Intersubject variability of and genetic effects on the brain's functional connectivity during infancy

Abstract

Infancy is a period featuring a high level of intersubject variability but the brain basis for such variability and the potential genetic/environmental contributions remain largely unexplored. The assessment of the brain's functional connectivity during infancy by the resting state functional magnetic resonance imaging (rsfMRI) technique (Biswal et al., 1995) provides a unique means to probe the brain basis of intersubject variability during infancy. In this study, an unusually large typically developing human infant sample including 58 singletons, 132 dizygotic twins, and 98 monozygotic twins with rsfMRI scans during the first 2 years of life was recruited to delineate the spatial and temporal developmental patterns of both the intersubject variability of and genetic effects on the brain's functional connectivity. Through systematic voxelwise functional connectivity analyses, our results revealed that the intersubject variability at birth features lower variability in primary functional areas but higher values in association areas. Although the relative pattern remains largely consistent, the magnitude of intersubject variability undergoes an interesting U-shaped growth during the first 2 years of life. Overall, the intersubject variability patterns during infancy show both adult-like and infant-specific characteristics (Mueller et al., 2013). On the other hand, age-dependent genetic effects were observed showing significant but bidirectional relationships with intersubject variability. The temporal and spatial patterns of the intersubject variability of and genetic contributions to the brain's functional connectivity documented in this study shed light on the largely uncharted functional development of the brain during infancy.

Keywords: early brain development; functional connectivity; genetic effects; infancy; intersubject variability; resting state.

Copyright © 2014 the authors 0270-6474/14/3411288-09$15.00/0.

Figures

Figure 1.

Intersubject variability pattern of the brain's functional connectivity during infancy (singletons). A, Intersubject variability map of the brain's functional connectivity in neonates (top row), 1-year-olds (middle row), and 2-year-olds (bottom row); values were demeaned (the mean values are labeled at the middle of the color bars): cool colors represent values below the whole-brain mean intersubject variability and warm colors represent values greater than the mean. B, Areas showing statistically significant changes (p < 0.05 after cluster-size multiple-comparisons correction) in intersubject variability of the brain's functional connectivity during the first year (top row) and second year of life (bottom row). C, Network-level intersubject variability of the brain's functional connectivity at 1 month measured based on singleton subjects. D, Network-level intersubject variability of the brain's functional connectivity at 12 months measured based on singleton subjects. E, Network-level intersubject variability of the brain's functional connectivity at 24 months measured based on singleton subjects. F, Developmental changes in network-level intersubject variability during the first year of life. G, Developmental changes in network-level intersubject variability during the second year of life. Dashed lines for C–G correspond with the mean (C–E)/mean changes (F, G) of intersubject variability of all voxels in the brain. Error bars represent SEM of voxels within network masks.

Figure 2.

Variability maps (not demeaned) of singletons, DZ twins, and MZ twins for the three age groups.

Figure 3.

Relationships between intersubject variability of the brain's functional connectivity and distant/local connectivity during infancy.

Figure 4.

Genetic effects on the brain's functional connectivity during infancy. A, Comparison of the intersubject variability the brain's functional connectivity between singleton pairs (SG, top row), DZ twin (middle row), MZ twin (bottom row) pairs. The values of DZ and MZ pairs were normalized against those of the singleton pairs to show their relative strength. B, Genetic coefficient maps based on GLM modeling of the genetic effects on the brain's functional connectivity. C, Areas showing statistically significant genetic effects (p < 0.05 after cluster-wise multiple-comparisons correction) in each of the three age groups. D, Areas showing statistically significant effects of shared environment (p < 0.05 after cluster-wise multiple-comparisons correction) in each of the three age groups. E, Relative ranking of different functional networks in genetic effects for all three age groups. F, Developmental changes in network-level genetic effects during the first year of life. G, Developmental changes in network-level genetic effects during the second year of life. Dashed lines in E–G correspond with the mean (E)/mean genetic changes (F, G) of all networks. Error bars represent SEM.

Figure 5.

Relationship between the intersubject variability of and genetic effects on the brain's functional connectivity. Areas with statistically significant (p < 0.05 after multiple-comparison correction) positive (red) and negative (blue) correlations between intersubject variability and genetic effects are visualized for the three age groups.