Investigation of brain structure in the 1-month infant

Abstract

The developing brain undergoes systematic changes that occur at successive stages of maturation. Deviations from the typical neurodevelopmental trajectory are hypothesized to underlie many early childhood disorders; thus, characterizing the earliest patterns of normative brain development is essential. Recent neuroimaging research provides insight into brain structure during late childhood and adolescence; however, few studies have examined the infant brain, particularly in infants under 3 months of age. Using high-resolution structural MRI, we measured subcortical gray and white matter brain volumes in a cohort (N = 143) of 1-month infants and examined characteristics of these volumetric measures throughout this early period of neurodevelopment. We show that brain volumes undergo age-related changes during the first month of life, with the corresponding patterns of regional asymmetry and sexual dimorphism. Specifically, males have larger total brain volume and volumes differ by sex in regionally specific brain regions, after correcting for total brain volume. Consistent with findings from studies of later childhood and adolescence, subcortical regions appear more rightward asymmetric. Neither sex differences nor regional asymmetries changed with gestation-corrected age. Our results complement a growing body of work investigating the earliest neurobiological changes associated with development and suggest that asymmetry and sexual dimorphism are present at birth.

Keywords: Brain asymmetry; Brain volume; Magnetic resonance imaging; Sexual dimorphism.

Figure 1

Overview of the image processing and volume calculation pipeline. Upon acquisition and inspection of T₁- and T₂-weighted images, non-parenchyma tissue is removed and images are aligned to the study-specific template. Subcortical gray matter and white matter atlas priors are then inverse warped to the infant native space and regional volumes are computed.

Figure 2

(Top row) Representative axial and coronal views of the study-specific T₁-weighted and T₂-weighted templates generated from 1-month old infant brain data. (Middle row) Subcortical gray matter and (Bottom row) white matter regions used for volumetric measurement. Regions are overlaid on the T₁-weighted template and separated by color.

Figure 3

Individual T₁- and T₂-weighted images aligned to the study specific template space, with subcortical gray and white matter priors overlaid on the individual’s T₁-weighted image. Subcortical gray matter and white matter regions are color-coded as in Figure 2. These representative images demonstrate the ability of the symmetric diffeomorphic registration to successfully map T₁- and T₂-weighted images to the study-specific template space, while quantitative assessment of overlap shows evidence for good agreement between atlas and individual priors (Supplementary Table 1).

Figure 4

Correlations between infant brain volumes measured using T₁-weighted and T₂-weighted images (for comparison with multivariate normalization, see Supplementary Figures 1 and 2). Estimated volumes were found to all be highly correlated and thus we used measurements from both T₁- and T₂-weighted images.

Figure 5

Association between gestation corrected and total brain volume, white matter volume, and gray matter volume for males (blue) and females (red). Total brain volume was observed to significantly increase (p<0.05, Bonferroni corrected) in both males and females, though this rate of increase did not differ between the two sexes.