Interplay of brain structure and function in neonatal congenital heart disease
Open accessAbstract
Objective: To evaluate whether structural and microstructural brain abnormalities in neonates with congenital heart disease (CHD) correlate with neuronal network dysfunction measured by analysis of EEG connectivity. Methods: We studied a prospective cohort of 20 neonates with CHD who underwent continuous EEG monitoring before surgery to assess functional brain maturation and network connectivity, structural magnetic resonance imaging (MRI) to determine the presence of brain injury and structural brain development, and diffusion tensor MRI to assess brain microstructural development. Results: Neonates with MRI brain injury and delayed structural and microstructural brain development demonstrated significantly stronger high‐frequency (beta and gamma frequency band) connectivity. Furthermore, neonates with delayed microstructural brain development demonstrated significantly weaker low‐frequency (delta, theta, alpha frequency band) connectivity. Neonates with brain injury also displayed delayed functional maturation of EEG background activity, characterized by greater background discontinuity. Interpretation: These data provide new evidence that early structural and microstructural developmental brain abnormalities can have immediate functional consequences that manifest as characteristic alterations of neuronal network connectivity. Such early perturbations of developing neuronal networks, if sustained, may be responsible for the persistent neurocognitive impairment prevalent in adolescent survivors of CHD. These foundational insights into the complex interplay between evolving brain structure and function may have relevance for a wide spectrum of neurological disorders manifesting early developmental brain injury.
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Lower fractional anisotropy values are associated with altered functional connectivity on electroencephalography before surgery in infants with congenital heart disease, highlighting synchronicity between structural and functional brain development.
“The functional impact of early microstructural abnormalities identified on dMRI in infants with CHD has been highlighted recently in a study showing that lower fractional anisotropy values are associated with altered functional connectivity using electroencephalography before surgery, 60 highlighting the synchronicity between structural and functional brain development.”
From Neuroimaging, cardiovascular physiology, and functional outcomes in infants with congenital heart disease (2017) · cites this paper as [60]
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Ehrler, M., von Rhein, M., Schlosser, L., Brugger, P., Greutmann, M., Kretschmar, O., Latal, B., & Tuura, R. (2021) · NeuroImage Clinical · doi:10.1016/j.nicl.2021.102885 · Cited by 7 · see citing works
de Sousa, T. M. A., Gugelmin, V. S., Fernandes, G. M., Aucélio, C. N., Costa, K. N., & Tristão, R. M. (2019) · Arquivos de Neuro-Psiquiatria · doi:10.1590/0004-282x20190030 · Cited by 5 · see citing works
Boutalbi, N., Dahan, S., Rozalen, W., Beretti, T., Fortis, L., Delefosse, L., Cloarec, R., Testud, B., Fouilloux, V., Gran, C., et al. (2025) · Pediatric Research · doi:10.1038/s41390-025-04437-8 · Cited by 4 · see citing works
Roberts, S. D., Sananes, R., Wojtowicz, M. A., Seed, M., Miller, S. P., Chau, V., Au‐Young, S. H., Guo, T., Ly, L. G., Kazazian, V., et al. (2024) · Cardiology in the Young · doi:10.1017/s1047951123004316 · Cited by 4 · see citing works
Self-citationPrevalence of Ischemic Brain Injury in Neonates With Congenital Heart Disease
Kim, C. S., Chetan, D., Kazazian, V., Alzamil, J., Chau, V., Seed, M., Miller, S. P., & Selvanathan, T. (2026) · Neurology · doi:10.1212/wnl.0000000000214569 · Cited by 2 · see citing works
Self-citationNormal development of the brain: a survey of joint structural–functional brain studies
Namiranian, R., Malakshan, S. R., Moghaddam, H. A., Khadem, A. A., & Jafari, R. (2022) · Reviews in the Neurosciences · doi:10.1515/revneuro-2022-0017 · Cited by 2 · see citing works
(2023) · Cardiology in the Young · doi:10.1017/s1047951123001804 · Cited by 1 · see citing works
Glass, T. J. A., Seed, M., & Chau, V. (2019) · Elsevier eBooks · doi:10.1016/b978-0-323-54392-7.00015-7 · Cited by 1 · see citing works
Self-citationDiagnostic value of neuroimaging techniques in newborn infants with malformations of internal organs
Омаровна, Т. С., Ushakova, L. V., Filippova, E. A., Bychenko, V. G., Dorofeeva, E. I., Александрович, Б. А., & Degtyarev, D. N. (2017) · Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics) · doi:10.21508/1027-4065-2017-2-1-47-52
Fetal Cerebral Consequences of Structural Heart Disease: Can These Be Ameliorated?
Seed, M. (2019) · Cambridge University Press eBooks · doi:10.1017/9781108564434.017
Self-citationLinking congenital heart disease and brain functional connectivity in newborns
Asis‐Cruz, J. D., & Limperopoulos, C. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-817988-8.00024-5
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Spectral EEG in Congenital Heart Disease: A Case–Control Study in Infants Undergoing Cardiac Surgery
Cainelli, E., Simonato, M., Sartori, A., Padalino, M. A., Sartori, S., Ancona, C., Vedovelli, L., Cogo, P. E., & Bisiacchi, P. S. (2025) · Pediatric Cardiology · doi:10.1007/s00246-025-03958-7
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- Authors
- Birca, A., Vakorin, V. A., Porayette, P., Madathil, S., Chau, V., Seed, M., Doesburg, S. M., Blaser, S., Nita, D. A., Sharma, R., Duerden, E. G., Hickey, E. J., Miller, S. P., & Hahn, C. D.
- Affiliations
- University of Toronto (CA)
- Simon Fraser University (CA)
- SickKids Foundation (CA)
- Program in Neurosciences and Mental Health SickKids Research Institute Toronto Canada
- Corresponding author
- Hahn, Cecil D.
- ORCID
- Venue
- Annals of Clinical and Translational Neurology
- Publisher
- Wiley
- Published
- 2016-08-14
- Volume
- 3
- Issue
- 9
- Pages
- 708-722
- ISSN
- 2328-9503 (ISSN-L)
- PMC
- PMC5018583
- OpenAlex
- W2508688961
- Cited by
- 46
- References
- 52
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 3 · 2023: 7 · 2022: 3 · 2021: 4 · 2020: 5 · 2019: 9 · 2018: 2 · 2017: 5 · 2016: 1
- FWCI
- 5.32
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Annals of Clinical and Translational Neurology (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- TSpace (University of Toronto) (submittedVersion, cc-by-nc-nd)
- Scholarship@Western (Western University) (submittedVersion)
- Funders
- Canadian Institutes of Health Research (MOP93780)
- Topics
- Health Sciences › Medicine › Epidemiology › Congenital Heart Disease Studies
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal and fetal brain pathology
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Fetal and Pediatric Neurological Disorders
- Keywords
- congenital heart disease, neonates, EEG connectivity, neuronal network dysfunction, brain injury, brain microstructure, brain development, EEG background activity, neurocognitive impairment, adolescent survivors, structural MRI, diffusion tensor imaging
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