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

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.