Neuroanatomical subtypes of preterm adolescents

Preterm infants have a higher risk for developing neurocognitive deficits and behavioral abnormalities across the lifespan, but the individual long-term neurobiological heterogeneity presents a challenge for developmental risk assessment and outcome prediction. Thus, we took advantage of the large sample size of the Adolescent Brain Cognitive Development dataset to investigate neuroanatomical subtypes that were previously unobservable in typical case-control designs, and explored potential neurodevelopmental mechanisms by analyzing the brain maturation of preterm subtypes. Our findings revealed two markedly distinct and reproducible brain structural and behavioral features that differentiated subtypes of preterm adolescents: 1) the "at-risk" subtype had an "average preterm brain pattern" of widespread lower cortical volume/area and subcortical volume and higher cortical thickness, and showed cognitive deficiencies and psychopathological risk; 2) the "resilient" subtype demonstrated more complex brain structural differences including both higher and lower cortical and subcortical volumes in different regions simultaneously, as well as widespread higher cortical area and lower cortical thickness. In addition, the "resilient: subtype showed accelerated brain maturation that may contribute to their normal cognitive function though they still had psychopathological risk. These neurodevelopmental alterations had significant associations with gestational age, birth weight, puberty development levels, psychopathological risk and cognitive deficits. The findings provide mechanistic insights into neurobiological heterogeneities in long-term neurodevelopmental trajectories in preterm adolescents, aiming to guide risk stratification and support healthy development in preterm adolescents.