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

Abstract

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.

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

“…Our prediction therefore would be that cortical thickening would be observed only in representations of the central visual field. Indeed, our preliminary analysis has found increased cortical thickness in the most central representations of primary visual cortex in ACHM ( Molz et al, 2021 ). It remains to be seen if a total absence of input from the central fovea results in thickening of the foveal representation within higher visual areas.…”

“…All of these areas also process colour information ( Mullen et al, 2007 ; Railo et al, 2012 ; Hurme et al, 2020 ), which could contribute further reductions in these areas. In a separate study, we have extended our analysis to investigate more specifically the eccentricity dependence of structural changes within primary visual cortex and shows that cortical changes are most pronounced in central visual field representations (manuscript submitted and under review; preprint available under Molz et al, 2021 ).…”