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

> **NIH NIH P50** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $298,312

## Abstract

Under the diagnostic umbrella of Autism Spectrum Disorder (ASD), tremendous variability is observed across
affected individuals, likely reflecting distinct etiological mechanisms. Yet, most research to date has treated
ASD as a unitary condition, typically comparing individuals with ASD to matched controls. This strategy has not
only hindered our progress in unraveling the neurobiological mechanisms that give rise to ASD
symptomatology but, importantly, such an approach also undermines the potential of translational research to
contribute to `precision medicine' in ASD. In this project, we will take a critical first 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 sample of youth with ASD.
Specifically, we will collect and analyze a rich dataset of brain-based measures (resting-state and task-related
fMRI) of unparalleled resolution and quality in order to characterize individual differences in brain network
properties and examine how these may relate to a rich phenotypic battery of measures tapping into key
domains of interest in our center. Using innovative fMRI activation paradigms as neural assays of social
attention, sensory responsivity, and reward function, we will also examine how patterns of brain responses in
associated neural circuits co-vary within and between individuals in order to determine how neural over-
responsivity to sensory stimuli impacts neural processing of socially relevant stimuli, and assess how distinct
neural endophenotypes of social, sensory, and reward responsivity relate to altered connectivity in functional
brain networks and behavioral phenotypes. Lastly, building upon our prior imaging-genetics studies, we will
examine how polygenic risk, as well as risk variants on selected ASD-associated polymorphisms, influence
brain function, network connectivity, and core ASD symptomatology. Our overarching hypothesis is that both
distinct and shared neuroendophenotypes will be identified based on different brain function and connectivity
metrics and that these will map onto varying dimensions of social and sensory responsivities as manifested at
the behavioral and neural level. We further expect that higher polygenic risk will be predictive of increasingly
aberrant patterns of brain activity and connectivity as well as overall ASD symptom severity, whereas genetic
variance on specific ASD-associated polymorphisms will selectively modulate brain function and network
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 (d) sophisticated data-analytic strat...

## Key facts

- **NIH application ID:** 9984498
- **Project number:** 5P50HD055784-14
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Mirella Dapretto
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $298,312
- **Award type:** 5
- **Project period:** 2007-08-06 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984498

## Citation

> US National Institutes of Health, RePORTER application 9984498, Parsing ASD Heterogeneity: Neuroendophenotypes of Social Attention and Sensory Responsivity (5P50HD055784-14). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9984498. Licensed CC0.

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