Functional connectivity for the language network in the developing brain: 30 weeks of gestation to 30 months of age

Abstract

Although the neural scaffolding for language is putatively present before birth, the maturation of functional connections among the key nodes of the language network, Broca's and Wernicke's areas, is less known. We leveraged longitudinal and cross-sectional data from three sites collected through six studies to track the development of functional circuits between Broca's and Wernicke's areas from 30 weeks of gestation through 30 months of age in 127 unique participants. Using resting-state fMRI data, functional connectivity was calculated as the correlation between fMRI time courses from pairs of regions, defined as Broca's and Wernicke's in both hemispheres. The primary analysis evaluated 23 individuals longitudinally imaged from 30 weeks postmenstrual age (fetal) through the first postnatal month (neonatal). A secondary analysis in 127 individuals extended these curves into older infants and toddlers. These data demonstrated significant growth of interhemispheric connections including left Broca's and its homolog and left Wernicke's and its homolog from 30 weeks of gestation through the first postnatal month. In contrast, intrahemispheric connections did not show significant increases across this period. These data represent an important baseline for language systems in the developing brain against which to compare those neurobehavioral disorders with the potential fetal onset of disease.

Keywords: fetal; infant; neonate; perinatal transition; trajectory.

Figure 1

Maturation of the overall language network over the third trimester and first postnatal month. A) Seeds and connections averaged together create the overall language network connectivity. As the Broca’s and Wernicke’s area seeds are on different axial slices, the white line in the brain indicates that two different slices are being shown in a single visualization. B) Estimates of connectivity strength at the anchors for the piecewise linear growth curve (31.3 weeks (PMA31), 35.7 weeks (PMA36), 40.0 weeks (PMA40), and 44.3 weeks (PMA44) PMA). Error bars represent 95% confident intervals. Lines indicate longitudinal data from the same participant scanned at multiple time points.

Figure 2

Maturation of the interhemispheric and intrahemispheric language connections over the third trimester and first postnatal month. Seeds and connection used to calculate connectivity between and estimates of connectivity strength at the anchors for the piecewise linear growth curve for A) Broca’s area and its right hemisphere homolog, B) Wernicke’s area and its right hemisphere homolog, C) Broca’s and Wernicke’s area, and D) the right hemisphere homologs of Broca’s and Wernicke’s area. For all plots, anchors are 31.3 weeks (PMA31), 35.7 weeks (PMA36), 40.0 weeks (PMA40), and 44.3 weeks (PMA44) PMA. Error bars represent 95% confident intervals. Lines indicate longitudinal data from the same participant scanned at multiple time points. As the Broca’s and Wernicke’s area seeds are on different axial slices, the white line in the brain indicates that two different slices are being shown in a single visualization.

Figure 3

Maturation of the interhemispheric connectivity for Broca’s and Wernicke’s area over the third trimester and first postnatal month. Seed-to-whole brain, using Broca’s and Wernicke’s areas as seeds, shows that interhemispheric connections between homologs were only observed for the postnatal scan.

Figure 4

Maturation of the overall language network from 30 weeks gestation to 30 months. A) Seeds and connections averaged together create the overall language network connectivity. As the Broca’s and Wernicke’s area seeds are on different axial slices, the white line in the brain indicates that two different slices are being shown in a single visualization. B) Estimates of connectivity strength at the anchors, −2 (i.e., 31.3 weeks PMA), 1, 9, 18, and 30 months, for the piecewise linear growth curve. Error bars represent 95% confident intervals. Lines indicate longitudinal data from the same participant scanned at multiple time points.