HINT: A hierarchical independent component analysis toolbox for investigating brain functional networks using neuroimaging data

Abstract

Background: Independent component analysis (ICA) is a popular tool for investigating brain organization in neuroscience research. In fMRI studies, an important goal is to study how brain networks are modulated by subjects' clinical and demographic variables. Existing ICA methods and toolboxes don't incorporate subjects' covariates effects in ICA estimation of brain networks, which potentially leads to loss in accuracy and statistical power in detecting brain network differences between subjects' groups.

New method: We introduce a Matlab toolbox, HINT (Hierarchical INdependent component analysis Toolbox), that provides a hierarchical covariate-adjusted ICA (hc-ICA) for modeling and testing covariate effects and generates model-based estimates of brain networks on both the population- and individual-level. HINT provides a user-friendly Matlab GUI that allows users to easily load images, specify covariate effects, monitor model estimation via an EM algorithm, specify hypothesis tests, and visualize results. HINT also has a command line interface which allows users to conveniently run and reproduce the analysis with a script.

Comparison to existing methods: HINT implements a new multi-level probabilistic ICA model for group ICA. It provides a statistically principled ICA modeling framework for investigating covariate effects on brain networks. HINT can also generate and visualize model-based network estimates for user-specified subject groups, which greatly facilitates group comparisons.

Results: We demonstrate the steps and functionality of HINT with an fMRI example data to estimate treatment effects on brain networks while controlling for other covariates. Results demonstrate estimated brain networks and model-based comparisons between the treatment and control groups. In comparisons using synthetic fMRI data, HINT shows desirable statistical power in detecting group differences in networks especially in small sample sizes, while maintaining a low false positive rate. HINT also demonstrates similar or increased accuracy in reconstructing both population- and individual-level source signal maps as compared to some state-of-the-art group ICA methods.

Conclusion: HINT can provide a useful tool for both statistical and neuroscience researchers to evaluate and test differences in brain networks between subject groups.

Keywords: Brain network; Covariate effects; Hierarchical model; Independent component analysis (ICA); Matlab; fMRI.