Cerebellar and Prefrontal Structures Associated With Executive Functioning in Pediatric Patients With Congenital Heart Defects

Abstract

ObjectiveChildren, adolescents, and young adults with congenital heart defects (CHD) often display executive dysfunction. We consider the prefrontal and cerebellar brain structures as mechanisms for executive dysfunction among those with CHD.Methods55 participants with CHD (M age = 13.93) and 95 healthy controls (M age = 13.13) completed magnetic resonance imaging (MRI) of the brain, from which we extracted volumetric data on prefrontal and cerebellar regions. Participants also completed neuropsychological tests of executive functioning; their parents completed ratings of their executive functions.ResultsCompared to healthy controls, those with CHD had smaller cerebellums and lateral, medial, and orbital prefrontal regions, they performed more poorly on tests of working memory, inhibitory control, and mental flexibility, and their parents rated them as having poorer executive functions across several indices. Across both groups, there were significant correlations for cerebellar and/or prefrontal volumes with cognitive assessments of working memory, mental flexibility, and inhibitory control and with parent-completed ratings of task initiation, working memory, and planning/organization. Greater prefrontal volumes were associated with better working memory, among those with larger cerebellums (with group differences based on the measure and the prefrontal region). Greater prefrontal volumes were related to better emotional regulation only among participants with CHD with smaller cerebellar volumes, and with poorer inhibition and emotional regulation only among healthy controls with larger cerebellar volumes.ConclusionThe cerebellum not only contributes to executive functioning among young individuals with CHD but may also modulate the relationships between prefrontal regions and executive functioning differently for pediatric patients with CHD vs. health controls.

The cerebellum and cognitive function: anatomical evidence from a transdiagnostic sample

“…Animal research evidence indicated that hemi-cerebellectomized animals are unable to flexibly switch to a new set of rules, despite having intact motor responses (De Bartolo et al 2009; Dickson et al 2017). A few small-sample human studies (Ben-Soussan et al 2015; Kansal et al 2017; Badaly et al 2022; Kühn et al 2012; Paradiso et al 1997; Parker et al 2008; Koppelmans et al 2017; Bauer et al 2009; Bernard and Seidler 2013) have underlined a cerebellar role in mediating cognitive flexibility. The cerebellar correspondence of cognitive flexibility fits well with evidence from cerebellar lesions (Stoodley and Schmahmann 2010; Argyropoulos et al 2020; Stoodley et al 2016) and theoretical accounts of cognitive dysmetria theory (Andreasen, Paradiso, and O’Leary 1998).…”

Functional network organization is locally atypical in children and adolescents with congenital heart disease

“…While prior studies indicate structural brain network reorganization, our findings suggest that the global functional network remains largely undifferentiated, with predominantly regional differences. Regional, rather than global differences, may explain higher variance observed in CHD patient scores, but still within normal limits on tests of intelligence (Badaly et al, 2022; Wallace et al, 2023)…”

Development and Validation of a Paralimbic Related Subcortical Brain Dysmaturation MRI Score in Infants with Congenital Heart Disease

“…al found that preterm infants with exposure to morphine in the neonatal period had decreased cerebellar volumes and worse neurodevelopmental outcomes. 79 Additionally, our group has previously shown that CHD children with reduced cerebellar volumes scored worse in tests for working memory, inhibitory control, and mental flexibility 80 . We also demonstrated that the superior surface of the cerebellum, primarily composed of the posterior lobe and the midline vermis, is an area particularly susceptible to alterations in morphology, indicating possible regions specifically affected by dysmaturation in CHD.…”