Organizational topology of brain and its relationship to ADHD in adolescents with d‐transposition of the great arteries
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Objective: Little 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. Methods: We 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). Results: Changes 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. Conclusion: Our 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.
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In adolescents who had repair of transposition of the great arteries in infancy, disrupted structural network organization is associated with a higher risk of attention deficit disorder and cognitive dysfunction.
“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 65 and cognitive dysfunction.66”
From Neuroimaging, cardiovascular physiology, and functional outcomes in infants with congenital heart disease (2017) · cites this paper as [65]
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Self-citationLong-Term Neurodevelopmental Outcomes After Repair of Cyanotic Congenital Heart Disease
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Marshall, M., Demianczyk, A. C., Rao, R., Wray, J., & Marino, B. S. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-11851-7.00082-3
- Authors
- Schmithorst, V. J., Panigrahy, A., Gaynor, J. W., Watson, C. G., Lee, V., Bellinger, D. C., Rivkin, M. J., & Newburger, J. W.
- Affiliations
- Children's Hospital of Pittsburgh (US)
- University of Southern California (US)
- Children's Hospital of Philadelphia (US)
- Boston University (US)
- Boston Children's Hospital (US)
- Corresponding author
- Panigrahy, Ashok
- ORCID
- Venue
- Brain and Behavior
- Publisher
- Wiley
- Published
- 2016-06-09
- Volume
- 6
- Issue
- 8
- Pages
- e00504-e00504
- ISSN
- 2157-9032 (ISSN-L)
- 2162-3279
- PMC
- PMC4980474
- OpenAlex
- W2409238915
- Cited by
- 46
- References
- 40
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 7 · 2023: 10 · 2022: 5 · 2021: 5 · 2020: 3 · 2019: 2 · 2018: 5 · 2017: 3 · 2016: 1
- FWCI
- 2.33
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Brain and Behavior (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- National Heart, Lung, and Blood Institute (RO1 HL77681)
- Children's Heart Foundation
- National Institute of Neurological Disorders and Stroke (K23063371)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Epidemiology › Congenital Heart Disease Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Keywords
- d-transposition of the great arteries, congenital heart disease, attention deficit hyperactivity disorder, adolescents, arterial switch operation, large-scale brain networks, APOE genotype, APOE ε4, APOE ε2, network integration and segregation, neurobehavioral outcomes, mediation analysis
- MeSH terms
- Adolescent, Attention Deficit Disorder with Hyperactivity, Brain, Female, Humans, Male, Nerve Net, Transposition of Great Vessels, Apolipoprotein E4, Apolipoprotein E2, Diffusion Tensor Imaging
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