Alterations in EEG functional connectivity in preterm infants: A systematic review

Objective

To synthesise current evidence on electroencephalography-based functional connectivity in preterm infants and clarify how prematurity alters early brain-network maturation.

Methods

A PRISMA-guided search (PubMed and Web of Science, inception–Mar 2025) identified 24 studies that quantified resting-state functional connectivity or graph-theory metrics in infants born <37 weeks' gestation. Study quality was rated with a six-item electroencephalography-functional connectivity checklist (reference montage, epoch length/number, artefact rejection, volume-conduction control, multiple-comparison correction).

Results

Across studies, neonatal functional connectivity development showed patterns that varied by frequency band, postmenstrual age, and behavioural state. Reported trends included decreasing delta-band coherence with advancing postmenstrual age, increasing frontal theta synchrony, and sleep-state differences in which active sleep more often featured focal high-frequency coupling, whereas quiet sleep involved broader low-frequency integration. Some longitudinal and follow-up studies suggested beta-band connectivity alterations and changes in network topology that may persist into adolescence or adulthood. Graph-theoretical analyses generally described a shift from neonatal small-world organization toward greater segregation, although preterm groups in several studies showed higher clustering and lower efficiency than controls. Methodological heterogeneity was notable, with only one study fulfilling all quality criteria; common limitations included low-density montages (≤ 32 channels) and lack of multiple-comparison control.

Conclusions

Prematurity induces lasting alterations in segregation–integration balance and frequency-specific coupling that relate to later cognitive and motor outcomes. Methodological heterogeneity and small samples, however, limit cross-study comparability.