# Parsing ASD Heterogeneity: Neuroendophenotypes of Social Attention and Sensory Responsivity

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $729,121

## Abstract

PROJECT DESCRIPTION
Despite the tremendous variability observed across individuals diagnosed with Autism Spectrum Disorder
(ASD), most research to date has treated ASD as a unitary condition, comparing individuals with ASD to
neurotypical controls. This approach has hindered our progress in unraveling the neurobiological mechanisms
that give rise to ASD symptomatology and it also undermines the potential of translational research to
contribute to `precision medicine' in ASD. In this project, we take a critical step toward dissecting the significant
heterogeneity observed in ASD by combining state-of-the-art imaging methods, novel approaches to account
for genetic susceptibility, and a deep phenotypic characterization of a large and unique sample of males and
females with ASD that we curated as part of our recently renewed ACE Network (MH100028). Capitalizing on
the comprehensive assays already collected in this cohort (i.e., phenotyping, genotyping, MRI, EEG) and our
involvement in the Human Connectome Project - Development (MH109589), here we will collect and analyze a
rich dataset of brain-based measures of unparalleled resolution and quality in order to characterize individual
differences in brain network properties and examine how these relate to a vast phenotypic battery of measures
tapping into key domains of interest. Using resting-state fMRI and innovative fMRI activation tasks as neural
assays of social and sensory responsivity, we will examine how functional connectivity and brain responses in
associated neural circuits co-vary within and between individuals in order to determine how atypical reactivity
to sensory stimuli impacts neural processing of socially relevant stimuli, and assess how distinct neural
endophenotypes of social and sensory responsivity relate to altered functional connectivity and behavioral
phenotypes. Building upon our prior imaging-genetics work, we will also examine how polygenic risk, and risk
genetic variants on ASD-associated polymorphisms, influence brain function, connectivity, as well as core ASD
symptoms. Our overarching hypothesis is that both distinct and shared neuroendophenotypes will be identified
across our sample based on different brain function and connectivity metrics and that these will map onto
varying dimensions of social and sensory atypicalities manifested at the neural and behavioral level. We further
expect that higher polygenic risk will predict increasingly aberrant patterns of brain activity, connectivity, and
overall symptom severity, whereas genetic variance on ASD-associated polymorphisms will selectively
modulate brain function and connectivity in brain circuits where these ASD risk genes are expressed. By
employing (a) cutting-edge imaging methods to examine brain function and connectivity, (b) innovative
paradigms to relate social attention and motivation to sensory processing atypicalities, (c) novel approaches to
integrate genetic risk with neural and behavioral phenotypes, and...

## Key facts

- **NIH application ID:** 9970246
- **Project number:** 5R01MH117982-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Mirella Dapretto
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $729,121
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9970246

## Citation

> US National Institutes of Health, RePORTER application 9970246, Parsing ASD Heterogeneity: Neuroendophenotypes of Social Attention and Sensory Responsivity (5R01MH117982-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9970246. Licensed CC0.

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