Abstract
Background
Very preterm (VP) children are at risk of memory and emotional impairments; however, the neural correlates remain incompletely defined. This study investigated the effect of VP birth on white matter tracts traditionally related to episodic memory and emotion.
Methods
The cingulum, fornix, uncinate fasciculus, medial forebrain bundle and anterior thalamic radiation were reconstructed using tractography in 144 VP children and 33 full-term controls at age 7 years.
Results
Compared with controls, VP children had higher axial, radial, and mean diffusivities and neurite orientation dispersion, and lower volume and neurite density in the fornix, along with higher neurite orientation dispersion in the medial forebrain bundle. Support vector classification models based on tract measures significantly classified VP children and controls. Higher fractional anisotropy and lower diffusivities in the cingulum, uncinate fasciculus, medial forebrain bundle and anterior thalamic radiation were associated with better episodic memory, independent of key perinatal risk factors. Support vector regression models using tract measures did not predict episodic memory and emotional outcomes.
Conclusions
Altered tract structure is related to adverse episodic memory outcomes in VP children, but further research is required to determine the ability of tract structure to predict outcomes of individual children.
Impact
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We studied white matter fibre tracts thought to be involved in episodic memory and emotion in VP and full-term children using diffusion magnetic resonance imaging and machine learning.
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VP children have altered fornix and medial forebrain bundle structure compared with full-term children.
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Altered tract structure can be detected using machine learning, which accurately classified VP and full-term children using tract data.
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Altered cingulum, uncinate fasciculus, medial forebrain bundle and anterior thalamic radiation structure was associated with poorer episodic memory skills using linear regression.
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The ability of tract structure to predict episodic memory and emotional outcomes of individual children based on support vector regression was limited.
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Acknowledgements
This research was conducted within the VIBeS and Developmental Imaging research groups, located at the Murdoch Children’s Research Institute, as well as the Children’s MRI Centre, located at the Royal Children’s Hospital, Melbourne, Victoria, Australia. We thank members of the VIBeS and Developmental Imaging teams, including Merilyn Bear for recruitment of the children in this study, the Royal Children’s Hospital Medical Imaging staff for their assistance and expertise in the collection of the MRI data included in this study, Wai Yen Loh for development of a pipeline to segment the subcortical brain regions that were used in this study and the families and children for participating in this study. This study was supported by the National Health and Medical Research Council of Australia (Project Grant No. 237117 to T.E.I. and L.W.D.; Project Grant No. 491209 to P.J.A., T.E.I., L.W.D.; Centre of Research Excellence No. 1060733 to L.W.D., P.J.A., J.L.Y.C. and D.K.T.; Early Career Fellowship No. 1012236 to D.K.T. and 1053787 to J.L.Y.C.; Career Development Fellowship No. 1085754 to D.K.T. and No. 1141354 to J.L.Y.C.; Senior Research Fellowship No. 1081288 to P.J.A.). This study was also supported by the National Institutes of Health (NIH; Grant No. R01 HD05709801, P30 HD062171 and UL1TR000448 to T.E.I.). Additional support came from The Royal Children’s Hospital Foundation devoted to raising funds for research at The Royal Children’s Hospital (Grant No. RCH1000 to J.Y.M.Y.), as well as the Murdoch Children’s Research Institute, the Royal Children’s Hospital, Department of Paediatrics at The University of Melbourne, the Victorian Government’s Operational Infrastructure Support Programme and the United Cerebral Palsy Foundation, The United States (T.E.I.). The funding sources had no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.
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Each author has met the Pediatric Research authorship requirements listed below. All authors (C.E.K., D.K.T., M.C., J.P., T.D.N., J.Y.M.Y., G.B., C.A., A.L.M., J.C., T.E.I., J.L.Y.C., L.W.D., P.J.A.) completed the following: substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; drafting the article or revising it critically for important intellectual content; and final approval of the version to be published.
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Kelly, C.E., Thompson, D.K., Cooper, M. et al. White matter tracts related to memory and emotion in very preterm children. Pediatr Res 89, 1452–1460 (2021). https://doi.org/10.1038/s41390-020-01134-6
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DOI: https://doi.org/10.1038/s41390-020-01134-6
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