Increased Cerebello-Prefrontal Connectivity Predicts Poor Executive Function in Congenital Heart Disease
Aurelia Sahel1,2, Rafael Ceschin1,2, Daryaneh Badaly3
1Department of Radiology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Insights
Congenital heart disease (CHD) in youth is linked to altered brain connectivity, particularly in cognitive pathways. This study shows specific connectivity changes predict cognitive and motor deficits in children with CHD.
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Pediatric Cardiology
Background:
- Children and adolescents with congenital heart disease (CHD) face risks of cognitive impairments, including executive function deficits and motor delays.
- These deficits can negatively impact academic performance, adaptive functioning, and overall quality of life.
Purpose of the Study:
- To investigate differences in prefrontal-cerebellar brain connectivity between individuals with CHD and healthy controls.
- To determine if these connectivity alterations can predict cognitive or motor impairments in youth with CHD.
Main Methods:
- Utilized multi-modal magnetic resonance imaging (MRI), including diffusion tensor imaging, on 53 participants with CHD and 73 healthy controls.
- Measured cerebellum-to-frontal cortex connectivity using probabilistic tractography.
- Assessed cognitive and motor skills via NIH Toolbox neuropsychological tests.
Main Results:
- Individuals with CHD showed increased fractional anisotropy (FA) in cognitive loop connectivity pathways compared to controls.
- No significant differences in motor loop connectivity were found between groups.
- Increased FA in a specific cognitive loop tract predicted lower executive functioning scores in CHD participants.
- Adolescents with CHD exhibited a transient increase in cognitive loop connectivity compared to younger or older individuals.
Conclusions:
- Altered cerebellum-cerebral connectivity within cognitive loops is associated with cognitive dysfunction in youth with CHD.
- The adolescent period appears critical for cerebellar circuitry plasticity influencing neurocognitive function in CHD.
- Further validation in diverse pediatric CHD cohorts is recommended.
Background:
Children and adolescents with congenital heart disease (CHD) are at risk for cognitive impairments, such as executive function deficits and motor delays, which can impact their academic and adaptive functioning as well as their quality of life. We investigated whether alterations in connectivity between the prefrontal and cerebellar brain structures exist between CHD and control cohorts and if these alterations could predict cognitive or motor impairment among youths with CHD.
Methods:
53 participants with CHD and 73 healthy control participants completed multi-modal magnetic resonance imaging (MRI) of the brain, including high-resolution diffusion tensor imaging at 3T. We measured connectivity from masked regions of interest in the cerebellum to the frontal cortex using a probabilistic tractography method. Participants also completed neuropsychological tests of cognitive and motor skills using the NIH Toolbox.
Results:
In the CHD group, fractional anisotropy (FA) was increased in the cognitive loop connectivity pathways, including from the right cerebellum to the left thalamus (p = 0.0002) and from the left thalamus to the left medial frontal gyrus (MFG) (p = 0.0048) compared with the healthy control group. In contrast, there were no differences between CHD and controls in motor loop connectivity pathways. An increase in FA from the right thalamus to the MFG tract in the cognitive loop (posterior subdivision) predicted (p = 0.03) lower scores on the NIHTB tests, including those of executive functioning. A transient increase in connectivity of the cognitive loop in the adolescent group was observed relative to the child and adult groups.
Conclusions:
Our results suggest that selective alteration of cerebellum-cerebral connectivity circuitry within the cognitive loops predicts cognitive dysfunction in CHD youth. Our study suggests a critical period of cerebellar circuitry plasticity in the adolescent period in CHD subjects that drives neurocognitive function. Further replication and validation in other pediatric CHD cohorts is warranted for future work.
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