Hidden Rhythms of a Developing Brain: Multimetric rs-fMRI Insights Into Typical Youth Maturation

Understanding functional brain development during childhood and adolescence is essential for identifying typical neurodevelopmental trajectories. While resting-state fMRI (rs-fMRI) has become a key tool in developmental neuroscience, few studies have jointly examined multiple functional metrics to comprehensively characterize typical brain maturation across youth. We analyzed rs-fMRI data from 395 neurotypical participants aged 6–20 years from the ABIDE I and II datasets. Voxel-wise analyses were conducted using three complementary rs-fMRI metrics: fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity (ReHo), and voxel-mirrored homotopic connectivity (VMHC). Data were harmonized across sites using ComBat and CovBat methods implemented in DPABI to minimize scanner-related variability. Correlation analyses and ANOVA/ANCOVAs were performed to examine developmental age effects. Our results revealed a general pattern of declining local and interhemispheric connectivity with increasing age, across all measures. fALFF decreases were most pronounced in the medial orbitofrontal, caudate, medial occipital cortex, and cerebellum (peak r = −0.210); ReHo showed reductions in the insula and caudate (peak r = −0.169); and VMHC declines were observed in the putamen, cerebellum, superior parietal lobules, and caudate (peak r range = −0.206 to −0.187). These findings outline a developmental trajectory characterized by increasing functional integration and network specialization from late childhood through adolescence. The combined use of fALFF, ReHo, and VMHC provides a robust multitechnical framework for characterizing typical brain development and offers a valuable benchmark for identifying developmental deviations in clinical populations.