# Cellular, molecular, and functional imaging approaches to understanding early neurodevelopment in autism

> **NIH NIH P50** · YALE UNIVERSITY · 2020 · $2,162,500

## Abstract

The Yale Center represents a multidisciplinary research program consisting of five inter-related research
projects and four cores dedicated to advancing understanding of early neurobiology of ASD. The proposal
brings together a team of experts from the fields of developmental psychopathology and neurobiology,
genetics, neurology, radiology, neuroscience, and statistics to identify the molecular, cellular, and neural
mechanisms related to ASD from prenatal stages to childhood. We focus our investigation on two cohorts of
younger siblings of children with ASD who, due to familial factors, are at high risk (HR) for developing the
disorder: a prospective cohort recruited pre- and perinatally and followed through 24 months, and a cohort of
HR siblings who was well-characterized at 24 months through our past studies and will reach the age of 12
years during the life of the Yale ACE. These cohorts enable our search for neural signatures of ASD during
fetal, neonatal, and school-age periods, as well as to examine the connectome across the spectrum of risk for
ASD both in males and females. Although neural and behavioral markers of ASD have been reported in 6-
month-old infants later diagnosed with ASD, to our best knowledge, this is the first investigation into both fetal
and neonatal functional connectivity in ASD. Emerging data suggest that male, but not female, ASD subjects
demonstrate significant alterations in neural networks, and – for the first time – the proposed studies will
identify not only the changes in connectivity in ASD but also the impact of fetal/neonatal sex upon these
changes. Since recent studies demonstrate neuroplasticity in the developing brain across the late second and
third trimesters of gestation, it is essential to understand if the factors associated with ASD are developing in
this same time frame and to understand any sex differences that may be apparent even at that early age. The
iPSC derived organoid system models human fetal development, allowing us to investigate neurobiological risk
and protective factors that play a unique role in this period and may enable the discovery of patient-specific
neuronal or stem cell biomarkers that could be used as predictors of risk or resilience in ASD. The Yale ACE
aims rely on application of cutting-edge approaches to the analysis the connectome, fetal and neonatal
imaging modeling neural development using the iPSC methodology with high resolution dual photon imaging
approaches, the development of early markers for ASD, studying early attention and learning, novel predictive
models relating brain organization to behavior, and statistical approaches for integrating the spectrum of data
types across to address these aims. Results from the combined projects have a great potential to identify novel
diagnostic and prognostic markers at the time of birth, identify neural, cellular, and molecular bases of risk and
protective mechanisms in ASD, and clarify neural bases of sex differences in ...

## Key facts

- **NIH application ID:** 9999037
- **Project number:** 5P50MH115716-04
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** KATARZYNA CHAWARSKA
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,162,500
- **Award type:** 5
- **Project period:** 2017-09-07 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9999037

## Citation

> US National Institutes of Health, RePORTER application 9999037, Cellular, molecular, and functional imaging approaches to understanding early neurodevelopment in autism (5P50MH115716-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9999037. Licensed CC0.

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