Neonatal frontal-limbic connectivity is associated with externalizing behaviours in toddlers with Congenital Heart Disease

Alexandra Bonthrone; Andrew Chew; Megan Ní Bhroin; Francesca  Morassutti Rech; Christopher Kelly; Daan Christiaens; Maximilian Pietsch; Jacques-Donald Tournier; Lucilio Cordero-Grande; Anthony Price; Alexia Egloff Collado; Jo Hajnal; Kuberan Pushparajah; John Simpson; David Edwards; Mary Rutherford; Chiara Nosarti; Dafnis Batalle; Serena Counsell

doi:10.1016/j.nicl.2022.103153

Neonatal frontal-limbic connectivity is associated with externalizing behaviours in toddlers with Congenital Heart Disease

Alexandra Bonthrone, Andrew Chew, Megan Ní Bhroin, Francesca Morassutti Rech, Christopher Kelly, Daan Christiaens, Maximilian Pietsch, Jacques-Donald Tournier, Lucilio Cordero-Grande, Anthony Price, Alexia Egloff Collado, Jo Hajnal, Kuberan Pushparajah, John Simpson, David Edwards, Mary Rutherford, Chiara Nosarti, Dafnis Batalle, Serena Counsell

Centre for the Developing Brain; School of Imaging Sciences & Biomedical Engineering; King's College London; London UK
Centre for the Developing Brain, Kings College, St Thomas Campus, London, United Kingdom.
King's College London; Guy's & St Thomas' NHS Foundation Trust

Research output: Contribution to journal › Article › peer-review

5 Citations (Scopus)

Abstract

Children with Congenital Heart Disease (CHD) are at increased risk of neurodevelopmental impairments. The neonatal antecedents of impaired behavioural development are unknown. 43 infants with CHD underwent presurgical brain diffusion-weighted MRI [postmenstrual age at scan median (IQR) = 39.29 (38.71–39.71) weeks] and a follow-up assessment at median age of 22.1 (IQR 22.0–22.7) months in which parents reported internalizing and externalizing problem scores on the Child Behaviour Checklist. We constructed structural brain networks from diffusion-weighted MRI and calculated edge-wise structural connectivity as well as global and local brain network features. We also calculated presurgical cerebral oxygen delivery, and extracted perioperative variables, socioeconomic status at birth and a measure of cognitively stimulating parenting. Lower degree in the right inferior frontal gyrus (partial ρ = −0.687, p < 0.001) and reduced connectivity in a frontal-limbic sub-network including the right inferior frontal gyrus were associated with higher externalizing problem scores. Externalizing problem scores were unrelated to neonatal clinical course or home environment. However, higher internalizing problem scores were associated with earlier surgery in the neonatal period (partial ρ = −0.538, p = 0.014). Our results highlight the importance of frontal-limbic networks to the development of externalizing behaviours and provide new insights into early antecedents of behavioural impairments in CHD.

Original language	English
Article number	103153
Journal	NeuroImage: Clinical
Volume	36
DOIs	https://doi.org/10.1016/j.nicl.2022.103153
Publication status	Published - 17 Aug 2022

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Bonthrone, A., Chew, A., Ní Bhroin, M., Morassutti Rech, F., Kelly, C., Christiaens, D., Pietsch, M., Tournier, J.-D., Cordero-Grande, L., Price, A., Egloff Collado, A., Hajnal, J., Pushparajah, K., Simpson, J., Edwards, D., Rutherford, M., Nosarti, C., Batalle, D., & Counsell, S. (2022). Neonatal frontal-limbic connectivity is associated with externalizing behaviours in toddlers with Congenital Heart Disease. NeuroImage: Clinical, 36, Article 103153. https://doi.org/10.1016/j.nicl.2022.103153

@article{f0dbd3d9cdc14d5f999224c88d2d34a3,

title = "Neonatal frontal-limbic connectivity is associated with externalizing behaviours in toddlers with Congenital Heart Disease",

abstract = "Children with Congenital Heart Disease (CHD) are at increased risk of neurodevelopmental impairments. The neonatal antecedents of impaired behavioural development are unknown. 43 infants with CHD underwent presurgical brain diffusion-weighted MRI [postmenstrual age at scan median (IQR) = 39.29 (38.71–39.71) weeks] and a follow-up assessment at median age of 22.1 (IQR 22.0–22.7) months in which parents reported internalizing and externalizing problem scores on the Child Behaviour Checklist. We constructed structural brain networks from diffusion-weighted MRI and calculated edge-wise structural connectivity as well as global and local brain network features. We also calculated presurgical cerebral oxygen delivery, and extracted perioperative variables, socioeconomic status at birth and a measure of cognitively stimulating parenting. Lower degree in the right inferior frontal gyrus (partial ρ = −0.687, p < 0.001) and reduced connectivity in a frontal-limbic sub-network including the right inferior frontal gyrus were associated with higher externalizing problem scores. Externalizing problem scores were unrelated to neonatal clinical course or home environment. However, higher internalizing problem scores were associated with earlier surgery in the neonatal period (partial ρ = −0.538, p = 0.014). Our results highlight the importance of frontal-limbic networks to the development of externalizing behaviours and provide new insights into early antecedents of behavioural impairments in CHD.",

author = "Alexandra Bonthrone and Andrew Chew and {N{\'i} Bhroin}, Megan and {Morassutti Rech}, Francesca and Christopher Kelly and Daan Christiaens and Maximilian Pietsch and Jacques-Donald Tournier and Lucilio Cordero-Grande and Anthony Price and {Egloff Collado}, Alexia and Jo Hajnal and Kuberan Pushparajah and John Simpson and David Edwards and Mary Rutherford and Chiara Nosarti and Dafnis Batalle and Serena Counsell",

note = "Funding Information: This work was funded the Medical Research Council UK (MR/L011530/1 and MR/V002465/1), the British Heart Foundation (FS/15/55/31649), and Action Medical Research (GN2630). This research was supported by core funding from the Wellcome/EPSRC Centre for Medical Engineering (WT 203148/Z/16/Z), MRC strategic grant (MR/K006355/1), Medical Research Council Centre grant (MR/N026063/1), and by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy{\textquoteright}s and St Thomas{\textquoteright} NHS Foundation Trust and King{\textquoteright}s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and social care. DC is supported by the Flemish Research Foundation (FWO; grant number 12ZV420N). MP is funded in part by the Bill & Melinda Gates Foundation (INV-005774). LCG is supported by the Comunidad de Madrid-Spain (Support for R&D Projects; BGP18/00178). Funding Information: We would like to thank the families who participated in this study. We also thank our research radiologists, including Sophie Arulkumaran and Kelly Pegoretti; our research radiographers: Emer Hughes, Joanna Allsop, Elaine Green, Louise Dillon and Kathleen Colford; and our neonatal scanning team including Jennifer Almalbis, Jessica Kimpton, Camilla O'Keeffe and Jacqueline Brandon. In addition, we thank the staff from the St Thomas{\textquoteright} Neonatal Intensive Care Unit, the Evelina London Children's Hospital Fetal and Paediatric Cardiology Departments, the Evelina London Paediatric Intensive Care Unit and the Centre for the Developing Brain at King's College London. This work was funded the Medical Research Council UK (MR/L011530/1 and MR/V002465/1), the British Heart Foundation (FS/15/55/31649), and Action Medical Research (GN2630). This research was supported by core funding from the Wellcome/EPSRC Centre for Medical Engineering (WT 203148/Z/16/Z), MRC strategic grant (MR/K006355/1), Medical Research Council Centre grant (MR/N026063/1), and by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas{\textquoteright} NHS Foundation Trust and King's College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and social care. DC is supported by the Flemish Research Foundation (FWO; grant number 12ZV420N). MP is funded in part by the Bill & Melinda Gates Foundation (INV-005774). LCG is supported by the Comunidad de Madrid-Spain (Support for R&D Projects; BGP18/00178). Publisher Copyright: {\textcopyright} 2022 The Author(s)",

year = "2022",

month = aug,

day = "17",

doi = "10.1016/j.nicl.2022.103153",

language = "English",

volume = "36",

journal = "NeuroImage: Clinical",

issn = "2213-1582",

publisher = "Elsevier",

}

Bonthrone, A , Chew, A, Ní Bhroin, M, Morassutti Rech, F, Kelly, C , Christiaens, D , Pietsch, M , Tournier, J-D , Cordero-Grande, L , Price, A , Egloff Collado, A , Hajnal, J , Pushparajah, K, Simpson, J, Edwards, D , Rutherford, M , Nosarti, C , Batalle, D & Counsell, S 2022, 'Neonatal frontal-limbic connectivity is associated with externalizing behaviours in toddlers with Congenital Heart Disease', NeuroImage: Clinical, vol. 36, 103153. https://doi.org/10.1016/j.nicl.2022.103153

TY - JOUR

T1 - Neonatal frontal-limbic connectivity is associated with externalizing behaviours in toddlers with Congenital Heart Disease

AU - Bonthrone, Alexandra

AU - Chew, Andrew

AU - Ní Bhroin, Megan

AU - Morassutti Rech, Francesca

AU - Kelly, Christopher

AU - Christiaens, Daan

AU - Pietsch, Maximilian

AU - Tournier, Jacques-Donald

AU - Cordero-Grande, Lucilio

AU - Price, Anthony

AU - Egloff Collado, Alexia

AU - Hajnal, Jo

AU - Pushparajah, Kuberan

AU - Simpson, John

AU - Edwards, David

AU - Rutherford, Mary

AU - Nosarti, Chiara

AU - Batalle, Dafnis

AU - Counsell, Serena

N1 - Funding Information: This work was funded the Medical Research Council UK (MR/L011530/1 and MR/V002465/1), the British Heart Foundation (FS/15/55/31649), and Action Medical Research (GN2630). This research was supported by core funding from the Wellcome/EPSRC Centre for Medical Engineering (WT 203148/Z/16/Z), MRC strategic grant (MR/K006355/1), Medical Research Council Centre grant (MR/N026063/1), and by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and social care. DC is supported by the Flemish Research Foundation (FWO; grant number 12ZV420N). MP is funded in part by the Bill & Melinda Gates Foundation (INV-005774). LCG is supported by the Comunidad de Madrid-Spain (Support for R&D Projects; BGP18/00178). Funding Information: We would like to thank the families who participated in this study. We also thank our research radiologists, including Sophie Arulkumaran and Kelly Pegoretti; our research radiographers: Emer Hughes, Joanna Allsop, Elaine Green, Louise Dillon and Kathleen Colford; and our neonatal scanning team including Jennifer Almalbis, Jessica Kimpton, Camilla O'Keeffe and Jacqueline Brandon. In addition, we thank the staff from the St Thomas’ Neonatal Intensive Care Unit, the Evelina London Children's Hospital Fetal and Paediatric Cardiology Departments, the Evelina London Paediatric Intensive Care Unit and the Centre for the Developing Brain at King's College London. This work was funded the Medical Research Council UK (MR/L011530/1 and MR/V002465/1), the British Heart Foundation (FS/15/55/31649), and Action Medical Research (GN2630). This research was supported by core funding from the Wellcome/EPSRC Centre for Medical Engineering (WT 203148/Z/16/Z), MRC strategic grant (MR/K006355/1), Medical Research Council Centre grant (MR/N026063/1), and by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas’ NHS Foundation Trust and King's College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and social care. DC is supported by the Flemish Research Foundation (FWO; grant number 12ZV420N). MP is funded in part by the Bill & Melinda Gates Foundation (INV-005774). LCG is supported by the Comunidad de Madrid-Spain (Support for R&D Projects; BGP18/00178). Publisher Copyright: © 2022 The Author(s)

PY - 2022/8/17

Y1 - 2022/8/17

N2 - Children with Congenital Heart Disease (CHD) are at increased risk of neurodevelopmental impairments. The neonatal antecedents of impaired behavioural development are unknown. 43 infants with CHD underwent presurgical brain diffusion-weighted MRI [postmenstrual age at scan median (IQR) = 39.29 (38.71–39.71) weeks] and a follow-up assessment at median age of 22.1 (IQR 22.0–22.7) months in which parents reported internalizing and externalizing problem scores on the Child Behaviour Checklist. We constructed structural brain networks from diffusion-weighted MRI and calculated edge-wise structural connectivity as well as global and local brain network features. We also calculated presurgical cerebral oxygen delivery, and extracted perioperative variables, socioeconomic status at birth and a measure of cognitively stimulating parenting. Lower degree in the right inferior frontal gyrus (partial ρ = −0.687, p < 0.001) and reduced connectivity in a frontal-limbic sub-network including the right inferior frontal gyrus were associated with higher externalizing problem scores. Externalizing problem scores were unrelated to neonatal clinical course or home environment. However, higher internalizing problem scores were associated with earlier surgery in the neonatal period (partial ρ = −0.538, p = 0.014). Our results highlight the importance of frontal-limbic networks to the development of externalizing behaviours and provide new insights into early antecedents of behavioural impairments in CHD.

AB - Children with Congenital Heart Disease (CHD) are at increased risk of neurodevelopmental impairments. The neonatal antecedents of impaired behavioural development are unknown. 43 infants with CHD underwent presurgical brain diffusion-weighted MRI [postmenstrual age at scan median (IQR) = 39.29 (38.71–39.71) weeks] and a follow-up assessment at median age of 22.1 (IQR 22.0–22.7) months in which parents reported internalizing and externalizing problem scores on the Child Behaviour Checklist. We constructed structural brain networks from diffusion-weighted MRI and calculated edge-wise structural connectivity as well as global and local brain network features. We also calculated presurgical cerebral oxygen delivery, and extracted perioperative variables, socioeconomic status at birth and a measure of cognitively stimulating parenting. Lower degree in the right inferior frontal gyrus (partial ρ = −0.687, p < 0.001) and reduced connectivity in a frontal-limbic sub-network including the right inferior frontal gyrus were associated with higher externalizing problem scores. Externalizing problem scores were unrelated to neonatal clinical course or home environment. However, higher internalizing problem scores were associated with earlier surgery in the neonatal period (partial ρ = −0.538, p = 0.014). Our results highlight the importance of frontal-limbic networks to the development of externalizing behaviours and provide new insights into early antecedents of behavioural impairments in CHD.

UR - http://www.scopus.com/inward/record.url?scp=85136067858&partnerID=8YFLogxK

U2 - 10.1016/j.nicl.2022.103153

DO - 10.1016/j.nicl.2022.103153

M3 - Article

SN - 2213-1582

VL - 36

JO - NeuroImage: Clinical

JF - NeuroImage: Clinical

M1 - 103153

ER -

Neonatal frontal-limbic connectivity is associated with externalizing behaviours in toddlers with Congenital Heart Disease

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