FC-SpatialHeterogeneity: Spatial Heterogeneity and Subtypes of Functional Connectivity Development in Youth

This repository contains the official code and scripts used for our study investigating Spatial Heterogeneity and Subtypes of Functional Connectivity (FC) Development in Youth. Our work challenges traditional global brain age metrics by introducing a spatially fine-grained approach to understanding brain maturation.

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✨ Overview

While global brain age metrics offer a general understanding of brain development, they often mask critical local variations. Our research addresses this limitation by introducing a regional brain development (RBD) index, which provides a spatially fine-grained assessment of functional connectivity (FC) maturation across the cortex.

Using functional Magnetic Resonance Imaging (fMRI) data from the Philadelphia Neurodevelopmental Cohort (PNC) for discovery and replicating our findings in the Human Connectome Project Development (HCP-D) cohort, we:

1. Characterized spatial patterns of FC development across the cortex.
2. Identified distinct subtypes of individuals based on their unique spatial FC development patterns using advanced clustering techniques.
3. Demonstrated superior cognitive performance in subtypes reflecting advanced development along the sensorimotor-association axis.
4. Linked these developmental patterns to gene expression profiles that are significantly enriched for neural differentiation, synaptogenesis, and myelination.

This work underscores the critical importance of spatial heterogeneity in gaining a deeper understanding of neurocognitive development.

The code provided in this repository enables users to:

• Calculate the regional development index.
• Replicate the clustering analysis to identify FC development subtypes.
• Explore the intricate links between FC development patterns, cognitive performance, and gene expression profiles.

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📁 Repository Structure & Code Descriptions

This repository is organized into distinct modules, each containing scripts for specific parts of our analysis:

1. regionwise_age_prediction/: Contains scripts for performing region-wise age prediction based on the functional connectivity (FC) profile of each cortical region. This forms the basis for the regional brain development index.

2. regionwise_fc_dev_subtyping/: Includes scripts dedicated to computing the Regional Brain Development (RBD) index maps and subsequently performing the clustering analysis to identify developmental subtypes.

3. gene_association_analysis/: Houses the scripts for conducting association analyses between the derived RBD patterns and relevant gene expression data.

4. replication_hcpd/: Provides scripts specifically designed for the replication analysis of the RBD patterns and subtypes using the independent Human Connectome Project Development (HCP-D) cohort.

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🚀 Getting Started

Detailed instructions for setting up the environment, preparing datasets, and running the code will be provided soon. Please check back for updates!

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📝 Citation

If you find our work useful or inspiring in your research, please cite our study:

@article{li2025spatial,
  title = {Spatial Heterogeneity and Subtypes of Functional Connectivity Development in Youth},
  author = {Li, Hongming and Cui, Zaixu and Cieslak, Matthew and Salo, Taylor and Moore, Tyler M and Gur, Raquel E and Gur, Ruben C and Shinohara, Russell T and Oathes, Desmond J and Davatzikos, Christos and Satterthwaite, Theodore D and Fan, Yong},
  journal = {bioRxiv},
  pages = {2025--01},
  year = {2025},
  publisher = {Cold Spring Harbor Laboratory},
  doi = {[https://doi.org/10.1101/2025.01.24.634828](https://doi.org/10.1101/2025.01.24.634828)}
}

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🙏 Acknowledgment

This project has been generously supported in part by the National Institutes of Health (NIH) through grants U24NS130411 and R01EB022573. We are grateful for their support in making this research possible.