Organizational topology of brain and its relationship to ADHD in adolescents with d‐transposition of the great arteries

Abstract

ObjectiveLittle is currently known about the impact of congenital heart disease (CHD) on the organization of large‐scale brain networks in relation to neurobehavioral outcome. We investigated whether CHD might impact ADHD symptoms via changes in brain structural network topology in a cohort of adolescents with d‐transposition of the great arteries (d‐TGA) repaired with the arterial switch operation in early infancy and referent subjects. We also explored whether these effects might be modified by apolipoprotein E (APOE) genotype, as the APOE ε2 allele has been associated with worse neurodevelopmental outcomes after repair of d‐TGA in infancy.MethodsWe applied graph analysis techniques to diffusion tensor imaging (DTI) data obtained from 47 d‐TGA adolescents and 29 healthy referents to construct measures of structural topology at the global and regional levels. We developed statistical mediation models revealing the respective contributions of d‐TGA, APOE genotype, and structural network topology on ADHD outcome as measured by the Connors ADHD/DSM‐IV Scales (CADS).ResultsChanges in overall network connectivity, integration, and segregation mediated worse ADHD outcomes in d‐TGA patients compared to healthy referents; these changes were predominantly in the left and right intrahemispheric regional subnetworks. Exploratory analysis revealed that network topology also mediated detrimental effects of the APOE ε4 allele but improved neurobehavioral outcomes for the APOE ε2 allele.ConclusionOur results suggest that disruption of organization of large‐scale networks may contribute to neurobehavioral dysfunction in adolescents with CHD and that this effect may interact with APOE genotype.

Structural brain abnormalities in adolescents and young adults with congenital heart defect: a systematic review

“…Increased small‐worldness was associated with lower intelligence and poorer reading, math, and executive function . Finally, increased cost and transitivity were associated with hyperactivity and impaired attention …”

“…Among these eight studies, six also had a larger proportion of males in the group with CHD than in the comparison group. In addition, ages between the CHD and comparison groups were significantly different in seven studies: in two, those with CHD were younger than comparison individuals; in five they were older. Exploratory analyses were conducted in seven studies, thus presenting a risk of bias due to possible selective reporting of the results.…”

“…The two graph theory studies explored different cognitive outcomes in the same sample of adolescents and young adults with d‐TGA . Decreased global efficiency was associated with lower IQ, memory, visuospatial skills, lower attention, and hyperactivity . Increased modularity was associated with lower scores on tests of executive function, intelligence, and mathematical ability .…”

Neuroimaging, cardiovascular physiology, and functional outcomes in infants with congenital heart disease

“…To date, there have been no reported structural or functional network‐based studies on the fetal or neonatal brain in CHD. However, in adolescents who had undergone repair of TGA in infancy, disrupted structural network organization was associated with a higher risk of attention deficit disorder and cognitive dysfunction . Both adolescents and adults who underwent surgery for CHD displayed altered functional activity during working memory tests compared with controls .…”

Factors Influencing Neurodevelopment after Cardiac Surgery during Infancy

“…Diminished white matter microstructure may contribute to cognitive compromise in adolescents who underwent open-heart surgery in infancy. Recently, special brain MRI investigations have suggested that disorganization of neuronal networks may contribute to increased attention deficiency hyperactivity disease symptoms in adolescents with TGA (56). …”