The architecture of a human brain does not arrive fully formed — it is assembled under pressure, in the compressed span of early infancy. Understanding precisely how neural networks self-organize during this window has profound implications for identifying developmental risk, explaining individual differences in cognition, and potentially timing interventions for neurodevelopmental conditions.
This systematic review synthesizes 103 studies examining task-free functional connectivity in neonates across the first 100 days of postnatal life — the largest such synthesis for this specific developmental window. The aggregated evidence reveals that even in the earliest weeks, the neonatal brain is far from a blank slate. Resting-state networks display small-world topology, characterized by dense local clustering alongside emerging long-range integration. Sensorimotor, visual, and auditory networks emerge as robust, interconnected hubs, their organization scaffolded by localized myelination and subcortical architecture. Interhemispheric connections and network modularity progressively strengthen across this period. Notably, higher-order networks — the default mode, frontoparietal, and salience networks associated with complex cognition — are detectable but remain poorly segregated, reflecting their dependence on white matter tracts still undergoing structural maturation. Despite these consistent group-level patterns, marked interindividual variability is documented, shaped by both biological and contextual factors.
For the broader neuroscience and developmental health field, this review offers a critical baseline. Most prior work has lumped early infancy into broader developmental categories, obscuring the specificity of this 100-day window. The proposal that early functional connectivity acts as intrinsic pre-training — a kind of neural priming before experience-dependent learning takes hold — reframes passively observed resting-state activity as functionally purposeful. One important limitation is that nearly all contributing studies are observational and cross-sectional, precluding causal interpretation of developmental trajectories. The field also lacks standardized acquisition protocols, which constrains cross-study comparison. Nevertheless, as a consolidating resource for neonatal neuroimaging, this is a genuinely significant contribution that could inform early biomarker research for conditions like autism spectrum disorder and cerebral palsy.