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Fiber-Specific Measures of White Matter Microstructure and Macrostructure Are Associated With Internalizing and
Courtney P Gilchrist1, Claire E Kelly2, Angela Cumberland3
1School of Health and Biomedical Sciences, RMIT University, Melbourne, Victoria, Australia; Victorian Infant Brain Studies, Murdoch Children's Research Institute, Melbourne, Victoria, Australia; Developmental Imaging, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
Insights
White matter development in very preterm (VP) children is linked to behavior. Fixel-based analysis revealed specific white matter changes correlating with internalizing and externalizing problems at age 7, with some associations persisting at age 13.
Area of Science:
- Neuroimaging
- Developmental Neuroscience
- Behavioral Science
Background:
- Delayed white matter development in very preterm (VP) individuals is associated with adverse behavioral outcomes.
- Previous tensor-based models lack specificity in identifying these associations.
- Fixel-based analysis offers a more refined approach to examine white matter correlates of behavior.
Purpose of the Study:
- To investigate white matter microstructural and macrostructural correlates of internalizing and externalizing problems in very preterm (VP) and full-term (FT) children.
- To compare these associations at ages 7 and 13 years using a fixel-based analysis framework.
- To identify age-specific neurobiological markers for behavioral problems in high-risk populations.
Main Methods:
- Longitudinal diffusion imaging data from 130 VP and 29 FT children at 7 years, and 125 VP and 44 FT children at 13 years.
- Fixel-based measures (fiber density, cross-section, and combined) extracted from 21 white matter tracts.
- Internalizing and externalizing symptoms assessed via parent-reported Strengths and Difficulties Questionnaire.
Main Results:
- At age 7, reduced fiber density and cross-section were linked to increased internalizing and externalizing symptoms in both VP and FT groups.
- At age 13, fixel-based measures did not correlate with internalizing symptoms.
- At age 13, reduced white matter integrity measures were associated with externalizing symptoms, but only in the full-term (FT) group.
Conclusions:
- Age-specific neurobiological markers for internalizing and externalizing problems were identified.
- Findings extend previous tensor-based research and inform pathophysiological models of behavior problems.
- Results provide a foundation for developing interventions to mitigate behavioral risks in VP and other high-risk populations.
Background:
Tensor-based investigations suggest that delayed or disrupted white matter development may relate to adverse behavioral outcomes in individuals born very preterm (VP); however, metrics derived from such models lack specificity. Here, we applied a fixel-based analysis framework to examine white matter microstructural and macrostructural correlates of concurrent internalizing and externalizing problems in VP and full-term (FT) children at 7 and 13 years.
Methods:
Diffusion imaging data were collected in a longitudinal cohort of VP and FT individuals (130 VP and 29 FT at 7 years, 125 VP and 44 FT at 13 years). Fixel-based measures of fiber density, fiber-bundle cross-section, and fiber density and cross-section were extracted from 21 white matter tracts previously implicated in psychopathology. Internalizing and externalizing symptoms were assessed using the Strengths and Difficulties Questionnaire parent report at 7 and 13 years.
Results:
At age 7 years, widespread reductions in fiber-bundle cross-section and fiber density and cross-section and tract-specific reductions in fiber density were related to more internalizing and externalizing symptoms irrespective of birth group. At age 13 years, fixel-based measures were not related to internalizing symptoms, while tract-specific reductions in fiber density, fiber-bundle cross-section, and fiber density and cross-section measures were related to more externalizing symptoms in the FT group only.
Conclusions:
Age-specific neurobiological markers of internalizing and externalizing problems identified in this study extend previous tensor-based findings to inform pathophysiological models of behavior problems and provide the foundation for investigations into novel preventative and therapeutic interventions to mitigate risk in VP and other high-risk infant populations.
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