Associations of behavioral problems with white matter circuits connecting to the frontal lobes in school-aged children born at term and preterm.

Introduction: This study investigated whether internalizing and externalizing behavioral problems in children were associated with fractional anisotropy of white matter tracts connecting other brain regions to the frontal lobes. We contrasted patterns of association between children born at term (FT) and very preterm (PT: gestational age at birth =< 32 weeks). Methods: Parents completed the Child Behavior Checklist/6-18 questionnaire to quantify behavioral problems when their children were age 8 years (N = 36 FT and 37 PT). Diffusion magnetic resonance scans were collected at the same age and analyzed using probabilistic tractography. Multiple linear regressions investigated the strength of association between age-adjusted T-scores of internalizing and externalizing problems and mean fractional anisotropy (mean-FA) of right and left uncinate, arcuate, anterior thalamic radiations, and dorsal cingulate bundle, controlling for birth group and sex. Results: Models predicting internalizing T-scores found significant group-by-tract interactions for left and right arcuate and right uncinate. Internalizing scores were negatively associated with mean-FA of left and right arcuate only in FT children (p left AF = 0.01, p right AF = 0.01). Models predicting externalizing T-scores found significant group-by-tract interactions for the left arcuate and right uncinate. Externalizing scores were negatively associated with mean-FA of right uncinate in FT (p right UF = 0.01) and positively associated in PT children (p right UF preterm = 0.01). Other models were not significant. Conclusions: In children with a full range of scores on behavioral problems from normal to significantly elevated, internalizing and externalizing behavioral problems were negatively associated with mean-FA of white matter tracts connecting to frontal lobes in FT children; externalizing behavioral problems were positively associated with mean-FA of the right uncinate in PT children. The different associations by birth group suggest that the neurobiology of behavioral problems differs in the two birth groups.

Associations of behavioral problems with white matter circuits connecting to the frontal lobes in school-aged children born at term and preterm.

Introduction: This study investigated whether behavioral problems in children were associated with fractional anisotropy (FA) of white matter tracts connecting from other brain regions to right and left frontal lobes. We considered internalizing and externalizing behavioral problems separately and contrasted patterns of associations in children born at term and very preterm. Methods: Parents completed the Child Behavior Checklist/6-18 questionnaire to quantify behavioral problems when their children were age 8 years (N=36 FT and 37 PT). Diffusion magnetic resonance scans were collected at the same age and analyzed using probabilistic tractography. We used multiple linear regression to investigate the strength of association between age-adjusted T-scores of internalizing and externalizing problems and mean fractional anisotropy (mean-FA) of right and left uncinate, arcuate, and anterior thalamic radiations, controlling for birth group and sex. Results: Regression models predicting internalizing T-scores from mean-FA found significant group-by-tract interactions for the left and right arcuate and right uncinate. Internalizing scores were negatively associated with mean-FA of left and right arcuate only in children born at term (pleft AF =0.01, pright AF =0.01). Regression models predicting externalizing T-scores from mean-FA found significant group-by-tract interactions for the left arcuate and right uncinate. Externalizing scores were negatively associated with mean-FA of right uncinate in children born at term (pright UF =0.01) and positively associated in children born preterm (pright UF preterm =0.01). Other models were not significant. Conclusions: In this sample of children with scores for behavioral problems across the full range, internalizing and externalizing behavioral problems were negatively associated with mean-FA of white matter tracts connecting to frontal lobes in children born at term; externalizing behavioral problems were positively associated with mean-FA of the right uncinate in children born preterm. The different associations by birth group suggest that the neurobiology of behavioral problems differs in the two birth groups.

Associations of Behavioral Problems and White Matter Properties of the Cerebellar Peduncles in Boys and Girls Born Full Term and Preterm.

Accumulating evidence suggests that the role of cerebellum includes regulation of behaviors; cerebellar impairment may lead to behavioral problems. Behavioral problems differ by sex: internalizing problems are more common in girls, externalizing problems in boys. Behavioral problems are also elevated in children born preterm (PT) compared to children born full term (FT). The current study examined internalizing and externalizing problems in 8-year-old children in relation to sex, birth-group, fractional anisotropy (FA) of the three cerebellar peduncles (superior, middle, and inferior), and interactions among these predictor variables. Participants (N = 78) were 44 boys (28 PT) and 34 girls (15 PT). We assessed behavioral problems via standardized parent reports and FA of the cerebellar peduncles using deterministic tractography. Internalizing problems were higher in children born PT compared to children born FT (p = .032); the interaction of sex and birth-group was significant (p = .044). When considering the contribution of the mean-tract FA of cerebellar peduncles to behavioral problems, there was a significant interaction of sex and mean-tract FA of the inferior cerebellar peduncle (ICP) with internalizing problems; the slope was negative in girls (p = .020) but not in boys. In boys, internalizing problems were only associated with mean-tract FA ICP in those born preterm (p = .010). We found no other significant associations contributing to internalizing or externalizing problems. Thus, we found sexual dimorphism and birth-group differences in the association of white matter metrics of the ICP and internalizing problems in school-aged children. The findings inform theories of the origins of internalizing behavioral problems in middle childhood and may suggest approaches to treatment at school age.