Deciphering multiway multiscale brain network connectivity from birth to 6 months

Converging evidence suggests that understanding the human brain requires more than just examining pairwise functional brain interactions. The human brain is a complex, nonlinear system, and focusing solely on linear pairwise functional connectivity often overlooks important nonlinear and higher-order interactions. Infancy is a critical period marked by significant brain development that could contribute to future learning, health, and life success. Exploring higher-order functional relationships in the brain can provide insight into brain function and development. To the best of our knowledge, there is no existing research on multiway, multiscale brain network interactions in infants. In this study, we comprehensively investigate the interactions among brain intrinsic connectivity networks (ICNs), including both pairwise (pair-FNC) and triple relationships (tri-FNC). We focused on a dataset of typically developing infants scanned during the first six months of life-a critical period for brain maturation. In total, 71 infants (aged 4-179 days) contributed 126 scans (76 from 41 males, 50 from 30 females). Our results revealed significant hierarchical, multiway, multiscale brain functional network interactions in the infant brain. These findings suggest that tri-FNC provide additional insights beyond what pairwise interactions reveal during early brain development. The tri-FNC predominantly involve the default mode, sensorimotor, visual, limbic, language, salience, and central executive domains. Notably, these triplet networks align with the classical triple network model of the human brain, which includes the default mode network, the salience network, and the central executive network. This suggests that the brain network system might already be initially established during the first six months of infancy. We also found that pair-FNC were less effective at detecting these networks. The present study suggests that exploring tri-FNC can offer additional insights beyond pair-FNC by capturing higher-order nonlinear interactions, potentially yielding more reliable biomarkers to characterize developmental trajectories.