# Multiscale statistical testing for connectome-wide association studies in fMRI

**Authors:** P. Bellec, Y. Benhajali, F. Carbonell, C. Dansereau, G. Albouy, M. Pelland, C. Craddock, O. Collignon, J. Doyon, E. Stip, P. Orban  
**arXiv:** [1409.2080](https://arxiv.org/abs/1409.2080)  
**Date:** 2014-09-07  
**Summary page:** https://www.summarizepaper.com/en/paper/1409.2080v2/

## Key points

- The number of brain parcels (or scale) affects the results of a mass univariate general linear model (GLM) in connectome analysis using fMRI.
- Brain parcels used as nodes in connectome analysis were functionally defined by group cluster analysis.
- A classic Benjamini-Hochberg procedure with parametric GLM tests effectively controls the false-discovery rate (FDR) at a given scale.
- Realistic simulations show no substantial inflation of FDR across scales when controlled independently within each scale.
- Rate of discovery varies significantly depending on scales, with higher rates for low scales below 25.
- Statistical maps derived at different scales show consistent results across three real resting-state fMRI datasets (schizophrenia, congenital blindness, motor practice).
- Some specific effects are better observed around scale 50, indicating potential benefits of multiscale analysis.
- Multiscale GLM connectome analysis with FDR captures biologically meaningful effects in various experimental conditions.
- Controlling FDR independently within each scale is important to identify significant associations in fMRI studies across different scales and experimental conditions.

## Summary

This study investigates the impact of the number of brain parcels (or scale) on the results of a mass univariate general linear model (GLM) in connectome analysis using functional magnetic resonance imaging (fMRI). The brain parcels used as nodes in the connectome analysis were functionally defined by a group cluster analysis. The researchers first validate that a classic Benjamini-Hochberg procedure with parametric GLM tests appropriately controls the false-discovery rate (FDR) at a given scale. They then observe through realistic simulations that there is no substantial inflation of the FDR across scales, as long as it is controlled independently within each scale. Furthermore, both simulations and analyses on three real resting-state fMRI datasets (schizophrenia, congenital blindness, motor practice) reveal that the rate of discovery varies significantly depending on scales, with relatively higher rates for low scales below 25. Despite these differences, the statistical maps derived at different scales show consistent results across all three datasets. Some specific effects are better observed around scale 50, highlighting the potential benefits of multiscale analysis. The statistical maps obtained from real data align well with existing literature, supporting the validity of multiscale GLM connectome analysis with FDR in capturing biologically meaningful effects in various experimental conditions. Overall, this study provides valuable insights into how altering brain parcel scale impacts connectome analysis results and highlights the importance of controlling FDR independently within each scale to identify significant associations in fMRI studies across different scales and experimental conditions.