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.

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Executive function deficits mediate the association between very preterm birth and behavioral problems at school-age

Early Human Development ◽

10.1016/j.earlhumdev.2020.105076 ◽

2020 ◽

Vol 146 ◽

pp. 105076

Author(s):

Barbara Schnider ◽

Vera Disselhoff ◽

Ulrike Held ◽

Beatrice Latal ◽

Cornelia F. Hagmann ◽

...

Keyword(s):

Executive Function ◽

Preterm Birth ◽

Behavioral Problems ◽

School Age ◽

Very Preterm ◽

Very Preterm Birth ◽

Executive Function Deficits

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1266 Intrauterine Growth Restriction and Very Preterm Birth are Associated with Motor Dysfunction and White Matter Pathology at School Age

Archives of Disease in Childhood ◽

10.1136/archdischild-2012-302724.1266 ◽

2012 ◽

Vol 97 (Suppl 2) ◽

pp. A362-A362

Author(s):

E. Morsing ◽

A. Kahn ◽

D. Ley ◽

I. Bjorkman-Burtscher ◽

K. Marsal

Keyword(s):

Preterm Birth ◽

White Matter ◽

Intrauterine Growth Restriction ◽

Growth Restriction ◽

Motor Dysfunction ◽

School Age ◽

Intrauterine Growth ◽

Very Preterm ◽

Very Preterm Birth ◽

White Matter Pathology

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Faculty Opinions recommendation of Altered brain metabolism contributes to executive function deficits in school-aged children born very preterm.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.738214770.793578674 ◽

2020 ◽

Author(s):

Chiara Nosarti

Keyword(s):

Executive Function ◽

Brain Metabolism ◽

School Aged Children ◽

Very Preterm ◽

Executive Function Deficits

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Long-term outcomes of very preterm birth: ‘white matter’ matters

Developmental Medicine & Child Neurology ◽

10.1111/dmcn.12239 ◽

2013 ◽

Vol 55 (10) ◽

pp. 883-884 ◽

Cited By ~ 2

Author(s):

Jorrit F de Kieviet

Keyword(s):

Preterm Birth ◽

White Matter ◽

Long Term Outcomes ◽

Very Preterm ◽

Very Preterm Birth

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Mapping of long-term cognitive and motor deficits in pediatric cerebellar brain tumor survivors into a cerebellar white matter atlas

Child s Nervous System ◽

10.1007/s00381-021-05244-2 ◽

2021 ◽

Author(s):

Frederik Grosse ◽

Stefan Mark Rueckriegel ◽

Ulrich-Wilhelm Thomale ◽

Pablo Hernáiz Driever

Keyword(s):

Brain Tumor ◽

Executive Function ◽

Cognitive Function ◽

White Matter ◽

Cerebellar Nuclei ◽

Motor Deficits ◽

Deep Cerebellar Nuclei ◽

Cerebellar White Matter ◽

Lesion Symptom Mapping

Abstract Purpose Diaschisis of cerebrocerebellar loops contributes to cognitive and motor deficits in pediatric cerebellar brain tumor survivors. We used a cerebellar white matter atlas and hypothesized that lesion symptom mapping may reveal the critical lesions of cerebellar tracts. Methods We examined 31 long-term survivors of pediatric posterior fossa tumors (13 pilocytic astrocytoma, 18 medulloblastoma). Patients underwent neuronal imaging, examination for ataxia, fine motor and cognitive function, planning abilities, and executive function. Individual consolidated cerebellar lesions were drawn manually onto patients’ individual MRI and normalized into Montreal Neurologic Institute (MNI) space for further analysis with voxel-based lesion symptom mapping. Results Lesion symptom mapping linked deficits of motor function to the superior cerebellar peduncle (SCP), deep cerebellar nuclei (interposed nucleus (IN), fastigial nucleus (FN), ventromedial dentate nucleus (DN)), and inferior vermis (VIIIa, VIIIb, IX, X). Statistical maps of deficits of intelligence and executive function mapped with minor variations to the same cerebellar structures. Conclusion We identified lesions to the SCP next to deep cerebellar nuclei as critical for limiting both motor and cognitive function in pediatric cerebellar tumor survivors. Future strategies safeguarding motor and cognitive function will have to identify patients preoperatively at risk for damage to these critical structures and adapt multimodal therapeutic options accordingly.

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Listening to Mom in the NICU: effects of increased maternal speech exposure on language outcomes and white matter development in infants born very preterm

Trials ◽

10.1186/s13063-021-05385-4 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Edith Brignoni-Pérez ◽

Maya Chan Morales ◽

Virginia A. Marchman ◽

Melissa Scala ◽

Heidi M. Feldman ◽

...

Keyword(s):

White Matter ◽

Structural Connectivity ◽

Receptive Language ◽

Secondary Outcome ◽

Language Outcomes ◽

Theoretical Understanding ◽

Very Preterm ◽

White Matter Development ◽

Maternal Speech

Abstract Background Infants born very preterm (< 32 weeks gestational age (GA)) are at risk for developmental language delays. Poor language outcomes in children born preterm have been linked to neurobiological factors, including impaired development of the brain’s structural connectivity (white matter), and environmental factors, including decreased exposure to maternal speech in the neonatal intensive care unit (NICU). Interventions that enhance preterm infants’ exposure to maternal speech show promise as potential strategies for improving short-term health outcomes. Intervention studies have yet to establish whether increased exposure to maternal speech in the NICU offers benefits beyond the newborn period for brain and language outcomes. Methods This randomized controlled trial assesses the long-term effects of increased maternal speech exposure on structural connectivity at 12 months of age (age adjusted for prematurity (AA)) and language outcomes between 12 and 18 months of age AA. Study participants (N = 42) will include infants born very preterm (24–31 weeks 6/7 days GA). Newborns are randomly assigned to the treatment (n = 21) or standard medical care (n = 21) group. Treatment consists of increased maternal speech exposure, accomplished by playing audio recordings of each baby’s own mother reading a children’s book via an iPod placed in their crib/incubator. Infants in the control group have the identical iPod setup but are not played recordings. The primary outcome will be measures of expressive and receptive language skills, obtained from a parent questionnaire collected at 12–18 months AA. The secondary outcome will be measures of white matter development, including the mean diffusivity and fractional anisotropy derived from diffusion magnetic resonance imaging scans performed at around 36 weeks postmenstrual age during the infants’ routine brain imaging session before hospital discharge and 12 months AA. Discussion The proposed study is expected to establish the potential impact of increased maternal speech exposure on long-term language outcomes and white matter development in infants born very preterm. If successful, the findings of this study may help to guide NICU clinical practice for promoting language and brain development. This clinical trial has the potential to advance theoretical understanding of how early language exposure directly changes brain structure for later language learning. Trial registration NIH Clinical Trials (ClinicalTrials.gov) NCT04193579. Retrospectively registered on 10 December 2019.

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