Browsing by Author "Styner, Martin A."

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    Early White Matter Microstructure Alterations in Infants with Down Syndrome
    (medRxiv, 2025-02-27) Azrak, Omar; Garic, Dea; Nasir, Aleeshah; Swanson, Meghan R.; Grzadzinski, Rebecca L.; Al-Ali, Khalid; Shen, Mark D.; Girault, Jessica B.; St. John, Tanya; Pandey, Juhi; Zwaigenbaum, Lonnie; Estes, Annette M.; Wolff, Jason J.; Dager, Stephen R.; Schultz, Robert T.; Evans, Alan C.; Elison, Jed T.; Yacoub, Essa; Kim, Sun Hyung; McKinstry, Robert C.; Gerig, Guido; Pruett, John R., Jr.; Piven, Joseph; Botteron, Kelly N.; Hazlett, Heather; Marrus, Natasha; Styner, Martin A.; Psychiatry, School of Medicine
    Importance: Down syndrome, resulting from trisomy 21, is the most prevalent chromosomal disorder and a leading cause of intellectual disability. Despite its significant impact on brain development, research on the white matter microstructure in infants with Down syndrome remains limited. Objective: To investigate early white matter microstructure in infants with Down syndrome using diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI). Design: Infants were recruited and scanned between March 2019 and May 2024 as participants in prospective studies conducted by the Infant Brain Imaging Study (IBIS) Network. Data were analyzed in October 2024. Setting: Data collection occurred at five research centers in Minnesota, Missouri, North Carolina, Pennsylvania, and Washington. Participants: Down syndrome and control infants were scanned at 6 months of age. Control infants had no Down syndrome diagnosis and either had a typically developing older sibling or, if they had an older sibling with autism, were confirmed not to meet clinical best estimate criteria for an autism diagnosis. Exposure: Diagnosis of Down syndrome. Main outcomes and measures: The outcome of interest was white matter microstructure quantified using DTI and NODDI measures. Results: A total of 49 Down syndrome (28 [57.14%] female) and 37 control (18 [48.65%] female) infants were included. Infants with Down syndrome showed significant reductions in fractional anisotropy and neurite density index across multiple association tracts, particularly in the inferior fronto-occipital fasciculus and superior longitudinal fasciculus II, consistent with reduced structural integrity and neurite density. These tracts also demonstrated increased radial diffusivity, suggesting delayed myelination. The inferior fronto-occipital fasciculus and uncinate fasciculus exhibited increased neurite dispersion and fanning in Down syndrome infants, reflected by elevated orientation dispersion index. Notably, the optic tracts in Down syndrome infants exhibited a distinct pattern of elevated fractional anisotropy and axial diffusivity, and lower radial diffusivity and orientation dispersion index, suggesting an early maturation of these pathways. Conclusions and relevance: This first characterization of white matter microstructure in Down syndrome infants reveals widespread white matter developmental delays. These findings provide new insights into the early neurodevelopment of Down syndrome and may inform early therapeutic interventions.
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    Maternal choline supplementation in a sheep model of first trimester binge alcohol fails to protect against brain volume reductions in peripubertal lambs
    (Elsevier, 2016-09) Birch, Sharla M.; Lenox, Mark W.; Kornegay, Joe N.; Paniagua, Beatriz; Styner, Martin A.; Goodlett, Charles R.; Cudd, Tim A.; Washburn, Shannon E.; Psychology, School of Science
    Fetal alcohol spectrum disorder (FASD) is a leading potentially preventable birth defect. Poor nutrition may contribute to adverse developmental outcomes of prenatal alcohol exposure, and supplementation of essential micronutrients such as choline has shown benefit in rodent models. The sheep model of first-trimester binge alcohol exposure was used in this study to model the dose of maternal choline supplementation used in an ongoing prospective clinical trial involving pregnancies at risk for FASD. Primary outcome measures included volumetrics of the whole brain, cerebellum, and pituitary derived from magnetic resonance imaging (MRI) in 6-month-old lambs, testing the hypothesis that alcohol-exposed lambs would have brain volume reductions that would be ameliorated by maternal choline supplementation. Pregnant sheep were randomly assigned to one of five groups – heavy binge alcohol (HBA; 2.5 g/kg/treatment ethanol), heavy binge alcohol plus choline supplementation (HBC; 2.5 g/kg/treatment ethanol and 10 mg/kg/day choline), saline control (SC), saline control plus choline supplementation (SCC; 10 mg/kg/day choline), and normal control (NC). Ewes were given intravenous alcohol (HBA, HBC; mean peak BACs of ~280 mg/dL) or saline (SC, SCC) on three consecutive days per week from gestation day (GD) 4–41; choline was administered on GD 4–148. MRI scans of lamb brains were performed postnatally on day 182. Lambs from both alcohol groups (with or without choline) showed significant reductions in total brain volume; cerebellar and pituitary volumes were not significantly affected. This is the first report of MRI-derived volumetric brain reductions in a sheep model of FASD following binge-like alcohol exposure during the first trimester. These results also indicate that maternal choline supplementation comparable to doses in human studies fails to prevent brain volume reductions typically induced by first-trimester binge alcohol exposure. Future analyses will assess behavioral outcomes along with regional brain and neurohistological measures.