Structural Differences Across Multiple Visual Cortical Regions in the Absence of Cone Function in Congenital Achromatopsia

Abstract

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.

Structural changes to primary visual cortex in the congenital absence of cone input in achromatopsia

“…We hypothesise that individuals with ACHM will show distinct changes in cortical anatomy particularly in central visual field representations of primary visual cortex that have been deprived of normal cone input throughout development. This detailed analysis of the first and largest visual representation in the human brain complements our previous analysis of a larger number of visual areas of the occipital lobe ( Lowndes et al, 2021 ).…”

“…However, it is possible that higher order visual processing regions are also affected, particularly those that rely on cone input to process colour, patterns and form/shape. A recent study compared structural differences more broadly in the dorsal and ventral visual processing pathways of the brain in ACHM, reporting a reduction in overall cortical surface area in several visual areas (V1, V2, V3, TO1, hV4, and LO1) ( Lowndes et al, 2021 ).…”

“…Experimental protocols received approval from the site-specific ethics committees and were in accordance with the Declaration of Helsinki. A previous study analyzing the data from the same participants has been published ( Lowndes et al, 2021 ). A larger number of occipital lobe visual areas were assessed in that work, but it did not test for anatomical changes in difference eccentricity representations – the key aspect of the work presented here.…”

Assessing the structure of the posterior visual pathway in bilateral macular degeneration

“…We have found cross sectional evidence of atrophic changes in the cortex, while others have reported a loss in integrity of the optic radiations. In this study, we have acquired data over a 2-year period to determine whether there are changes to the visual cortex and optic radiations over time.In cases of vision loss, atrophy of the posterior visual pathway, greater than that observed with ageing has been reported [1][2][3][4][5][6][7][8][9][10][11][12][13] . Given the retinotopic organisation of visual cortex, when macular degeneration (MD) is present in both eyes, resulting in overlapping visual defects, the cortical representation of the visual defect lacks sensory input; reductions in cortical thickness and volume in this representation have been reported in both juvenile MD (JMD) and age-related MD (AMD) 5,11,12,[14][15][16][17] .In addition to assessments of grey matter thickness and volume, advances in neuroimaging have allowed for the evaluation of more subtle changes in microstructure, macrostructure and anatomical connectivity in vivo, making it a valuable technique to assess cortical myelin and white matter changes in detail 10,[18][19][20][21][22] .…”

“…In cases of vision loss, atrophy of the posterior visual pathway, greater than that observed with ageing has been reported [1][2][3][4][5][6][7][8][9][10][11][12][13] . Given the retinotopic organisation of visual cortex, when macular degeneration (MD) is present in both eyes, resulting in overlapping visual defects, the cortical representation of the visual defect lacks sensory input; reductions in cortical thickness and volume in this representation have been reported in both juvenile MD (JMD) and age-related MD (AMD) 5,11,12,[14][15][16][17] .…”