Decreased activity of piriform cortex and orbitofrontal hyperactivation in Usher Syndrome, a human disorder of ciliary dysfunction.

Usher syndrome (USH) is a condition characterized by ciliary dysfunction leading to retinal degeneration and hearing/vestibular loss. Putative olfactory deficits in humans have been documented at the psychophysical level and remain to be proven at the neurophysiological level. Thus, we aimed to study USH olfactory impairment using functional magnetic resonance imaging.

Enhanced Visual Attentional Modulation in Patients with Inherited Peripheral Retinal Degeneration in the Absence of Cortical Degeneration.

The role of attentional mechanisms in peripheral vision loss remains an outstanding question. Our study was aimed at determining the effect of genetically determined peripheral retinal dystrophy caused by Retinitis Pigmentosa (RP) on visual cortical function and tested the recruitment of attentional mechanisms using functional magnetic resonance imaging (fMRI). We included thirteen patients and twenty-two age- and gender-matched controls.

Early visual cortical structural changes in diabetic patients without diabetic retinopathy.

Background: It is known that diabetic patients have changes in cortical morphometry as compared to controls, but it remains to be clarified whether the visual cortex is a disease target, even when diabetes complications such as retinopathy are absent. Therefore, we compared type 2 diabetes patients without diabetic retinopathy with control subjects using magnetic resonance imaging to assess visual cortical changes when retinal damage is not yet present.

Methods: We performed T1-weighted imaging in 24 type 2 diabetes patients without diabetic retinopathy and 27 age- and gender-matched controls to compare gray matter changes in the occipital cortex between groups using voxel based morphometry.

Visual and ocular motor function in the atypical form of neurodegeneration with brain iron accumulation type I.

Background/aims: Neurodegeneration with brain iron accumulation (NBIA) type I is a rare disease that can be divided into a classical or atypical variant, according to age of onset and clinical pattern. Neuro-ophthalmological involvement has been documented in the classical variant but only anecdotically in the atypical variant. We sought to describe the visual and ocular motor function in patients with atypical form of NBIA type I.

Primary visual cortical remapping in patients with inherited peripheral retinal degeneration.

Human studies addressing the long-term effects of peripheral retinal degeneration on visual cortical function and structure are scarce. Here we investigated this question in patients with Retinitis Pigmentosa (RP), a genetic condition leading to peripheral visual degeneration. We acquired functional and anatomical magnetic resonance data from thirteen patients with different levels of visual loss and twenty-two healthy participants to study primary (V1) visual cortical retinotopic remapping and cortical thickness.

Genetically induced impairment of retinal ganglion cells at the axonal level is linked to extrastriate cortical plasticity.

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.

A New Approach to Assess Early Progressive Loss Across Multiple Visual Channels In the Natural History of Glaucoma.

Purpose: We aimed to evaluate the ability of new psychophysical discrimination tests, based on readily available hardware, to probe motion, achromatic, and chromatic contrast sensitivity, across the natural history of glaucoma. We assessed the sensitivity of these tests to detect functional damage at ocular hypertension stage, using receiver operating characteristic analysis. We also explored whether eccentricity-related patterns of damage change with disease progression.

Neuroretinal dysfunction with intact blood-retinal barrier and absent vasculopathy in type 1 diabetes.

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).

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.

Long term cortical plasticity in visual retinotopic areas in humans with silent retinal ganglion cell loss.

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.

Aging of low and high level vision: from chromatic and achromatic contrast sensitivity to local and 3D object motion perception.

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).

Physiological evidence for impairment in autosomal dominant optic atrophy at the pre-ganglion level.

Background: Functional studies in patients with autosomal dominant optic atrophy (ADOA) are usually confined to analysis of physiological and clinical impact at the ganglion cell (GG) and post GC levels. Here we aimed to investigate the impact of the disease at a pre-GC level and its correlation with GC/post-GC related measures.

Methods: Visual function was assessed in a population of 22 subjects (44 eyes) from 13 families with ADOA submitted to OPA1 mutation analysis.

Independent patterns of damage to retinocortical pathways in multiple sclerosis without a previous episode of optic neuritis.

Asymptomatic visual loss is a feature of multiple sclerosis (MS) but its relative impact on distinct retinocortical pathways is still unclear. The goal of this work was to investigate patterns of subclinical visual impairment in patients with MS with and without clinically associated previous optic neuritis (ON). We have used functional methods that assess parvo-, konio- and magnocellular pathways in order to compare pathophysiological mechanisms of damage in a population of 44 subjects with MS (87 eyes), with and without a previous episode of ON.

Asymmetry of visual sensory mechanisms: electrophysiological, structural, and psychophysical evidences.

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.

Retinal function in best macular dystrophy: relationship between electrophysiological, psychophysical, and structural measures of damage.

Purpose: To establish structure-function correlations across the visual field, to investigate disease progression in Best macular dystrophy (BMD), by correlating structural damage with retinal function as assessed by the combination of psychophysics and multifocal electrophysiology.

Methods: Spatial achromatic and chromatic contrast sensitivities (probing red-green and blue-yellow pathways) were assessed using custom-made psychophysical software to evaluate retinal damage in BMD and age-matched control eyes (n = 19 and n = 22, respectively). Neurosensory retinal dysfunction was also evaluated by means of multifocal electroretinography (mfERG).

Evidence of widespread retinal dysfunction in patients with stargardt disease and morphologically unaffected carrier relatives.

Purpose: To characterize contrast sensitivity (CS) across the visual field for two achromatic spatial-temporal frequencies in 21 families with Stargardt disease (STGD) and to correlate psychophysical impairment with patterns of change in multifocal electroretinography (mfERG).

Methods: Twenty-seven eyes from patients with STGD, 16 eyes from asymptomatic relatives, and 44 age-matched control eyes were included. Chromatic CS function was assessed by comparing protan, deutan, and tritan (Cambridge Color Test; Cambridge Research Systems Ltd.

Visual phenotype in Williams-Beuren syndrome challenges magnocellular theories explaining human neurodevelopmental visual cortical disorders.

Williams-Beuren syndrome (WBS), a neurodevelopmental genetic disorder whose manifestations include visuospatial impairment, provides a unique model to link genetically determined loss of neural cell populations at different levels of the nervous system with neural circuits and visual behavior. Given that several of the genes deleted in WBS are also involved in eye development and the differentiation of retinal layers, we examined the retinal phenotype in WBS patients and its functional relation to global motion perception. We discovered a low-level visual phenotype characterized by decreased retinal thickness, abnormal optic disk concavity, and impaired visual responses in WBS patients compared with age-matched controls by using electrophysiology, confocal and coherence in vivo imaging with cellular resolution, and psychophysics.