title: 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.
authors: Department of Pediatric Radiology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, CA, USA ; Department of Radiology and Bioinformatics, University of Pittsburgh, Pittsburgh, CA, USA ; Department of Radiology, Children's Hospital Los Angeles, CA, USA ; Brain and Creativity Institute, University of Southern California, CA, USA.
authors: Ashok
authors: A
authors: Panigrahy
authors: Department of Pediatric Radiology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, CA, USA.
authors: Vincent J
authors: VJ
authors: Schmithorst
authors: Department of Pediatric Radiology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, CA, USA ; Department of Radiology, Children's Hospital Los Angeles, CA, USA ; Brain and Creativity Institute, University of Southern California, CA, USA.
authors: Jessica L
authors: JL
authors: Wisnowski
authors: Department of Neurology, Boston Children's Hospital, Boston, MA, USA ; Graduate Program for Neuroscience, Boston University, Boston, MA, USA.
authors: Christopher G
authors: CG
authors: Watson
authors: Department of Neurology, Boston Children's Hospital, Boston, MA, USA.
authors: David C
authors: DC
authors: Bellinger
authors: Department of Cardiology, Boston Children's Hospital, Boston, MA, USA ; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
authors: Jane W
authors: JW
authors: Newburger
authors: Department of Neurology, Boston Children's Hospital, Boston, MA, USA ; Department of Psychiatry, Boston Children's Hospital, Boston, MA, USA ; Department of Radiology, Boston Children's Hospital, Boston, MA, USA ; Department of Neurology, Harvard Medical School, Boston, MA, USA.
authors: Michael J
authors: MJ
authors: Rivkin
mesh_terms: D001921:Brain / Q000503:physiopathology*; D003072:Cognition Disorders / Q000209:etiology* / Q000503:physiopathology*; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D009483:Neuropsychological Tests; D014188:Transposition of Great Vessels / Q000150:complications* / Q000601:surgery; D066127:White Matter / Q000503:physiopathology*
keywords: Brain; Fractional anisotropy; MRI; Neurodevelopment; d-TGA