Morphometric Changes of the Corpus Callosum in Congenital Blindness

We examined the effects of visual deprivation at birth on the development of the corpus callosum in a large group of congenitally blind individuals. We acquired high-resolution T1-weighted MRI scans in 28 congenitally blind and 28 normal sighted subjects matched for age and gender. There was no overall group effect of visual deprivation on the total surface area of the corpus callosum. However, subdividing the corpus callosum into five subdivisions revealed significant regional changes in its three most posterior parts. Compared to the sighted controls, congenitally blind individuals showed a 12 reduction in the splenium, and a 20 increase in the isthmus and the posterior part of the body. A shape analysis further revealed that the bending angle of the corpus callosum was more convex in congenitally blind compared to the sighted control subjects. The observed morphometric changes in the corpus callosum are in line with the well-described cross-modal functional and structural neuroplastic changes in congenital blindness

Are supramodality and cross-modal plasticity the yin and yang of brain development? From blindness to rehabilitation

Research in blind individuals has primarily focused for a long time on the brain plastic reorganization that occurs in early visual areas. Only more recently, scientists have developed innovative strategies to understand to what extent vision is truly a mandatory prerequisite for the brain’s fine morphological architecture to develop and function. As a whole, the studies conducted to date in sighted and congenitally blind individuals have provided ample evidence that several ‘visual’ cortical areas develop independently from visual experience and do process information content regardless of the sensory modality through which a particular stimulus is conveyed: a property named supramodality. At the same time, lack of vision leads to a structural and functional reorganization within 'visual' brain areas, a phenomenon known as cross-modal plasticity. Cross-modal recruitment of the occipital cortex in visually deprived individuals represents an adaptative compensatory mechanism that mediates processing of non-visual inputs. Supramodality and cross-modal plasticity appear to be the 'yin and yang' of brain development: supramodal is what takes place despite the lack of vision, whereas cross-modal is what happens because of lack of vision. Here we provide a critical overview of the research in this field and discuss the implications that these novel findings have for the development of educative/rehabilitation approaches and sensory substitution devices in sensory-impaired individuals

Cortical thickness of primary visual cortex correlates with motion deficits in periventricular leukomalacia

Abstract Impairments of visual motion perception and, in particular, of flow motion have been consistently observed in premature and very low birth weight subjects during infancy. Flow motion information is analyzed at various cortical levels along the dorsal pathways, with information mainly provided by primary and early visual cortex (V1, V2 and V3). We investigated the cortical stage of the visual processing that underlies these motion impairments, measuring Grey Matter Volume and Cortical Thickness in 13 children with Periventricular Leukomalacia (PVL). The cortical thickness, but not the grey matter volume of area V1, correlates negatively with motion coherence sensitivity, indicating that the thinner the cortex, the better the performance among the patients. However, we did not find any such association with either the thickness or volume of area MT, MST and areas of the IPS, suggesting damage at the level of primary visual cortex or along the optic radiation

Long-term effects of pre-and postnatal glucocorticoid treatment in congenital adrenal hyperplasia

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder mostly caused by mutations in the CYP21A2 gene leading to impaired production of cortisol and aldosterone. Precursors in the steroidogenic pathway are shunted to pathways of androgen production and elevated levels of androgens may cause virilization of the external genitalia in females with CAH already in utero. Prenatal treatment with the synthetic glucocorticoid (GC) dexamethasone (DEX) can ameliorate virilization of the female fetus but because of the recessive mode of the inheritance of CAH and that treatment has to be initiated before the genotype of the fetus can be determined, the majority of the treated cases will be unnecessarily exposed to DEX during fetal life. Moreover, patients with CAH require GC replacement therapy after birth and during their life span there may be episodes of over- or under-treatment with a risk of developing adverse effects. Side effects of pre-and postnatal GC exposure may develop into chronic conditions with permanent effects on growth, metabolism, cognition, behavior and normal immune functioning. In this study, the effects of prenatal DEX treatment and postnatal GC treatment in the context of CAH were evaluated in a cohort of 265 individuals. The cohort comprised DEX-treated individuals with and without CAH, patients with CAH not prenatally treated with DEX and controls from the general population. The long-term impact on cognition, behavior, brain morphology, metabolism and DNA methylation was studied. Prenatal treatment with DEX was associated with cognitive impairments, particularly working memory. The effects seem to normalize by adult age in individuals without CAH who were treated with DEX during the first trimester of fetal life. In patients with CAH, prenatal DEX therapy was associated with reduced thickness and surface area bilaterally of a large area encompassing the parietal and superior occipital cortex. Moreover, the effects of DEX treatment on DNA methylation were associated with alterations in the DNA methylation profile, denoting an altered epigenetic programming of the immune system and, in particular, inflammation in individuals without CAH treated in the first trimester. This finding may confer altered risks for immune-related disorders later in life. When looking at the long-term outcome in patients with CAH, patients showed deficits in tests measuring executive functioning. Deficits in spatial working memory were associated with decreased white matter integrity that, in turn, was associated with lower dosages of GCs. Patients also showed structural alterations in the prefrontal regions involved in executive functioning and in areas of the parietal and superior occipital cortex involved in sensory integration. In addition, patients exhibited reduced cerebellar volume. In our analysis of DNA methylation in patients with CAH, we identified hypermethylation in two CpGs in two genes (FAIM2 and SFI1). Methylation was associated with the severity of CAH and brain structure, but we could not identify any association between methylation in these two genes and metabolic or cognitive outcome. In conclusion, this study extends our knowledge about the effects of pre-and postnatal GC treatment in CAH. The results have implications for the use of prenatal DEX treatment