# Brain Network Maturation and Executive Dysfunction Spanning Diagnostic Categories of Psychopathology

> **NIH NIH F31** · UNIVERSITY OF PENNSYLVANIA · 2022 · $34,102

## Abstract

PROJECT SUMMARY
In the healthy brain, white matter connections coordinate the speed and reliability of communication among
spatially distributed regions. The transmission of neural information with fine temporal precision is crucial for
executive function (EF), defined as the coordination of attention, memory, and inhibitory control for goal-directed
actions crucial for survival, health, and well-being. Notably, EF undergoes protracted development throughout
youth, and the development of executive deficits is present in many psychiatric illnesses, including schizophrenia
and ADHD. However, the degree to which transdiagnostic executive deficits arise due to abnormal development
of white matter networks remains unknown. Existing neuroimaging studies of transdiagnostic executive deficits
have been limited by 1) inadequate methods to assess neurodevelopmental patterns of spatially distributed brain
regions, and 2) inadequate theories of neural communication at the level of macro-scale structural networks.
Here we address the latter challenge by generalizing long-established theoretical principles and empirical
observations of efficient neurotransmission at the microscale neuron level to the macroscale structural
connectome by calculating transmission fidelity. Transmission fidelity models how efficiently a brain region
embedded in the structural network can transmit messages to a target region with individually differing speed
and reliability. Moreover, we address the former challenge by capitalizing on advances in network science and
machine learning. Utilizing these methods is a promising direction for investigating abnormal brain development.
In this proposal, we describe the application of a novel analysis of structural network maturation to study the
manifestation of transdiagnostic executive deficits. Using a large sample of youth who completed cross-sectional
neuroimaging as part of the Philadelphia Neurodevelopmental Cohort (n=1,042), our preliminary analyses
demonstrate previously uncharacterized relationships between brain structural connectivity and EF across age.
We will use an additional cross-sectional dataset enriched with youths presenting with psychopathology acquired
through the Healthy Brain Network study (n=5,000) to generalize our findings to executive dysfunction. To
quantify developmental norms, we will capitalize on our large-scale datasets to train a machine learning model
that predicts expected ranges of healthy brain development. Furthermore, understanding within-person changes
in brain structure and EF necessitates longitudinal data. We will longitudinally assess youths diagnosed with
ADHD (n=50) or schizophrenia (n=50), and typically developing comparators (n=40). In this proposal, we aim to
1) delineate how age-related variation of brain network transmission fidelity is associated with executive
dysfunction across psychiatric disorders, and 2) determine how within-individual development in
transmission fidelity is associ...

## Key facts

- **NIH application ID:** 10394757
- **Project number:** 5F31MH126569-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Dale Zhou
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $34,102
- **Award type:** 5
- **Project period:** 2021-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10394757

## Citation

> US National Institutes of Health, RePORTER application 10394757, Brain Network Maturation and Executive Dysfunction Spanning Diagnostic Categories of Psychopathology (5F31MH126569-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10394757. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*