Abstract

Functional connectivity analysis using resting-state functional magnetic resonance imaging (rs-fMRI) has emerged as a powerful technique for investigating functional brain networks. The functional connectivity is often quantified by statistical metrics (e.g., Pearson correlation coefficient), which may be affected by many image acquisition and preprocessing steps such as the head motion correction and the global signal regression. The appropriate quantification of the connectivity metrics is essential for meaningful and reproducible scientific findings. We propose a novel empirical Bayes method to normalize the functional brain connectivity metrics on a posterior probability scale. Moreover, the normalization function maps the original connectivity metrics to values between zero and one, which is well-suited for the graph theory based network analysis and avoids the information loss due to the (negative value) hard thresholding step. We apply the normalization method to a simulation study and the simulation results show that our normalization method effectively improves the robustness and reliability of the quantification of brain functional connectivity and provides more powerful group difference (biomarkers) detection. We illustrate our method on an analysis of a rs-fMRI dataset from the Autism Brain Imaging Data Exchange (ABIDE) study.

Highlights

  • Resting-state fMRI has been applied to study functional brain connectivity patterns and networks in the absence of external stimuli (Biswal et al, 1995; Beckmann et al, 2005; Fransson, 2005; De Luca et al, 2006; Fox et al, 2006)

  • As the direct assessment of the normalization effect on connectivity metrics could be challenging, we examine the normalization method by comparing the statistical inferences based on normalized connectivity metrics and raw connectivity metrics

  • We focus on the differential connectivity expressions between TC and Autism spectrum disorders (ASD) by using normalized connectivity metrics

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Summary

Introduction

Resting-state fMRI (rs-fMRI) has been applied to study functional brain connectivity patterns and networks in the absence of external stimuli (Biswal et al, 1995; Beckmann et al, 2005; Fransson, 2005; De Luca et al, 2006; Fox et al, 2006). Many previous rs-fMRI studies have identified altered functional connectivity expressions and networks from different clinical populations (Dosenbach et al, 2007; Greicius, 2008; Fornito et al, 2012). The functional connectivity analyses are often conducted based on connectivity metrics rather than the raw time courses from rs-fMRI data. The functional connectivity strength is often quantified by a calculated statistic (most times a scalar), and the reproducibility and validity of the following group level statistical inferences are heavily impacted by the statistical

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