White matter functional networks in the developing brain

Authors: HUANG, YALI - University Arkansas For Medical Sciences (UAMS); GLASIER, CHARLES - University Arkansas For Medical Sciences (UAMS); NA, XIAOXU - University Arkansas For Medical Sciences (UAMS); OU, XIAWEI - University Arkansas For Medical Sciences (UAMS)

Submitted to: Frontiers in Neuroscience
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/14/2025
Publication Date: 10/23/2025
Citation: Huang, Y., Glasier, C.M., Na, X., Ou, X. 2025. White matter functional networks in the developing brain. Frontiers in Neuroscience. 18(2025):1-9. https://doi.org/10.3389/fnins.2024.1467446.
DOI: https://doi.org/10.3389/fnins.2024.1467446

Interpretive Summary: fMRI is a commonly used tool for studying brain activity. Research has shown that the functional networks in gray matter undergo many changes from the neonatal stage to childhood, helping children rapidly develop cognitive abilities. However, the functional networks in white matter have not been studied until recently due to weaker signal strength, and the changes in white matter during brain development remain unclear. We aim to compare the white matter functional networks of neonates and 8-year-old children to see how they change during brain development.We conducted fMRI scans on 69 healthy neonates and 38 healthy 8-year-old children and analyzed their brain white matter functional networks. We used a special method to extract white matter networks and studied the characteristics of these networks from both time and frequency perspectives, such as intra-network connectivity, inter-network connectivity, and the frequency characteristics of brain activity. Finally, we compared the differences between the two groups. Additionally, we examined gray matter functional networks for comparison with existing research.We found that the white matter functional networks of neonates and 8-year-old children are different. In 8-year-olds, intra-network connectivity in the optic radiation, corticospinal tract, and anterior corona radiata was weaker than in neonates (p < 0.05), but inter-network connectivity between the cerebral peduncle and anterior corona radiata was stronger (p < 0.05). Furthermore, brain activity in 8-year-olds was more concentrated in the higher frequency range. Overall, the white matter functional networks of the two groups showed significant developmental differences, including increased inter-network connectivity, decreased intra-network connectivity, and an increase in high-frequency activity. Similar changes were also observed in gray matter networks.We were able to reliably measure white matter functional networks in the developing brain, and these differences reflect functional changes and integration during brain development. These findings provide better insights into the role of white matter in brain development.

Technical Abstract: Background: Functional magnetic resonance imaging (fMRI) is widely used to depict neural activity and understand human brain function. Studies show that functional networks in gray matter undergo complex transformations from neonatal age to childhood, supporting rapid cognitive development. However, white matter functional networks, given the much weaker fMRI signal, have not been characterized until recently, and changes in white matter functional networks in the developing brain remain unclear. Purpose: Aims to examine and compare white matter functional networks in neonates and 8-year-old children. Methods: We acquired resting-state fMRI data on 69 full-term healthy neonates and 38 healthy 8-year-old children using a same imaging protocol and studied their brain white matter functional networks using a similar pipeline. First, we utilized the ICA method to extract white matter functional networks. Next, we analyzed the characteristics of the white matter functional networks from both time-domain and frequency-domain perspectives, specifically, intra-network functional connectivity (intra-network FC), inter-network functional connectivity (inter-network FC), and fractional amplitude of low-frequency fluctuation (fALFF). Finally, the differences in the above functional networks’ characteristics between the two groups were evaluated. As a supplemental measure and to confirm with literature findings on gray matter functional network changes in the developing brain, we also studied and reported functional networks in gray matter. Results: White matter functional networks in the developing brain can be depicted for both the neonates and the 8-year-old children. White matter intra-network FC within the optic radiations, corticospinal tract, and anterior corona radiata was lower in 8-year-old children compared to neonates (p < 0.05). Inter-network FC between cerebral peduncle and anterior corona radiation was higher in 8-year-olds (p < 0.05). Additionally, 8-year-olds showed a greater distribution of brain activity energy in the high-frequency range of 0.01-0.15 Hz. Significant developmental differences in brain white matter functional networks exist between the two group, characterized by increased inter-network FC, decreased intra-network FC, and higher high-frequency energy distribution. Similar findings were also observed in gray matter functional networks. Conclusion: White matter functional networks can be reliably measured in the developing brain, and the differences in these networks reflect functional differentiation and integration in brain development.