The neonatal brain at rest: A systematic review of task-free functional connectivity in the first 100 days

Over the first 100 days post-partum human brain functions may undergo rapid changes, with plasticity peaking. Studies of task-free functional connectivity (FC) during this period provide a window into early brain organization. Despite growing interest, no systematic review has synthesized findings specifically from this period. We address this gap by reviewing 103 studies examining FC in the neonate brain at rest. Summarised evidence indicates a remarkable degree of both specificity and individual variability in brain function. Neonatal networks exhibit small-world topology with strong local clustering and emerging long-range integration. Sensorimotor, visual, and auditory networks form robust interconnected hubs, supported by structure-function coupling via local myelination and subcortical scaffolding. Early development involves strengthening interhemispheric and long-range connections and increasing network modularity. Higher-order networks (default mode, frontoparietal, salience) are identifiable but less segregated, reflecting their reliance on pathways that are still developing structurally and functionally. Despite these group-level patterns, substantial interindividual variability exists, shaped by both infant- and context-related influences. We discuss these findings within frameworks of Interactive Specialization and experience-dependent learning. We propose that early FC provides intrinsic pre-training for learning and that structure and function co-develop through reciprocal interactions shaped by coordinated activity across subcortical and cortical networks, and early experiences. Adopting a perspective in which intrinsic FC, structural changes, and environmental influences are deeply intertwined, we highlight the need for multimodal longitudinal studies to clarify how such coupled processes shape later developmental trajectories.