Longitudinal Study of the Emerging Functional Connectivity Asymmetry of Primary Language Regions during Infancy

Robert W Emerson, Wei Gao, Weili Lin, Robert W Emerson, Wei Gao, Weili Lin

Abstract

Asymmetry in the form of left-hemisphere lateralization is a striking characteristic of the cerebral regions involved in the adult language network. In this study, we leverage a large sample of typically developing human infants with longitudinal resting-state functional magnetic resonance imaging scans to delineate the trajectory of interhemispheric functional asymmetry in language-related regions during the first 2 years of life. We derived the trajectory of interhemispheric functional symmetry of the inferior frontal gyrus (IFG) and superior temporal gyrus (STG), the sensory and visual cortices, and two higher-order regions within the intraparietal sulcus and dorsolateral prefrontal cortex. Longitudinal models revealed a best fit with quadratic age terms and showed significant estimated coefficients of determination for both the IFG (r2 = 0.261, p < 0.001) and the STG (r2 = 0.142, p < 0.001) regions while all other regions were best modeled by log-linear increases. These inverse-U-shaped functions of the language regions peaked at ∼11.5 months of age, indicating that a transition toward asymmetry began in the second year. This shift was accompanied by an increase in the functional connectivity of these regions within the left hemisphere. Finally, we detected an association between the trajectory of the IFG and language outcomes at 4 years of age (χ2 = 10.986, p = 0.011). Our results capture the developmental timeline of the transition toward interhemispheric functional asymmetry during the first 2 years of life. More generally, our findings suggest that increasing interhemispheric functional symmetry in the first year might be a general principle of the developing brain, governing different functional systems, including those that will eventually become lateralized in adulthood.

Significance statement: Cross-sectional studies of the language system in early infancy suggest that the basic neural mechanisms are in place even before birth. This study represents the first of its kind, using a large longitudinal sample of infants, to delineate the early language-related transition toward interhemispheric functional asymmetry in the brain using resting-state functional MRI. More generally, our findings suggest that increasing interhemispheric functional symmetry in the first year might be a general principle of the developing brain governing multiple functional systems, including those that will eventually become lateralized in adulthood. Although resting-state functional MRI cannot provide direct insights into the developmental mechanisms of language lateralization, this study reveals language-related functional connectivity changes during infancy, marking critical points in the development of the brain's functional architecture.

Keywords: cognitive development; functional asymmetry; functional connectivity; infancy; language network.

Copyright © 2016 the authors 0270-6474/16/3610883-10$15.00/0.

Figures

Figure 1.
Figure 1.
ROIs on an MNI template brain. The spherical ROIs used in the analysis are projected onto an MNI template brain. These regions include language-related regions in the inferior frontal gyrus (IFG; yellow) and the superior temporal gyrus (STG; red). Additionally, the lingual gyrus (purple), the somatosensory regions (orange), the intraparietal sulcus (IPS; blue), and the dorsolateral prefrontal cortex (DLPFC; green) are shown. The longitudinal registrations of these regions to each age-specific template are also displayed in a matching color scheme.
Figure 2.
Figure 2.
Average symmetrical connectivity strength for each age group. Average symmetrical connectivity strength is shown for each age group, separated by months since birth. Blue bars represent the first year, followed by the second year shown in green. A total of 223 subject data points are represented. SE bars are shown.
Figure 3.
Figure 3.
Longitudinal growth curves of symmetric connectivity strength. A, B, Red lines indicate the fitted curve of the best model for language-related regions (A), primary somatosensory and visual regions (B), and the dorsolateral prefrontal cortex (DLPFC) and intraparietal sulcus (IPS; B). Age shows months since birth. A total of 223 subject data points are represented for each region. Symmetrical Connectivity Strength is represented by the fisher-z transformed correlations between homologue regions.
Figure 4.
Figure 4.
Intrahemispheric connectivity between the left IFG and STG. Connectivity between the IFG and STG increases in a log-linear fashion over the first 2 years. A total of 223 subject data points are represented.
Figure 5.
Figure 5.
The association between the developmental trajectory of symmetric connectivity and language outcomes in the IFG. Each point represents the symmetrical connectivity strength for an individual at a specific age. The black line represents the trajectory predicted by an average language score. The green line represents the trajectory predicted with a language score 1 SD above the mean, while the red line represents 1 SD below the mean. The age of peak for each estimated curve is as follows: average (black), 665 d; high (green), 650 d; low (red), 686 d.

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