Aberrant brain functional connectivity in newborns with congenital heart disease before cardiac surgery

Asis-Cruz, Josepheen De; Donofrio, Mary T.; Vézina, Gilbert; Limperopoulos, Catherine

doi:10.1016/j.nicl.2017.09.020

Cited by 53 publications

(36 citation statements)

References 58 publications

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“…Opposed to our structural connectomics findings, a previous analysis of the functional connectome demonstrated a preserved functional global network architecture in CHD neonates (De Asis-Cruz et al 2018). This contrast in global topological findings could be partly attributed to the exclusion of CHD neonates with parenchymal brain lesions, but could as well arise from temporal differences in functional and structural network maturation.…”

Section: Reduced Integration and Higher Segregation Of Global And Nodcontrasting

confidence: 76%

Delayed maturation of the structural brain connectome in neonates with congenital heart disease

Feldmann

Guo

Miller

et al. 2020

Preprint

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There is emerging evidence for delayed brain development in neonates with congenital heart disease (CHD). We hypothesize that the perioperative development of the structural brain connectome is a proxy to such delays. Therefore, we set out to quantify the alterations and longitudinal pre- to postoperative changes in the connectome in CHD neonates and assess risk factors for disturbed perioperative network development relative to healthy term newborns. In this prospective cohort study, 114 term neonates with CHD underwent cardiac surgery at the University Children’s Hospital Zurich. Forty-six healthy term newborns were included as controls. Pre- and postoperative structural connectomes were derived from mean fractional anisotropy values of fibre pathways traced using diffusion tractography. Graph theory parameters calculated across a range of proportional cost thresholds were compared between groups by multi-threshold permutation correction adjusting for con-founders. Network based statistic was calculated for edgewise network comparison. White matter injury (WMI) volume was quantified on 3D T1-weighted images. Random coefficient mixed models with interaction terms of (i) CHD subtype and (ii) WMI volume with postmenstrual age at MRI respectively were built to assess modifying effects on network development. Pre- and postoperatively, at the global level, efficiency, indicative of network integration, was higher in controls compared to CHD neonates. In contrast, local efficiency and transitivity, indicative of network segregation, were higher in CHD neonates compared to controls (all p<0.025 for one-sided t-tests). Preoperatively these group differences were also found across multiple widespread nodes (all p<0.025, accounting for multiple comparison), whereas postoperatively nodal differences were not evident. At the edge-level, the majority of weaker connections in CHD neonates compared to controls involved interhemispheric connections (66.7% preoperatively; 54.5% postoperatively). A trend showing a more rapid pre- to postoperative decrease in local efficiency was found in class I CHD neonates compared to controls. In CHD neonates, larger WMI volume was associated with lower strength (p=0.0026) and global efficiency (p=0.0097). The maturation of the structural connectome is delayed in neonates with CHD, with a pattern of lower structural integration and higher segregation compared to healthy controls. Trend-level evidence indicated that normalized postoperative cardiac physiology in class I CHD neonates might improve structural network topology. In contrast, the degree of WMI burden negatively impacts network strength and integration. Further research is needed to elucidate how aberrant structural network development in CHD represents neural correlates of later neurodevelopmental impairments.

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Section: Reduced Integration and Higher Segregation Of Global And Nodcontrasting

confidence: 76%

Delayed maturation of the structural brain connectome in neonates with congenital heart disease

Feldmann

Guo

Miller

et al. 2020

Preprint

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“…alterations in neural networks are present in neonates with CHD prior to surgery 39 , these data suggest that changes in neural connectivity could be secondary to mutations in the genome rather than solely due to hemodynamic factors, and recent genomic studies have identified candidate genes common to children with CHD and those with NDD, suggesting a genetic basis for CHD-associated NDD 23,24,40,41 . In these subjects, genetic substitutions affect genes involved in chromatin modification, morphogenesis and transcriptional regulation of neuronal tissues as well as in the heart.…”

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confidence: 90%

De novo damaging variants associated with congenital heart diseases contribute to the connectome

Ji¹,

Ferdman²,

Copel³

et al. 2020

Sci Rep

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congenital heart disease (cHD) survivors are at risk for neurodevelopmental disability (nDD), and recent studies identify genes associated with both disorders, suggesting that nDD in cHD survivors may be of genetic origin. Genes contributing to neurogenesis, dendritic development and synaptogenesis organize neural elements into networks known as the connectome. We hypothesized that nDD in cHD may be attributable to genes altering both neural connectivity and cardiac patterning. to assess the contribution of de novo variants (DNVs) in connectome genes, we annotated 229 published NDD genes for connectome status and analyzed data from 3,684 CHD subjects and 1,789 controls for connectome gene mutations. cHD cases had more protein truncating and deleterious missense DnVs among connectome genes compared to controls (oR = 5.08, 95%CI:2.81-9.20, Fisher's exact test P = 6.30E-11). When removing three known syndromic CHD genes, the findings remained significant (OR = 3.69, 95%CI:2.02-6.73, Fisher's exact test P = 1.06E-06). In CHD subjects, the top 12 NDD genes with damaging DNVs that met statistical significance after Bonferroni correction (PTPN11,

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“…Non-Central Nervous System (CNS) diseases could also alter brain FC in the newborns. A neonatal congenital heart disease study found that hub or rich-club nodes had reduced FC in full-term newborns with neonatal congenital heart disease when compared to the healthy term controls (De Asis-Cruz et al, 2018). It also indicates that such a pathological attack only targets local hub regions in the subcortical regions and brain stem, as well as the thalamocortical connections.…”

Section: Neurodevelopmental Disorders and Other Diseases Or Hazardousmentioning

confidence: 99%

Resting-state functional MRI studies on infant brains: A decade of gap-filling efforts

2019

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Resting-state functional MRI (rs-fMRI) is one of the most prevalent brain functional imaging modalities. Previous rs-fMRI studies have mainly focused on adults and elderly subjects. Recently, infant rs-fMRI studies have become an area of active research. After a decade of gap filling studies, many facets of the brain functional development from early infancy to toddler has been uncovered. However, infant rs-fMRI is still in its infancy. The image analysis tools for neonates and young infants can be quite different from those for adults. From data analysis to result interpretation, more questions and issues have been raised, and new hypotheses have been formed. With the anticipated availability of unprecedented high-resolution rs-fMRI and dedicated analysis pipelines from the Baby Connectome Project (BCP), it is important now to revisit previous findings and hypotheses, discuss and comment existing issues and problems, and make a "to-do-list" for the future studies. This review article aims to comprehensively review a decade of the findings, unveiling hidden jewels of the fields of developmental neuroscience and neuroimage computing. Emphases will be given to early infancy, particularly the first few years of life. In this review, an end-to-end summary, from infant rs-fMRI experimental design to data processing, and from the development of individual functional systems to large-scale brain functional networks, is provided. A comprehensive summary of the rs-fMRI findings in developmental patterns is highlighted. Furthermore, an extensive summary of the neurodevelopmental disorders and the effects of other hazardous factors is provided. Finally, future research trends focusing on emerging dynamic functional connectivity and state-of-the-art functional connectome analysis are summarized. In next decade, early infant rs-fMRI and developmental connectome study could be one of the shining research topics.

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Aberrant brain functional connectivity in newborns with congenital heart disease before cardiac surgery

Cited by 53 publications

References 58 publications

Delayed maturation of the structural brain connectome in neonates with congenital heart disease

Delayed maturation of the structural brain connectome in neonates with congenital heart disease

De novo damaging variants associated with congenital heart diseases contribute to the connectome

Resting-state functional MRI studies on infant brains: A decade of gap-filling efforts

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