Microstructure of the Dorsal Anterior Cingulum Bundle in Very Preterm Neonates Predicts the Preterm Behavioral Phenotype at 5 Years of Age

Background: The cingulum bundle (CB), specifically the dorsal anterior portion of the CB, plays an important role in psychiatric illnesses; however, its role during early development is unclear. This study investigated whether neonatal white matter microstructure in the CB and its subregions is associated with subsequent preterm behavioral phenotype symptoms (internalizing, inattention, and social deficits) in very preterm (VPT) children. Methods: Diffusion magnetic resonance imaging data were obtained on a 3T scanner in 138 sleeping nonsedated neonates: 55 full-term neonates (gestational age ≥ 36 weeks) and 83 VPT neonates (gestational age < 30 weeks). The CB was tracked using probabilistic tractography and split into anterior and posterior portions. When children were 5 years of age, parents (n = 80) and teachers (n = 63) of VPT children completed questionnaires of preterm behavioral phenotype symptoms. Linear regression models were used to relate measures of neonatal CB microstructure and childhood preterm behavioral phenotype symptoms (n = 56 parent report, n = 45 teacher report). Results: Mean diffusivity in the anterior and posterior CB was increased in VPT neonates compared with full-term neonates. Increased fractional anisotropy and decreased mean diffusivity in the right anterior CB, but not in the posterior CB, were related to increased preterm behavioral phenotype symptoms in VPT children as reported by parents and teachers. Conclusions: Aberrations in the anterior portion of the right CB may underlie the early development of the preterm behavioral phenotype. This finding provides the foundation for future mechanistic and therapeutic investigations into the role of the anterior cingulum in the development of psychopathology in VPT infants.