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

Abstract

Achromatopsia (ACHM), a rare autosomal recessive visual disorder, is characterized by a loss of cone signal transduction. This results in a congenital absence of visual input from cone photoreceptors, which dominate the foveal retina, to primary visual cortex, potentially affecting the integrity of visual cortical macrostructure. As current retinal gene augmentation therapies rely on intact cortical anatomy, the aim of this multi-centre study was to determine the status of primary visual cortex in this patient population. We used high resolution T1-weighted 3T MRI scans (1mm isotropic resolution) and surface-based morphometry to compare cortical thickness, surface area and grey matter volume in primary visual cortex in 15 ACHM participants and 42 healthy controls within three regions-of-interest (foveal: 0-2deg, parafoveal: 2-4deg, paracentral: 4-8deg). Grey matter volume was significantly reduced only in the paracentral representation (ΔR2 = 8.8%; (F (1,50) = 5.398, p = .024), while surface area was reduced across foveal (ΔR2 = 4.2 %; F(1,50) = 5.651, p = .021), parafoveal (ΔR2 = 5.5 %; F(1,50) = 4.846, p = .032) and paracentral representations (ΔR2 = 17.6%; F (1,50) =12.851, p = .001) of primary visual cortex. In contrast, a thickening of visual cortex was found only in the foveal region representing the absolute scotoma (ΔR2 = 7.4%; (F (1,50) = 6.173, p = .016). These findings are comparable to more widespread anatomical differences reported in other congenital visual disorders, indicating a possible common mechanism underlying changes during cortical development. Overall, these results suggest that early intervention is favourable to counteract any developmental changes caused by the missing sensory input in ACHM.