White matter microstructure in school-age children with down syndrome
Down syndrome (DS) is the most common genetic cause of intellectual disability, but our understanding of white matter microstructure in children with DS remains limited. Previous studies have reported reductions in white matter integrity, but nearly all studies to date have been conducted in adults or relied solely on diffusion tensor imaging (DTI), which lacks the ability to disentangle underlying properties of white matter organization. This study examined white matter microstructural differences in 7- to 12-year-old children with DS (n = 23), autism (n = 27), and typical development (n = 50) using DTI as well as High Angular Resolution Diffusion Imaging, and Neurite Orientation and Dispersion Imaging. There was a spatially specific pattern of results that showed a dissociation between intra- and inter-hemispheric pathways. Intra-hemispheric pathways (e.g., inferior fronto-occipital fasciculus, superior longitudinal fasciculus) exhibited reduced organization and structural integrity. Inter-hemispheric pathways (e.g., corpus callosum projections) and motor pathways (e.g., corticospinal tract) showed denser neurite packing and lower neurite dispersion. The current findings provide early insight into white matter development in school-aged children with DS and have the potential to further elucidate microstructural differences and inform more targeted clinical trials than what has previously been observed through DTI models alone.
Authors
- Guido Gerig (ORCID: https://orcid.org/0000-0002-9547-6233)
- Natasha Marrus (ORCID: https://orcid.org/0000-0001-6521-0373)
- Juhi Pandey
- Stephen R. Dager (ORCID: https://orcid.org/0000-0002-4034-6087)
- Aimi Salihah Abdul Nasir (ORCID: https://orcid.org/0000-0001-9291-0228)
- Rebecca Grzadzinski (ORCID: https://orcid.org/0000-0001-7764-6166)
- Lonnie Zwaigenbaum (ORCID: https://orcid.org/0000-0001-9607-0799)
- Jason J. Wolff (ORCID: https://orcid.org/0000-0003-4300-8195)
- Mark D. Shen (ORCID: https://orcid.org/0000-0002-1190-7981)
- Khalid Al‐Ali
- Robert T. Schultz
- Tanya St. John (ORCID: https://orcid.org/0000-0003-2448-5797)
- Dea Garic (ORCID: https://orcid.org/0000-0003-3595-4210)
- Robert C. McKinstry (ORCID: https://orcid.org/0000-0003-3578-4899)
- Kelly N Botteron
- Heather C. Hazlett (ORCID: https://orcid.org/0000-0001-9166-1434)
- Martin Andreas Styner (ORCID: https://orcid.org/0000-0002-8747-5118)
- Annette Estes (ORCID: https://orcid.org/0000-0003-2687-4155)
- Chi-Mei Lee (ORCID: https://orcid.org/0000-0001-5983-4729)
- Joseph Piven
- Omar Azrak (ORCID: https://orcid.org/0000-0002-4439-0106)
Institutions
- University of North Carolina at Chapel Hill (US)
- University of Minnesota (US)
- Children's Hospital of Philadelphia (US)
- University of Alberta (CA)
- University of Washington (US)
- Washington University in St. Louis (US)
- Minnesota Department of Education (US)
- University of Washington Medical Center (US)
- Twin Cities Orthopedics (US)
- Mallinckrodt (United States) (US)
- University of Washington Applied Physics Laboratory (US)
- Indiana University – Purdue University Indianapolis (US)
- New York University (US)
Publication Details
- Journal
- Developmental Cognitive Neuroscience
- Published
- 2025-03-01
- DOI
- https://doi.org/10.1016/j.dcn.2025.101540
- Citations
- 3
- Primary Topic
- Advanced Neuroimaging Techniques and Applications
- Type
- article
- Field-Weighted Citation Impact
- 4.08
Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development