Relationship of white matter network topology and cognitive outcome in adolescents with d-transposition of the great arteries

Abstract

Patients with congenital heart disease (CHD) are at risk for neurocognitive impairments. Little is known about the impact of CHD on the organization of large-scale brain networks. We applied graph analysis techniques to diffusion tensor imaging (DTI) data obtained from 49 adolescents with dextro-transposition of the great arteries (d-TGA) repaired with the arterial switch operation in early infancy and 29 healthy referent adolescents. We examined whether differences in neurocognitive functioning were related to white matter network topology. We developed mediation models revealing the respective contributions of peri-operative variables and network topology on cognitive outcome. Adolescents with d-TGA had reduced global efficiency at a trend level (p = 0.061), increased modularity (p = 0.012), and increased small-worldness (p = 0.026) as compared to controls. Moreover, these network properties mediated neurocognitive differences between the d-TGA and referent adolescents across every domain assessed. Finally, structural network topology mediated the neuroprotective effect of longer duration of core cooling during reparative neonatal cardiac surgery, as well as the detrimental effects of prolonged hospitalization. Taken together, worse neurocognitive function in adolescents with d-TGA is mediated by global differences in white matter network topology, suggesting that disruption of this configuration of large-scale networks drives neurocognitive dysfunction. These data provide new insights into the interplay between perioperative factors, brain organization, and cognition in patients with complex CHD.

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

“…2014) and is mediated by global differences in white matter structural network topology (Panigrahy et al. 2015). These findings suggest that alteration of large‐scale network organization can adversely affect cognitive dysfunction in children with surgically treated CHD.…”

“…The topology differences involving network segregation (transitivity) differed, however, from those (modularity and small‐worldness) found to mediate poorer neurocognitive outcomes (Panigrahy et al. 2015). This suggests that different structural features may underlie cognitive as compared to behavioral deficits such as inattentiveness and hyperactivity in d‐TGA subjects.…”

“…2015). With regard to network segregation, however, transitivity was found to mediate worse ADHD outcome, in contrast to small‐worldness and modularity mediating worse neurocognitive outcome.…”

“…A flow diagram for the construction of WM structural networks from DTI including registration, segmentation, generation of WM fiber tracts using deterministic tractography, and generation of adjacency matrix and nodes (see Panigrahy et al. 2015 for more details).…”

“…A previous publication (Panigrahy et al. 2015) focused on relations between d‐TGA, structural network topology, and neurocognitive outcomes (e.g., WISC‐IQ, WIAT scores, memory tests, etc.) Here we focus on inattentiveness and hyperactivity.…”