Abstract

Infants born extremely preterm are at risk for compromised cognitive and motor outcome. There are various possibilities as to why this occurs. The "two-hit" hypothesis consists of interrelated developmental disruptions and insults. Both specifically affect the transient subplate neuronal layer (SNL) and the early development of brain circuitry. The SNL, analogous to a switchboard, is critical in connecting cortical and lower brain centers and is highly susceptible to disruptions and insults, producing dysfunctional neural networks. Damage to the SNL provides the putative link between atypical early brain development and later cognitive and academic function that require complex neural circuitry. This, in turn, has major ramifications for developmental assessment and prediction. KEY POINTS: · Preterm brains are highly susceptible to disruptions and insults, this being the two-hit hypothesis.. · There is a variation in which low-grade stressors "sensitize" the infant increasing susceptibility to a second stressor-causing brain damage.. · Subplate neuronal layer damage compromises outcome by interfering with thalamocortical connections.. · Combining neuroimaging and developmental testing is the best way to gain insight into these processes.. · Atypical early brain development may not be evident until the network is mature and challenged..

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