Andrew Alexander, PhD – Slide of the Week

Andrew Alexander, PhD - Slide of the Week

Title: Heritability of Brain White Matter Microstructure

Legend: Maps of the Intraclass Correlation Coefficient (ICC) for monozygotic (MZ – top row) and dizygotic (DZ – middle row) twins and the computed Falconer’s Heritability (1 = completely inherited, bottom row) for diffusion MRI neurite density (ND), neurite orientation dispersion index (ODI) and fractional anisotropy (FA).   ND shows the highest heritability.

Citation: Luo, Z., Adluru, N., Dean, D. C., 3rd, Alexander, A. L., & Goldsmith, H. H. (2022). Genetic and environmental influences of variation in diffusion MRI measures of white matter microstructure. Brain structure & function, 227(1), 131–144.

Abstract: Quantitative neuroimaging studies in twin samples can investigate genetic contributions to brain structure and microstructure. Diffusion tensor imaging (DTI) studies with twin samples have shown moderate to high heritability in white matter microstructure. This study investigates the genetic and environmental contributions of another widely used diffusion MRI model not yet applied to twin studies, neurite orientation dispersion and density imaging (NODDI). The NODDI model is a multicompartment model of the diffusion-weighted MRI signal, providing estimates of neurite density (ND) and the orientation dispersion index (ODI). A cohort of monozygotic (MZ) and same-sex dizygotic (DZ) twins (N = 460 individuals) between 13 and 24 years of age were scanned with a multi-shell diffusion weighted imaging protocol. Select white matter (WM) regions of interest (ROI) were extracted. Biometric structural equation modeling estimated the relative contributions from additive genetic (A) and common (C) and unique environmental (E) factors. Genetic factors for the NODDI measures accounted for 91% and 65% of the variation of global ND and ODI, respectively, compared with 83% for FA. We observed higher heritability for ND than both FA and ODI in 25 of 30 discrete white matter regions that we examined, suggesting ND may be more sensitive to underlying genetic sources of variation. This study demonstrated that genetic factors play a key role in the development of white matter microstructure using both DTI and NODDI.

About the Lab: Alexander’s research focuses on the use of magnetic resonance imaging (MRI) for mapping and measuring the functional and structural organization of the human brain. These techniques are used to investigate the brain in both typically developing individuals and subjects with developmental disorders including autism. Functional MRI (fMRI) is used to assess brain regions associated with cognition and affect and their dysfunctions in these populations. Diffusion tensor MRI (DT-MRI) is used to study the patterns of structural connectivity between brain activity regions. Anatomic imaging methods are used to assess longitudinal structural changes in brain regions. These measurements are ultimately compared with measures of affect, behavior and cognition in specific population groups.

Investigator: Andrew Alexander, PhD

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