The emergence of a functionally flexible brain during early infancy

Significance While adult brains are known to be functionally flexible, the emergence of a functionally flexible brain during early infancy is largely uncharted due the lack of approaches to assess neural flexibility in infants. Using recent advances of multilayer network approaches and a cohort of typically developing children who underwent longitudinal MRI during the first 2 y of life, we investigated the developmental characteristics of brain neural flexibility. The temporal and spatial emergence of a functionally flexible brain was revealed. Brain regions with high neural flexibility appear consistent with the core regions supporting cognitive flexibility processing in adults, whereas brain regions governing basic brain functions exhibit lower neural flexibility, demonstrating the emergence of functionally flexible brain during early infancy. Adult brains are functionally flexible, a unique characteristic that is thought to contribute to cognitive flexibility. While tools to assess cognitive flexibility during early infancy are lacking, we aimed to assess the spatiotemporal developmental features of “neural flexibility” during the first 2 y of life. Fifty-two typically developing children 0 to 2 y old were longitudinally imaged up to seven times during natural sleep using resting-state functional MRI. Using a sliding window approach, MR-derived neural flexibility, a quantitative measure of the frequency at which brain regions change their allegiance from one functional module to another during a given time period, was used to evaluate the temporal emergence of neural flexibility during early infancy. Results showed that neural flexibility of whole brain, motor, and high-order brain functional networks/regions increased significantly with age, while visual regions exhibited a temporally stable pattern, suggesting spatially and temporally nonuniform developmental features of neural flexibility. Additionally, the neural flexibility of the primary visual network at 3 mo of age was significantly and negatively associated with cognitive ability evaluated at 5/6 y of age. The “flexible club,” comprising brain regions with neural flexibility significantly higher than whole-brain neural flexibility, were consistent with brain regions known to govern cognitive flexibility in adults and exhibited unique characteristics when compared to the functional hub and diverse club regions. Thus, MR-derived neural flexibility has the potential to reveal the underlying neural substrates for developing a cognitively flexible brain during early infancy.