Altered brain metabolism contributes to executive function deficits in school-aged children born very preterm

Abstract

Background Executive function deficits in children born very preterm (VPT) have been linked to anatomical abnormalities in white matter and subcortical brain structures. This study aimed to investigate how altered brain metabolism contributes to these deficits in VPT children at school-age. Methods Fifty-four VPT participants aged 8–13 years and 62 term-born peers were assessed with an executive function test battery. Brain metabolites were obtained in the frontal white matter and the basal ganglia/thalami, using proton magnetic resonance spectroscopy (MRS). N-acetylaspartate (NAA)/creatine (Cr), choline (Cho)/Cr, glutamate + glutamine (Glx)/Cr, and myo-Inositol (mI)/Cr were compared between groups and associations with executive functions were explored using linear regression. Results In the frontal white matter, VPT showed lower Glx/Cr (mean difference: −5.91%, 95% CI [−10.50, −1.32]), higher Cho/Cr (7.39%, 95%-CI [2.68, 12.10]), and higher mI/Cr (5.41%, 95%-CI [0.18, 10.64]) while there were no differences in the basal ganglia/thalami. Lower executive functions were associated with lower frontal Glx/Cr ratios in both groups (β = 0.16, p = 0.05) and higher mI/Cr ratios in the VPT group only (interaction: β = −0.17, p = 0.02). Conclusion Long-term brain metabolite alterations in the frontal white matter may be related to executive function deficits in VPT children at school-age. Impact Very preterm birth is associated with long-term brain metabolite alterations in the frontal white matter. Such alterations may contribute to deficits in executive function abilities. Injury processes in the brain can persist for years after the initial insult. Our findings provide new insights beyond structural and functional imaging, which help to elucidate the processes involved in abnormal brain development following preterm birth. Ultimately, this may lead to earlier identification of children at risk for developing deficits and more effective interventions.

Disrupted metabolic and spontaneous neuronal activity of hippocampus in sepsis associated encephalopathy rats: A study combining magnetic resonance spectroscopy and resting-state functional magnetic resonance imaging

“…Recent research demonstrated that mI can cause glial cells differentiation, and that the elevation of the mI/Cr ratio is often interpreted to reflect glial cell activation (Schnider et al, 2020). With a focus on changes in immunofluorescence staining results after CLP surgery, we observed that microglial cells activated in the hippocamp of SAE rats, which supported the hypothesis The ALFF values and metabolites in the hippocampus were negatively correlated with duration in the target quadrant.…”

Altered white matter microstructure is related to cognition in adults with congenital heart disease

“…inhibition, cognitive flexibility, working memory, verbal and nonverbal fluency and problem solving) and associated sub-tests. However, mean executive function composite scores have been used previously to demonstrate associations between neurological correlates and executive function ( Nosarti et al , 2008 ; Wehrle et al , 2017 ; Schnider et al , 2020 ).…”

“…A global score derived from an extensive test battery was used under the assumption that executive function is a multi-dimensional construct including different cognitive processes that can be distinguished but which are correlated [see systematic review by ( Baggetta and Alexander, 2016 )]. Using a mean composite score further decreases multiple testing and associated Type 1 errors and has been successfully applied in other neuroimaging studies in at risk populations ( Nosarti et al , 2008 ; Wehrle et al , 2017 ; Schnider et al , 2020 ).…”

Effects of Correcting for Prematurity on Executive Function Scores of Children Born Very Preterm at School Age

“…The EpoKids study is an ongoing follow-up study investigating the long-term effect of early erythropoietin administration on executive functions in children born between 26 and 32 weeks of gestational age 17 . The current analysis uses data on the subgroup of children who were assessed between 2017 and 2019 (for details, see 18 ). The Neuropsychology and Memory (NEMO) research programme was run between 2011 and 2015 and assessed cognitive development and training-induced improvements of cognitive abilities in school-aged children born before 32 weeks of gestational age or with a birth weight below 1500 grams 19 .…”