RS-fMRI Evidence for Differential Within- and Between-Module Interactions Across Age

BackgroundPrevious resting-state functional MRI (rsfMRI) studies have identified a robust inverse relationship between nodal strength and amplitude of low-frequency fluctuations (ALFF) across cortical modules. This study examined whether this negative relationship exists within modules and further explored age-related effects on these associations. MethodsUsing MOSI (modularity analysis and similarity measurements), rsfMRI data from three public datasets spanning different age cohorts were analyzed. Correlations between ALFF and nodal strength between modules or voxel concordance within modules were calculated. Geometric mean p-values assessed robustness at the individual level. ResultsConfirming prior findings, a significant inverse correlation between nodal strength and ALFF was observed at the between-module level (geometric p-values 10-4 to 10-5). Within-module negative associations were nonsignificant in younger cohorts at individual level (mean ages 10 and 21) but became significant in the older cohort (mean age 33). The magnitude of this negative association increased with age, consistent with maturation of local inhibitory network mechanisms. ConclusionsThe findings support MOSI as a valid FP method for cortical network construction, with within-module inhibitory effects strengthening in adulthood. The age-dependent modulation reveals network maturation at the modular level, with implications for neurodevelopmental and neuropsychiatric conditions.