (exclusively from foveal and parafoveal areas) were detected in all SP and NSC (18 eyes). No abnormalities of PERG values, RNFL-T, and VEP responses were found, but in one SP, presenting abnormal papillo-macular bundle neural conduction. Results from our SCA-ATXN1 cohort suggest that a macular dysfunction, detectable by mfERG recordings, may occur in the overt disorder, and unexpectedly in the stage of the disease in which there is still an absence of neurological signs. In NSC, an exclusive dysfunction of preganglionic macular elements can be observed, and this is associated with both normal RGCs function and neural conduction along the visual pathways.

Modeling the Ventral and Dorsal Cortical Visual Pathways Using Artificial Neural Networks

Although in conventional models of cortical processing, object recognition and spatial properties are processed separately in ventral and dorsal cortical visual pathways respectively, some recent studies have shown that representations associated with both objects' identity (of shape) and space are present in both visual pathways. However, it is still unclear whether the presence of identity and spatial properties in both pathways have functional roles. In our study, we have tried to answer this question through computational modeling. Our simulation results show that both a model ventral and dorsal pathway, separately trained to do object and spatial recognition, respectively, each actively retained information about both identity and space. In addition, we show that these networks retained different amounts and kinds of identity and spatial information. As a result, our modeling suggests that two separate cortical visual pathways for identity and space (1) actively retain information about both identity and space (2) retain information about identity and space differently and (3) that this differently retained information about identity and space in the two pathways may be necessary to accurately and optimally recognize and localize objects. Further, modeling results suggests these findings are robust and do not strongly depend on the specific structures of the neural networks.

Evoked Potentials

Evoked potentials provide a noninvasive, sensitive, and quantitative way to assess the functional integrity of the somatosensory, auditory, and visual pathways. The basic principle of evoked potentials is to apply a stimulus (sensory, auditory, or visual) in a controlled manner to create a volley of depolarization and repolarization. This stimulus volley ascends through the peripheral and central sensory, auditory, or visual pathways and can be recorded as the signals pass underneath recording electrodes. The generated evoked potential waveforms can represent either a traveling wave of depolarization in white matter or a stationary depolarization within gray matter. The use of somatosensory and brainstem auditory evoked potentials for outpatients has decreased in the past decades as the quality and availability of neuroimaging have improved; however, their use has had a resurgence in electrophysiologic monitoring and mapping of surgical cases involving the spine, posterior fossa, and supratentorial lesions, for which they are now a part of the standard of care.

Pre- and Postnatal Damage to the Retro-Geniculate Visual Pathways Cause Retinal Degeneration Predictive for Visual Function

To increase the understanding of the relationship between structure and function in individuals with damage to the brain from different stages of maturation of the visual system, we examined 16 teenagers and young adults. We used diffusion-weighted magnetic resonance imaging (MRI) and fiber tractography of the optic radiation (OR) and optical coherence tomography (OCT) of the peripapillary retinal nerve fiber layer (pRNFL) and the ganglion cell layer + inner plexiform layer (GC+IPL) in the macula. Visual field (VF) function was assessed with the Humphrey Field Analyzer (HFA). Injuries to the immature OR were associated with thinning of the pRNFL and GC+IPL, and corresponding VF defects irrespectively of timing of the lesion. However, in cases with bilateral white-matter damage of immaturity (WMDI) we noticed a well preserved central VF despite a very thin GC+IPL. We speculate that this is due to plasticity in the immature visual system. Similar results were not noticed among cases with unilateral damage, acquired pre- or postnatally, in which the central VF was affected in most cases. OCT has proved to be a valuable targeted tool in children with damage to the retro-geniculate visual pathways, and that focal thinning of the GC+IPL predicts VF defects. This brief research report includes a review of four previously published papers. In addition, we present one new case and apply a recently developed classification system for CVI. The classification was applied on cases with bilateral WMDI to investigate its relation to retinal structure.