Structural network topology correlates of microstructural brain dysmaturation in term infants with congenital heart disease

Abstract

Neonates with complex congenital heart disease (CHD) demonstrate microstructural brain dysmaturation, but the relationship with structural network topology is unknown. We performed diffusion tensor imaging (DTI) in term neonates with CHD preoperatively (N = 61) and postoperatively (N = 50) compared with healthy term controls (N = 91). We used network topology (graph) analyses incorporating different weighted and unweighted approaches and subject-specific white matter segmentation to investigate structural topology differences, as well as a voxel-based analysis (VBA) to confirm the presence of microstructural dysmaturation. We demonstrate cost-dependent network inefficiencies in neonatal CHD in the pre- and postoperative period compared with controls, related to microstructural differences. Controlling for cost, we show the presence of increased small-worldness (hierarchical fiber organization) in CHD infants preoperatively, that persists in the postoperative period compared with controls, suggesting the early presence of brain reorganization. Taken together, topological microstructural dysmaturation in CHD infants is accompanied by hierarchical fiber organization during a protracted critical period of early brain development. Our methodology also provides a pipeline for quantitation of network topology changes in neonates and infants with microstructural brain dysmaturation at risk for perinatal brain injury.

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

“…They can be summarized as a pattern of reduced integration and increased segregation. Similar findings of a perturbated network architecture in CHD neonates compared to controls were reported by Schmithorst et al (Schmithorst et al 2018). In their study CHD neonates underwent either pre-or postoperative MRI.…”

“…Furthermore, we were able to reveal perturbations in network segregation. In contrast to our analysis, CHD neonates with any type of brain injury were excluded in Schmithorst et al (Schmithorst et al 2018). We assume that our results are more representative of network disturbances found in CHD neonates as perioperative brain injury, such as punctate WMI and focal stroke, are common in CHD (Peyvandi et al 2019).…”

“…Weighted, undirected connectivity networks were formed. The connectivity or edge weight was defined as the mean fractional anisotropy (FAmean) value of all tractography streamlines connecting the regions at the two endpoints, as these networks have been shown to be most sensitive to microstructural dysmaturation of the white matter in neonates with CHD (Schmithorst et al 2018). Nodes corresponded to the AAL ROIs in subject space.…”

Reduced structural connectivity in cortico-striatal-thalamic network in neonates with congenital heart disease

“…local) connectivity is disrupted ( Fischi-Gomez et al, 2016 , Karolis et al, 2016 , Batalle et al, 2017 , Ball et al, 2014 ). In neonates with CHD, recent studies have demonstrated reduced functional connectivity ( De Asis-Cruz et al, 2018 ) and alterations in structural network topology pre-operatively ( Schmithorst et al, 2018 ). However, it is not clear whether altered structural network topology in infants with CHD prior to surgery can be explained by disruptions to core-peripheral connections.…”

Cognitive flexibility in critical CHD: a target for intervention

“…3 Indeed, it is now understood that brain development within the context of critical CHD (i.e., CHDs requiring intensive surgical intervention(s) to sustain life) is often atypical, with signs of deviation from expected neuronal maturation and volumetric trajectories recognisable as early as the late-second/early-third prenatal trimester [4][5][6][7][8] and evidence of structural, functional, and network topological brain abnormalities documented throughout adolescence and young adulthood. [9][10][11][12][13][14][15][16][17][18][19][20] Children and adolescents with critical CHD are also at heightened risk for a range of neurobehavioural and psychosocial challenges, 21 most notably in executive function. [22][23][24][25] Executive function is an umbrella term, encompassing three core components: inhibitory control, working memory, and cognitive flexibility.…”