# Neural signatures of outcome in preschoolers with autism

> **NIH NIH R01** · CHILD MIND INSTITUTE, INC. · 2021 · $697,991

## Abstract

Objective. This proposal has the important goal of furthering our understanding of the longitudinal course of
autism spectrum disorder (ASD). It is motivated by the urgent need for early prognostic markers able to explain
the extensive heterogeneity of ASD outcomes. To this end, we propose a longitudinal study of young children
with ASD (2-3 years) to identify the neurobiological underpinnings of early developmental changes in restricted
repetitive behavior/interests (RRB) – one of the most clinically impairing aspects of ASD - and their predictive
contribution to later function. The proposal builds on the confluence of related findings and our own work
including: 1) clinical evidence that RRB changes over the age window between ~29 and 42 months are
prognostic markers of ASD adult functioning; and 2) advances in brain developmental functional connectomics
that allow investigations of neural circuits in preschoolers with ASD using natural sleep MRI. We specifically aim
to test 1) whether changes from 24-36 to 36-48 months-of-age (T1, T2) in the intrinsic functional connectivity
(iFC) of somatomotor (SM) striatal-cortical circuitry are associated with changes in the repetitive sensory motor
(RSM) subdomain of RRB; and 2) whether these early brain-behavioral changes predict later (age: 48-60
months, T3) adaptive functioning. Exploratory aims will examine the potential contributions of structural
connectivity changes in striatal-cortical tracts, and test whole-brain iFC employing unbiased connectome-wide
association. Finally, we will explore the value of an alternative, data-driven hierarchical clustering approach to
characterizing outcomes based upon multiple clinical dimensions at T3. Methods. We anticipate obtaining
complete T1 and T2 brain-behavioral data from 100 preschoolers with ASD enrolled at age 24-36 months and
followed prospectively on a yearly basis. At T1 and T2, preschoolers will undergo natural sleep imaging with
state-of-the-art MRI (high resolution T1- and T2-weighted structural MRI, multiband resting state fMRI (R-
fMRI), and when possible, diffusion tensor) and phenotypic assessments rigorously selected to deeply
phenotype a range of ASD core and associated symptoms. To examine the predictive value of iFC and RSM
changes (i.e., T1-T2) to later function, children will be re-evaluated at 48-60 months (T3). A partial list of
assessments includes: Autism Diagnostic Observation Schedule-2, Behavioral Observation Social
Communication Checklist, Repetitive Behavior Scale-Revised, clinician and parent measures of comorbid
psychopathology and adaptive functioning. Brain-behavior analyses will primarily rely on R-fMRI, and explore
diffusion tensor imaging. Significance. Findings will elucidate the neural correlates of changes in RSM at the
earliest practical time following clinical diagnosis. They will provide a developmentally informed understanding
of the neural underpinnings of outcomes, thus bringing the field closer to a neural strati...

## Key facts

- **NIH application ID:** 10203750
- **Project number:** 5R01MH115363-04
- **Recipient organization:** CHILD MIND INSTITUTE, INC.
- **Principal Investigator:** Adriana Di Martino
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $697,991
- **Award type:** 5
- **Project period:** 2018-08-21 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10203750

## Citation

> US National Institutes of Health, RePORTER application 10203750, Neural signatures of outcome in preschoolers with autism (5R01MH115363-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10203750. Licensed CC0.

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