Frequency Specificity of Regional Homogeneity in the Resting-State Human Brain

<div><p>Resting state-fMRI studies have found that the inter-areal correlations in cortical networks concentrate within ultra-low frequencies (0.01–0.04 Hz) while long-distance connections within subcortical networks distribute over a wider frequency range (0.01–0.14 Hz). However, the frequency characteristics of regional homogeneity (ReHo) in different areas are still unclear. To examine the ReHo properties in different frequency bands, a data-driven method, Empirical Mode Decomposition (EMD), was adopted to decompose the time series of each voxel into several components with distinct frequency bands. ReHo values in each of the components were then calculated. Our results showed that ReHo in cortical areas were higher and more frequency-dependent than those in the subcortical regions. BOLD oscillations of 0.02–0.04 Hz mainly contributed to the cortical ReHo, whereas the ReHo in limbic areas involved a wider frequency range and were dominated by higher-frequency BOLD oscillations (>0.08 Hz). The frequency characteristics of ReHo are distinct between different parts of the striatum, with the frequency band of 0.04–0.1 Hz contributing the most to ReHo in caudate nucleus, and oscillations lower than 0.02 Hz contributing more to ReHo in putamen. The distinct frequency-specific ReHo properties of different brain areas may arise from the assorted cytoarchitecture or synaptic types in these areas. Our work may advance the understanding of the neural-physiological basis of local BOLD activities and the functional specificity of different brain regions.</p></div

Result of k-means clustering.

<p>Voxels with similar frequency-specific ReHo characteristics were automatically classified into the same cluster. Different clusters are coded with different colors. Certain canonical cortical regions (networks) are identified and labeled include: posterior cingulate cortex (PCC)/precuneus, bilateral inferior parietal lobule (IPL), lateral prefrontal cortex (LPFC), primary visual area (V1), higher-order visual network (hVIN).</p

Frequency properties of IMFs.

<p>The histograms of HWF of IMF1 to IMF5 (color-coded by red, yellow, green, cyan and blue respectively) were determined from all the voxels in the whole brains across all the 198 subjects. Heights of the histograms represent the number of voxels whose HWF equals that frequency on the horizontal axis.</p

F-map (Q<0.001, FDR corrected) representing brain areas whose ReHo are significantly frequency-dependent.

<p>Key brain areas survived the FDR correction are marked with a circle and the names (abbreviations) of these areas are indicated beside the circle. Abbreviations: posterior cingulate cortex (PCC)/precuneus, bilateral inferior parietal lobule (IPL), lateral prefrontal cortex (LPFC), primary visual area (V1), higher-order visual network (hVIN), sensory motor network (SMN), and white matter (WM).</p

The statistics of the cancer datasets used in this study.

The statistics of the cancer datasets used in this study.</p

An illustration of the proposed framework.

The biological process activity of each sample is obtained by core genes regression and used as the outcome of the casual model. The casual model consists of an inference network to calculate the mean and variance of P(Z|X,y,m) and a model network to recover P(Z,X,y,m).</p

Top 10 mutations with the highest causal effect on DNA replication in 10 cancers.

The figure shows the ATE value and the mutation rate of each predicted key mutation.</p

S1 Text -

Section A. Comparison with other methods for discovering single driver mutation. Section B. Parameters analysis of CEBP. Section C. Selection of core genes in CEBP. Table A in S1 Text. The causal effect of TP53 mutation on DNA replication and EMT of BRCA under different numbers of hidden confounders settings. Table B in S1 Text. The causal effect of TP53 mutation on DNA replication and EMT of LUAD under different numbers of hidden confounders settings. Fig A in S1 Text. Fraction of predicted driver genes presents in CGC which consists 616 cancer-related mutations. Fig B in S1 Text. Heat maps of correlations between genes of DNA replication and EMT in BRCA, LUAD, and LIHC tumor samples, where the color indicates the correlation value and the number on the horizontal and vertical axes is the gene’s index. (DOCX)</p

Top 10 mutations with the highest causal effect on EMT process in 10 cancers.

The figure shows the ATE value and the mutation rate of each predicted key mutation.</p

The Mann-Whitney U test (M.W.) analysis shows there is no significant differences between mutated groups and non-mutated groups of mutated genes with high mutation rates in the activity of DNA replication (DR) for 10 cancers.

The Mann-Whitney U test (M.W.) analysis shows there is no significant differences between mutated groups and non-mutated groups of mutated genes with high mutation rates in the activity of DNA replication (DR) for 10 cancers.</p