# Neural Substrates of Autism and ADHD: Reward Circuitry Connectivity and Individual Differences

> **NIH NIH K01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2024 · $183,854

## Abstract

PROJECT SUMMARY/ABSTRACT
Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) exhibit significant clinical
overlap, but the shared and distinct biology of these conditions remains incompletely understood. Both ASD and
ADHD have been linked in part to the brain’s reward system, with prior work demonstrating that these conditions
are associated with altered function and structure of individual reward structures. However, reward areas do not
act in isolation but instead communicate extensively with many higher- and lower-order brain regions, including
sensorimotor and cognitive control areas implicated in ASD and ADHD, respectively. To inform our
understanding of the convergent and divergent neural mechanisms underlying ASD and ADHD, there is thus a
crucial need to understand how the connectivity patterns of reward structures are altered in these conditions.
The proposed project will use cutting-edge resting-state functional magnetic resonance imaging (rsfMRI)
methods together with refined machine learning and statistical modeling approaches to investigate reward
functional connectivity in ASD and ADHD. Analyses will consider both categorical diagnoses (ASD, ADHD,
comorbid ASD+ADHD, neurotypical controls) and continuous ASD and ADHD symptoms across the population.
Datasets will include the largest available samples in the world for both categorical diagnoses (N>6,000; ages
5-65) and continuous symptoms (N>11,000; ages 9-14). The aims of this project are as follows: Aim 1 will
investigate the functional connectivity patterns of reward regions in ASD and ADHD using machine learning and
multivariate statistical approaches. Aim 2 will assess the moderating impact of key sources of heterogeneity
(sex, puberty, medication) on reward functional connectivity in ASD and ADHD using machine learning. Aim 3
will create normative reference curves of reward functional connectivity using data-driven modeling approaches
and examine deviations from typical maturational trajectories in ASD and ADHD. Taken together, this work will
substantially improve our understanding of reward circuitry in ASD and ADHD, as well as the shared and distinct
neural underpinnings of these conditions. In the long-term, this project will contribute to the development and
personalization of novel biologically-grounded treatments for ASD and ADHD. These studies are in line with the
NIMH strategic plan to define the brain mechanisms underlying complex behaviors, and to examine mental
illness trajectories across the lifespan. Additionally, this proposal will provide the PI with significant training in the
following new areas: (1) refined machine learning methods, (2) advanced statistical modeling approaches, and
(3) cutting-edge functional connectivity methods. This training will be completed under the mentorship of Drs.
Paul Thompson, Jose-Luis Ambite and Vince Calhoun, who are world-renowned experts in their respective fields.
As a whole, the proposed research ...

## Key facts

- **NIH application ID:** 11054459
- **Project number:** 1K01MH135160-01A1
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Katherine E Lawrence
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $183,854
- **Award type:** 1
- **Project period:** 2024-09-03 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11054459

## Citation

> US National Institutes of Health, RePORTER application 11054459, Neural Substrates of Autism and ADHD: Reward Circuitry Connectivity and Individual Differences (1K01MH135160-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11054459. Licensed CC0.

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