# Brain Development in Down Syndrome during Fetal, Newborn, and Infant Stages

> **NIH NIH R21** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $54,126

## Abstract

Abstract
Down syndrome (DS), known as trisomy 21, is the most common chromosomal disorder in newborns. The
number of babies born with DS is increasing, with about 1 in every 700 babies being born with DS in the United
States (US). Patients with DS carry an extra complete or partial chromosome 21, disrupting numerous
processes, including cardiac, digestive, and neural systems, with cognitive impairment being one of the most
notable features. Patients with DS have problems with learning, memory, and speech/language throughout life,
as well as an early onset of Alzheimer’s disease. Given that DS patients live longer than before as a result of
improved medical care, and in view of the fact that the concept of locus minoris resistentiae is still valid, it is
critical to study the altered initial states of brain development in DS for the purpose of better predicting what
aspects of brain function will preferentially and precociously deteriorate; this would allow for earlier and better
prevention and treatment. However, detailed, comprehensive knowledge of early development of cortical
anatomy and fiber pathways in DS patients is still lacking. The brain abnormalities in DS begin in utero; fewer
neurons are generated and migrate to wrong destinations. By 15 gestational weeks (GW), brains with DS have
abnormal cortical thickness, with volumes that are 80% of those of typically developing brains. However, much
more detailed information is needed, and we now have the tools to make direct anatomical observation on fetal
and early postnatal DS brains. We have extensive experience, both in ex vivo and in vivo, magnetic
resonance imaging (MRI) of human brains. We have established that high-angular resolution diffusion MRI
(HARDI) with optimal parameters has the potential to define the connectional anatomy of developing human
fetal, newborn, and infant brains. We have reported, with unprecedented details, spatiotemporal developmental
patterns of the majority of axonal tracts, as well as regional regression patterns of neuronal migration pathways
using diffusion MRI tractography. In fetal ages, transient zones (e.g., future cortical gray matter, cortical plate
[CP]; future white matter, intermediate zone [IZ]) continuously change their morphology, reflecting neuronal
proliferation/migration, and axonal elongation, maturation, and pruning, and could provide critical biomarkers for
normal/abnormal brain development. Through recent preliminary MRI investigations in typically developing
brains, we have observed migration and axonal pathways terminating in different transient zones, not randomly
but with unique spatiotemporal patterns. Based on the demonstrated anomalies in the gross morphology of the
DS brain, together with what is already known about metric changes in the cortex and white matter, we
hypothesize that early brain development in DS will show regionally differential spatiotemporal patterns as
compared to that in controls.

## Key facts

- **NIH application ID:** 10507226
- **Project number:** 7R21HD098606-03
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Emi Takahashi (Oki)
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $54,126
- **Award type:** 7
- **Project period:** 2021-11-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10507226

## Citation

> US National Institutes of Health, RePORTER application 10507226, Brain Development in Down Syndrome during Fetal, Newborn, and Infant Stages (7R21HD098606-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10507226. Licensed CC0.

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