# Multifactorial dynamic modeling of brain asymmetry in neurodevelopmental disorders

> **NIH NIH R21** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2024 · $250,607

## Abstract

Project Summary/Abstract Neurodevelopmental disorders (NDDs) comprise of a group of disorders
associated with abnormal brain development, leading to abnormal brain function of language, motor, behavior,
memory and learning. NDDs, e.g., attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder
(ASD) and intellectual disability, affect approximately 15% of children in the United States and pose a
significant public health burden on society. The causes of NDDs are still largely unknown. A growing body of
evidence support that most NDDs are result from a combination of genetic, biological, psychosocial and
environmental risk factors rather than any single origin. Furthermore, there are high rates of co-occurrence
between different NDDs, as well as similarities in functional impairment and clinical features, which make the
diagnosis and treatment of NDDs difficult. Hemispheric asymmetry is a core element of the brain’s usual
organization required for optimal functioning and a key landmark of brain development. We have recently
revealed that brain asymmetry is closely associated with NDDs and their genetic/environmental risk factors
and clinical features, though the causal interacting relationships are unclear. Here we hypothesize that the
biological process of brain asymmetry development is influenced by complex genetic and environmental
contributors for NDDs, and different dysregulations of this multifactorial dynamic system may mediate the
emergence of different clinical symptoms/behaviors in NDDs. Previous studies of brain asymmetry in NDDs
are limited by the case-control and cross-sectional study designs, and the factors contributing to NDDs have
yet to be studied using an integrative method. This proposal seeks to overcome the limitations of previous
studies by applying our novel integrative analytic algorithms and a transdiagnostic approach to several existing
public and internal longitudinal (and cross-sectional) datasets (total N~16,000), which are designed for
studying brain development and related health issues and comprise extensive data of demographics, medical
records, behavioral/clinical assessments, cognitive tests, genetics, and multimodal brain imaging. The
proposed analyses seek to address the following aims: 1) Model the developmental mechanisms of brain
asymmetry involving spatiotemporal interactions between multimodal brain asymmetry components, genetic
and environmental influences and this system’s impact on children behavior/cognition in typically and atypically
developing children and adolescents over time, and 2) characterize within-diagnoses trajectories and cluster
biologically similar participants cutting across conventional diagnostic boundaries to understand both shared
and distinct developmental trajectories of brain asymmetry and behavior/cognition in NDDs. Our study has the
potential to provide definitive neurobiological models of NDDs, with practical implications for helping in
reformulating current di...

## Key facts

- **NIH application ID:** 10888938
- **Project number:** 1R21MH133239-01A1
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Lu Zhao
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $250,607
- **Award type:** 1
- **Project period:** 2024-05-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10888938

## Citation

> US National Institutes of Health, RePORTER application 10888938, Multifactorial dynamic modeling of brain asymmetry in neurodevelopmental disorders (1R21MH133239-01A1). Retrieved via AI Analytics 2026-06-08 from https://api.ai-analytics.org/grant/nih/10888938. Licensed CC0.

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