Alterations in white matter tract myelination in carriers of copy number variations at the 16p11.2 locus

Motivation: Individuals with 16p11.2 copy number variations (CNVs) have a heightened risk for neurodevelopmental disorders. Diffusion MRI studies have identified white matter alterations in 16p11.2 carriers; however, the exact neurobiological differences underlying these alterations remain unclear. Goal(s): To investigate white matter tract caliber and myelination in 16p11.2 CNV carriers. Approach: We analyzed 3T multi-modal quantitative MRI using tract-specific methods to minimize partial volume effects from crossing tracts. We used linear models to compare tract microstructural features between 16p11.2 CNV carriers and neurotypical controls. Results: Preliminary data indicate that gene dosage influences the g-ratio, increasing in 16p11.2 deletion carriers and decreasing in duplication carriers. Impact: This quantitative MRI study demonstrates for the first time that 16p11.2 CNV carriers exhibit altered myelination of their white matter tracts. Future work will investigate the association between network myelination and brain function.