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Rewiring the extremely preterm brain: Altered structural connectivity relates to language function
Maria E Barnes-Davis1, Brady J Williamson2, Stephanie L Merhar1
1Perinatal Institute, Cincinnati Children's Hospital Medical Center, United States; Department of Pediatrics, University of Cincinnati College of Medicine, United States.
Insights
Children born extremely preterm show altered brain wiring, with increased connections outside the corpus callosum supporting language skills. This may indicate a pathway for brain resilience after preterm birth.
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Pediatric Neurology
Background:
- Children born extremely preterm (<28 weeks) face higher risks of cognitive and language impairments.
- Previous studies show conflicting findings of increased functional connectivity but decreased corpus callosum integrity in preterm children.
- The anatomical basis for observed functional hyperconnectivity in preterm infants remains unclear.
Purpose of the Study:
- To investigate structural connectivity differences in school-aged children born extremely preterm compared to term-born controls.
- To explore the relationship between structural connectivity, particularly extracallosal pathways, and language function in preterm children.
- To identify potential anatomical substrates underlying functional hyperconnectivity and brain resiliency in extremely preterm infants.
Main Methods:
- Employed advanced connectometry analyses (whole-brain and functionally-constrained) on neuroimaging data from 12 extremely preterm and 10 term-born children (aged 4-6 years).
- Assessed structural connectivity, focusing on the corpus callosum and extracallosal pathways, particularly between bilateral temporal regions.
- Correlated structural connectivity measures with performance on standardized language assessments.
Main Results:
- Extremely preterm children exhibited decreased connectivity within the corpus callosum and increased connectivity in the cerebellum compared to controls.
- Significantly increased extracallosal structural connectivity between bilateral temporal regions was observed in preterm children.
- Connectivity within these extracallosal pathways positively correlated with language performance in preterm children but not in controls.
Conclusions:
- This study identifies anatomical substrates for increased interhemispheric functional connectivity in extremely preterm children.
- Increased reliance on extracallosal pathways may represent a compensatory mechanism or biomarker for resiliency following extremely preterm birth.
- Findings highlight the importance of exploring atypical brain wiring for understanding neurodevelopmental outcomes in preterm populations.
Abstract:
Children born preterm are at increased risk for cognitive impairment, with higher-order functions such as language being especially vulnerable. Previously, we and others have reported increased interhemispheric functional connectivity in children born extremely preterm; the finding appears at odds with literature showing decreased integrity of the corpus callosum, the primary commissural bundle, in preterm children. We address the apparent discrepancy by obtaining advanced measures of structural connectivity in twelve school-aged children born extremely preterm (<28 weeks) and ten term controls. We hypothesize increased extracallosal structural connectivity might support the functional hyperconnectivity we had previously observed. Participants were aged four to six years at time of study and groups did not differ in age, sex, race, ethnicity, or socioeconomic status. Whole-brain and language-network-specific (functionally-constrained) connectometry analyses were performed. At the whole-brain level, preterm children had decreased connectivity in the corpus callosum and increased connectivity in the cerebellum versus controls. Functionally-constrained analyses revealed significantly increased extracallosal connectivity between bilateral temporal regions in preterm children (FDRq <0.05). Connectivity within these extracallosal pathways was positively correlated with performance on standardized language assessments in children born preterm (FDRq <0.001), but unrelated to performance in controls. This is the first study to identify anatomical substrates for increased interhemispheric functional connectivity in children born preterm; increased reliance on an extracallosal pathway may represent a biomarker for resiliency following extremely preterm birth.
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