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

Frequency-Dependent Modulation of Regional Synchrony in the Human Brain by Eyes Open and Eyes Closed Resting-States

<div><p>The eyes-open (EO) and eyes-closed (EC) states have differential effects on BOLD-fMRI signal dynamics, affecting both the BOLD oscillation frequency of a single voxel and the regional homogeneity (ReHo) of several neighboring voxels. To explore how the two resting-states modulate the local synchrony through different frequency bands, we decomposed the time series of each voxel into several components that fell into distinct frequency bands. The ReHo in each of the bands was calculated and compared between the EO and EC conditions. The cross-voxel correlations between the mean frequency and the overall ReHo of each voxel’s original BOLD series in different brain areas were also calculated and compared between the two states. Compared with the EC state, ReHo decreased with EO in a wide frequency band of 0.01–0.25 Hz in the bilateral thalamus, sensorimotor network, and superior temporal gyrus, while ReHo increased significantly in the band of 0–0.01 Hz in the primary visual cortex, and in a higher frequency band of 0.02–0.1 Hz in the higher order visual areas. The cross-voxel correlations between the frequency and overall ReHo were negative in all the brain areas but varied from region to region. These correlations were stronger with EO in the visual network and the default mode network. Our results suggested that different frequency bands of ReHo showed different sensitivity to the modulation of EO-EC states. The better spatial consistency between the frequency and overall ReHo maps indicated that the brain might adopt a stricter frequency-dependent configuration with EO than with EC.</p></div

Histograms of the whole-brain <i>Freq</i> distribution across patients with mTLE and healthy controls.

<p>The histograms are measured only for gray matter voxels in the entire brain and averaged across all the subjects in each group. Height of the histograms represents the number of voxels whose <i>Freq</i> is equal to the frequency on the horizontal axis. The healthy controls, patients with left mTLE and those with right mTLE are color-coded by black, red and blue, respectively.</p

Mean <i>Freq</i> Values and Standard Deviation of the Bilateral Hippocampus and the Results of Significance Test for Healthy Controls and Patients with mTLE.

<p>Mean <i>Freq</i> Values and Standard Deviation of the Bilateral Hippocampus and the Results of Significance Test for Healthy Controls and Patients with mTLE.</p

Histograms of the <i>Freq</i> distribution of the unilateral hippocampus across patients with mTLE and healthy controls.

<p>The healthy controls, patients with left mTLE and those with right mTLE are color-coded by black, red and blue, respectively. (A) left hippocampus. (B) right hippocampus. The histograms are measured only for gray matter voxels and averaged across subjects in each group. Height of the histograms represents the number of voxels whose <i>Freq</i> equals the frequency on the horizontal axis.</p

Results of the one sample <i>t</i>-test for <i>Freq</i> map across the three groups.

<p>(A) healthy controls. (B) patients with left mTLE. (C) patients with right mTLE. One sample <i>t</i>-test, <i>p</i> < 0.05, voxels > 80, with FDR correction (<i>Q</i> value < 0.01). Color scale indicates the high <i>Freq</i> value.</p

Statistical <i>T</i>-map showing the differences in the bilateral hippocampus between patients with mTLE and healthy controls.

<p>Results of the two sample <i>t</i>-test without correction. (A) and (B) Comparison of <i>Freq</i> in the bilateral hippocampus between patients with left mTLE and controls; (C) and (D) Comparison of <i>Freq</i> in the bilateral hippocampus between patients with right mTLE and controls. The meanings of colors are the same to those in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0157342#pone.0157342.g003" target="_blank">Fig 3</a>.</p