Resting-state functional connectivity alterations and neurodevelopmental outcomes in neonates at high risk of hypoxic-ischemic brain injury.

Background

High risk of hypoxic-ischemic brain injury during the neonatal period may disrupt early brain maturation, yet its impact on large-scale functional network organization and later neurodevelopment remains insufficiently understood.

Methods

Resting-state functional near-infrared spectroscopy (fNIRS) was used to characterize cortical functional connectivity in neonates at high risk of hypoxic-ischemic brain injury and controls. Functional connectivity, multivariate pattern analysis, and graph-theoretical approaches were applied to examine group differences in network organization and their associations with developmental outcome.

Results

Compared with controls, high-risk neonates showed reduced functional connectivity predominantly within the frontoparietal network. Seed-based multivariate pattern analysis identified the left parietal lobe as the strongest discriminator between groups. Within the frontoparietal subnetwork, the high-risk group showed reduced clustering coefficient and increased global efficiency, suggesting reduced local segregation and atypical network reorganization. Clustering coefficient was positively associated with later Ages and Stages Questionnaire (ASQ-3) scores in both groups, consistent with a general developmental relationship. In contrast, higher global efficiency and lower nodal clustering in the left prefrontal cortex were associated with poorer developmental outcomes only in the high-risk group.

Conclusions

Neonates at high risk of hypoxic-ischemic brain injury show early alterations in frontoparietal functional organization, some of which are associated with later neurodevelopment. Resting-state fNIRS-derived connectomic measures may therefore have potential for early risk characterization, although further validation in larger independent cohorts is needed.