The neuronal mechanism of visual agnosia and foveal crowding that underlies the behavioral symptoms of several classic neurodegenerative diseases, including impaired holistic perception, navigation, and reading, is still unclear. A better understanding of this mechanism is expected to lead to better treatment and rehabilitation.OBJECTIVE To use state-of-the-art neuroimaging protocols to assess a hypothesis that abnormal population receptive fields (pRF) in the visual cortex underlie high-order visual impairments.DESIGN, SETTING, AND PARTICIPANTS Between April 26 and November 21, 2016, patients and controls were recruited from the Hadassah-Hebrew University medical center in a cross-sectional manner. Six patients with posterior cortical atrophy (PCA) were approached and 1 was excluded because of an inability to perform the task. Participants underwent functional magnetic resonance imaging-based cortical visual field mapping and pRF evaluation and performed a masked repetition priming task to evaluate visuospatial perception along the eccentricity axis. The association between pRF sizes and behavioral impairments was assessed to evaluate the role of abnormal pRF sizes in impaired visual perception. Posterior cortical atrophy is a visual variant of Alzheimer disease that is characterized by progressive visual agnosia despite almost 20/20 visual acuity. Patients with PCA are rare but invaluable for studying visual processing abnormalities following neurodegeneration, as atrophy begins in visual cortices but initially spares other brain regions involved in memory and verbal communication.EXPOSURES Participants underwent a magnetic resonance imaging scan. MAIN OUTCOMES AND MEASURESPopulation receptive field sizes and their association with visual processing along the fovea-to-periphery gradient.RESULTS Five patients with PCA (4 men [80%]; mean [SEM] age, 62.9 [3.5] years) were compared with 8 age-matched controls (1 man [25%]; mean [SEM] age, 63.7 [3.7] years) and demonstrated an atypical pRF mapping that varied along the eccentricity axis, which presented as abnormally small peripheral and large foveal pRFs sizes. Abnormality was seen in V1 (peripheral, 4.4°and 5.5°; foveal, 5.5°and 4.5°in patients and controls, respectively; P < .05) as well as in higher visual regions, but not in intermediate ones. Behaviorally, an atypical fovea-to-periphery gradient in visual processing was found that correlated with their pRF properties (r = 0.8; P < .01 for the correlation between pRF and behavioral fovea-to-periphery slopes).CONCLUSIONS AND RELEVANCE High-order visuocognitive functions may depend on abnormalities in basic cortical characteristics. These results may fundamentally change approaches to rehabilitation in such conditions, emphasizing the potential of low-level visual interventions.

Most individuals with congenital achromatopsia (ACHM) carry mutations that affect the retinal phototransduction pathway of cone photoreceptors, fundamental to both high acuity vision and colour perception. As the central fovea is occupied solely by cones, achromats have an absence of retinal input to the visual cortex and a small central area of blindness. Additionally, those with complete ACHM have no colour perception, and colour processing regions of the ventral cortex also lack typical chromatic signals from the cones. This study examined the cortical morphology (grey matter volume, cortical thickness, and cortical surface area) of multiple visual cortical regions in ACHM (n = 15) compared to normally sighted controls (n = 42) to determine the cortical changes that are associated with the retinal characteristics of ACHM. Surface-based morphometry was applied to T1-weighted MRI in atlas-defined early, ventral and dorsal visual regions of interest. Reduced grey matter volume in V1, V2, V3, and V4 was found in ACHM compared to controls, driven by a reduction in cortical surface area as there was no significant reduction in cortical thickness. Cortical surface area (but not thickness) was reduced in a wide range of areas (V1, V2, V3, TO1, V4, and LO1). Reduction in early visual areas with large foveal representations (V1, V2, and V3) suggests that the lack of foveal input to the visual cortex was a major driving factor in morphological changes in ACHM. However, the significant reduction in ventral area V4 coupled with the lack of difference in dorsal areas V3a and V3b suggest that deprivation of chromatic signals to visual cortex in ACHM may also contribute to changes in cortical morphology. This research shows that the congenital lack of cone input to the visual cortex can lead to widespread structural changes across multiple visual areas.

Highlights Anatomy of primary visual cortex (V1) assessed with surface-based morphmetry in those with congenital achromatopsia (ACHM). Reduction in cortical surface area in foveal, parafoveal and paracentral representations of V1 in those with ACHM. In ACHM a localized thickening in the area of V1 that represents the region of retina occupied solely by cones. V1 changes in ACHM may limit its ability to take on normal properties if retinal function were to be restored. Early intervention, before the development plastic period is over, may offer better restoration of vision in ACHM.

PURPOSE. The neural substrate of binocularity and sighting ocular dominance in humans is not clear. By utilizing the population receptive field (pRF) modeling technique, we explored whether these phenomena are associated with amplitude and pRF size differences. METHODS. The visual field maps of 13 subjects were scanned (3-T Skyra) while viewing drifting bar stimuli. Both eyes (binocular condition), the dominant eye and the nondominant eye (two monocular conditions) were stimulated in separate sessions. For each condition, pRF size and amplitude were assessed. Binocular summation ratios were calculated by dividing binocular by mean monocular values (amplitude and pRF size). RESULTS. No differences in pRF size were seen between the viewing conditions within each region, that is, either between binocular and monocular or between dominant and nondominant viewing conditions. Binocular amplitudes were higher than the monocular amplitudes, but similar among the dominant and nondominant eyes. Binocular summation ratios derived from amplitudes were significantly higher than one (~1.2), while those ratios derived from pRF size were not. These effects were found in all studied areas along the visual hierarchy, starting in V1. CONCLUSIONS. Neither the amplitude nor the pRF size show intereye difference and therefore cannot explain the different roles of the dominant and the nondominant eyes. Binocular, as compared to monocular vision, resulted in higher amplitudes, while receptive fields' sizes were similar, suggesting increased binocular response intensity as the basis for the binocular summation phenomenon. Our results could be applicable in imaging studies of monocular disease and studies that deal with nondisparity binocularity effects.

Autosomal recessive Achromatopsia (ACHM) is a rare inherited disorder associated with dysfunctional cone photoreceptors resulting in a congenital absence of cone input to visual cortex. This might lead to distinct changes in cortical architecture with a negative impact on the success of gene augmentation therapies. To investigate the status of the visual cortex in these patients, we performed a multi-centre study focusing on the cortical structure of regions that normally receive predominantly cone input. Using high-resolution T1-weighted MRI scans and surface-based morphometry, we compared cortical thickness, surface area and grey matter volume in foveal, parafoveal and paracentral representations of primary visual cortex in 15 individuals with ACHM and 42 normally sighted, healthy controls (HC). In ACHM, surface area was reduced in all tested representations, while thickening of the cortex was found highly localized to the most central representation. These results were comparable to more widespread changes in brain structure reported in congenitally blind individuals, suggesting similar developmental processes, i.e., irrespective of the underlying cause and extent of vision loss. Our findings indicate that there may be an optimum time window for gene therapy to counteract developmental cortical changes related to the absence of sensory input.