Prefrontal cortex development following variations in early life experience: Cognitive and neural correlates

Abstract

Human brain development is not linear. Prefrontal cortex, typically considered a “late- developing” brain region, undergoes its most rapid development over the first years of life. Early and extended sensitivity of prefrontal cortical circuits to the environment allows maximum potential for infants to benefit from positive experiences, but can become a risk factor if the environment is non-optimal. The goal of the current studies was to characterize the dynamic influence of early experience on the development of prefrontal cortex structure, function, and dependent behaviors across developmental. We examined concurrent and long-term correlates of early risk in two different populations of children: children born moderate-to-late preterm (PT; 32-36 weeks gestation) and children adopted from orphanage care prior to five years of age (post-institutionalized or PI children). In Study 1 we characterized the structure of higher-level, prefrontal- dependent cognitive skills in 9-month-old infants and described the behavioral correlates of exposure to early biological risk (moderate-to-late PT birth) and of normative variations in the familial environment. In Study 2 we examined prefrontal cortex development in adolescents born moderate-to-late PT using structural and functional neuroimaging measures. In Study 3 we documented impacts of early deprivation on the connectivity of frontal-lobe systems in adolescents adopted from early orphanage care. Across studies, we found evidence that early adversity shapes both concurrent and long- term prefrontal cortex development. In healthy, moderate-to-late preterm infants, lower gestational age at birth was associated with poorer performance on five of six early executive function tasks (Study 1a), perhaps driven by underlying differences in early attention shifting skills (Study 1b). Adolescents born moderate-to-late PT had reduced prefrontal cortex volume and altered prefrontal functional activity during an executive function task in comparison to full-term controls (Study 2), suggesting developmental continuity in atypical prefrontal cortex development following moderate-to-late PT birth. Impacts of early orphanage rearing on prefrontal systems were also not fully ameliorated by adolescence. PI youth had reduced cortical white matter volume and poorer white matter microstructural integrity across the brain, including in fronto-limbic and fronto- striatal tracts. These findings highlight the plasticity and vulnerability of prefrontal circuits during the first years of life.