Quantitative Grey/White Matter Myelin differences in Neurofibromatosis Type-1 using T1W/T2W ratio

Background: Neurofibromatosis-1 (NF1) is an autosomal dominant neurodevelopmental condition commonly characterised by learning difficulties, with co-occurring autism spectrum conditions in 30% and attention deficit hyperactivity disorder in about 50% of affected school-age children. The structural brain phenotype characteristically shows T2-white matter hyperintensities, particularly in the thalamus and basal ganglia, and previous diffusion MRI studies have demonstrated widespread white matter microstructural differences, suggesting aberrant myelination in NF1. However, no previous studies have investigated quantitative myelin in NF1. The aim of this study is to compare quantitative myelination in NF1 compared to neurotypical controls, and examine the relationship between myelin and working memory performance in children with NF1. Methods and materials: The T1-weighted and T2-weighted structural MRI images were acquired from 48 children and adolescents with NF1 aged 11-18 years. These were compared to data from 168 age- and gender-matched neurotypical controls drawn from the Human Connectome Project. Visuospatial n-back tasks were used to measure the working memory performance in the NF1 cohort. Pituitary depth was used as a covariate to control for pubertal differences. Results: Compared to neurotypicals, children with NF1 showed significantly reduced grey matter/white matter myelin ratios both throughout the brain and within each of the four major cerebral lobes. The stratified age-related whole-brain myelin differences were reduced in NF1 relative to controls. The sex-related whole-brain myelin differences were found to be greater in females than in males. However, no significant correlation was found between myelin and working memory performance in NF1. Pituitary depth was reduced in NF1 relative to controls. Conclusion: The reduced grey matter/white matter (GM/WM) myelin ratios in the whole brain and the frontal, temporal, parietal and occipital lobes suggests a widespread disruption of cerebral myelination in NF1. The age and sex-related myelin differences, and associated differences in developmental trajectories, may occur due to the effects of gonadal hormones but needs to be examined in future studies.