Resting-State fMRI Functional Connectivity: Big Data Preprocessing Pipelines and Topological Data Analysis

Resting-state fMRI measures spontaneous low-frequency fluctuations in the BOLD signal to investigate the functional architecture of the brain. Application of this technique has allowed the identification of various RSNs, or spatially distinct areas of the brain that demonstrate synchronous BOLD fluctuations at rest. Various methods exist for analyzing resting-state data, including seed-based approaches, independent component analysis, graph methods, clustering algorithms, neural networks, and pattern classifiers. Clinical applications of resting-state fMRI are at an early stage of development. However, its use in presurgical planning for patients with brain tumor and epilepsy demonstrates early promise, and the technique may have a future role in providing diagnostic and prognostic information for neurologic and psychiatric diseases.

Resting-state functional magnetic resonance imaging (RFMRI) enables researchers to monitor fluctuations in the spontaneous brain activities of thousands of regions in the human brain simultaneously, representing a popular tool for macro-scale functional connectomics to characterize normal brain function, mind-brain associations, and the various disorders. However, the test-retest reliability of RFMRI remains largely unknown. We review previously published papers on the test-retest reliability of voxel-wise metrics and conduct a meta-summary reliability analysis of seven common brain networks. This analysis revealed that the heteromodal associative (default, control, and attention) networks were mostly reliable across the seven networks. Regarding examined metrics, independent component analysis with dual regression, local functional homogeneity and functional homotopic connectivity were the three mostly reliable RFMRI metrics. These observations can guide the use of reliable metrics and further improvement of test-retest reliability for other metics in functional connectomics. We discuss the main issues with low reliability related to sub-optimal design and the choice of data processing options. Future research should use large-sample test-retest data to rectify both the within-subject and between-subject variability of RFMRI measurements and accelerate the application of functional connectomics.

Brain networks with energy-efficient hubs might support the high cognitive performance of humans and a better understanding of their organization is likely of relevance for studying not only brain development and plasticity but also neuropsychiatric disorders. However, the distribution of hubs in the human brain is largely unknown due to the high computational demands of comprehensive analytical methods. Here we propose a 10(3) times faster method to map the distribution of the local functional connectivity density (lFCD) in the human brain. The robustness of this method was tested in 979 subjects from a large repository of MRI time series collected in resting conditions. Consistently across research sites, a region located in the posterior cingulate/ventral precuneus (BA 23/31) was the area with the highest lFCD, which suggest that this is the most prominent functional hub in the brain. In addition, regions located in the inferior parietal cortex (BA 18) and cuneus (BA 18) had high lFCD. The variability of this pattern across subjects was <36% and within subjects was 12%. The power scaling of the lFCD was consistent across research centers, suggesting that that brain networks have a "scale-free" organization.