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

Abstract

AbstractAutosomal 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.HighlightsWe assessed cortical anatomy of a large cohort of patients with genetically confirmed cone photoreceptor dysfunction (achromatopsia) using surface-based morphometry.We found widespread reduction in cortical surface area across foveal, parafoveal and paracentral proportions of primary visual cortex in participants with achromatopsia.highly localized cortical thickening in participants with achromatopsia at the region of visual cortex that lacked inputs from the retinal region occupied solely by cones.Further evidence that the visual cortex is unlikely to take on normal properties if vision were restored after the developmental plastic period.Early intervention is preferable when considering vision restoration treatment in achromatopsia.