Hippocampal alterations and functional correlates in adolescents and young adults with congenital heart disease

Abstract

There is a high prevalence of neurodevelopmental impairments in individuals living with congenital heart disease (CHD) and the neural correlates of these impairments are not yet fully understood. Recent studies have shown that hippocampal volume and shape differences may provide unique biomarkers for neurodevelopmental disorders. The hippocampus is vulnerable to early life injury, especially in populations at risk for hypoxemia or hemodynamic instability such as in neonates with CHD. We compared hippocampal gray and white matter volume and morphometry between youth born with CHD (n = 50) aged 16–24 years and healthy peers (n = 48). We also explored whether hippocampal gray and white matter volume and morphometry are associated with executive function and self‐regulation deficits. To do so, participants underwent 3T brain magnetic resonance imaging and completed the self‐reported Behavior Rating Inventory of Executive Function—Adult version. We found that youth with CHD had smaller hippocampal volumes (all statistics corrected for false discovery rate; q < 0.05) as compared to controls. We also observed significant smaller surface area bilaterally and inward displacement on the left hippocampus predominantly on the ventral side (q < 0.10) in the CHD group that were not present in the controls. Left CA1 and CA2/3 were negatively associated with working memory (p < .05). Here, we report, for the first‐time, hippocampal morphometric alterations in youth born with CHD when compared to healthy peers, as well as, structure–function relationships between hippocampal volumes and executive function. These differences may reflect long lasting alterations in brain development specific to individual with CHD.

Reduced hippocampal volumes and memory deficits in adolescents with single ventricle heart disease

“…Both left and right hippocampal volumes showed significant associations with worse cognitive scores, including memory, but not with anxiety and depression. Other studies that examined hippocampal volumes showed significant bilateral differences between school‐age children with CHD and controls (Fontes et al., 2019; Latal et al., 2016; Munoz‐Lopez et al., 2017). However, our findings could reflect the evaluation of only the SVHD subgroup compared to studies with mixed types of CHD (Fontes et al., 2019; Latal et al., 2016).…”

“…Other studies that examined hippocampal volumes showed significant bilateral differences between school‐age children with CHD and controls (Fontes et al., 2019; Latal et al., 2016; Munoz‐Lopez et al., 2017). However, our findings could reflect the evaluation of only the SVHD subgroup compared to studies with mixed types of CHD (Fontes et al., 2019; Latal et al., 2016). By focusing on this subset with cyanotic CHD and excluding other risk factors, such as premature birth (<37 weeks gestation), previous stroke, cardiac arrest, or the use of ECMO, the present study was able to control for additional factors that may have influenced hippocampal volume (age and TBV).…”

“…Recent studies showed hippocampal volume correlations with memory impairments (i.e., working memory, episodic memory, and verbal comprehension) in a group of patients with transposition of the great arteries who underwent the arterial switch operation (Munoz‐Lopez et al., 2017) and subjects with multiple types of CHD after surgical intervention (Fontes et al., 2019; Latal et al., 2016). However, these studies utilized different CHD populations, included subjects with other potential risk factors for hippocampal volume loss (i.e., prematurity, previous extracorporeal membrane oxygenation (ECMO) use, and stroke), different cognitive measures, and methods to assess hippocampal volumes (i.e., gold standard manual tracings vs. automated processes) (Fontes et al., 2019; Latal et al., 2016; Munoz‐Lopez et al., 2017). Furthermore, there are no published studies that have examined the correlations between memory, anxiety, and mood scores to hippocampal volumes in the SVHD population using objective measures (i.e., manual tracing of structures).…”

Multi-Slice Radiomic Analysis of Apparent Diffusion Coefficient Metrics Improves Evaluation of Brain Alterations in Neonates With Congenital Heart Diseases

“…Functional imaging was used to study brain maturity and injury in neonates with CHD (8,9). For example, magnetic resonance spectroscopy studies showed that neonates with cyanotic CHD exhibit characteristic decreased ratio of Nacteyl-aspartate to choline in the thalamus, basal ganglia, and corticospinal tracts (1).…”

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.…”