Introduction
The aim of this study was to examine topological properties of intrinsic functional brain networks in the individuals with mild traumatic brain injury (mTBI), particularly during subacute phase of injury (<=1 month). The relationship between intrinsic functional network characteristics and cognitive performance was also investigated to determine what brain changes were associated with cognitive function after injury.
Methods
Resting-state functional magnetic resonance imaging data (3T Siemens scanner) were acquired from 31 individuals with mTBI (mean age, 45.5 ± 15.5 years) and 23 controls (mean age, 41.0 ± 12.2 years). All individuals completed cognitive tasks assessed by the Computerized NeuroCognitive Function Test (CNT40®; MaxMedica, Seoul, Korea). After preprocessing the data, functional connectivity of each individual was constructed. Nodes were defined by a set of regions of interest (ROIs) from the automated anatomical labeling template, except the bilateral olfactory and rectus areas due to signal susceptibility artifacts. Edges were defined by a correlation coefficient between the averaged time-series data of a pair of ROIs. A positive correlation matrix was constructed across 112 nodes after age and gender were removed from the data using the general linear model, and thresholded considering the sparsity of the matrix (the number of edges was the same between individuals, the size of the connected components was the largest). The characteristics of the network were examined by betweenness centrality (BC), strength (STR), clustering coefficient (CC), local efficiency (Eloc), and global efficiency (Eglob), using the Brain Connectivity Toolbox. Between group comparison was performed by a non-parametric permutation test (P<0.05). The cognitive function was correlated with the graph-theory measures by Pearson’s correlation analysis.
Results
In comparison to the controls, the mTBI group showed a tendency toward reduced Eglob, BC, and STR, and showed a significantly reduced CC and Eloc at a global level (Fig1). At the nodal perspective, we observed both decreased and increased BC and STR, and only observed decreased CC and Eloc in several brain areas, which are relevant to dysfunctional activation after mTBI or in areas that are part of the default mode network (Fig2).
The STR of the right parahippocampus and left hippocampus showed a significant and positive correlation with the cognitive scores of the visual delayed recall test. The test scores were not significantly different between the groups and the positive correlation was only observed in the mTBI group (Fig3).
Conclusion
The changes in network characteristics observed in the mTBI group reflect reduced centrality and segregation, and inefficient processing of the network. The positive correlation observed between the cognitive scores and the network characteristics indicates that even subtle cognitive changes are accompanied by network reorganization. |
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The results of group comparisons between the global network characteristics including (a) global efficiency (Eglob), (b) betweenness centrality (BC), (c) strength (STR), (d) clustering coefficient (CC), and (e) local efficiency (Eloc). In the five box plots, the central marks displayed by a red line indicated the median, and the bottom and top edges of the boxes indicated 25th and 75th percentiles, respectively. The whiskers were from the ends of the interquartile ranges to the furthest observation of 1.5 times the interquartile ranges. Any other observations above the range were displayed with a red + sign. From the one-sided two-sample t-test, only the CC and Eloc showed significant group differences (Eglob, p=0.0539; BC, p=0.0564; STR, p=0.0530; CC, p=0.0406, and Eloc, p=0.0425, respectively). The results of non-parametric random permutation tests for CC (f), and Eloc (g) also proved the significant results of the group comparisons. The red line in the (f) and (g) showed the averaged 5th percentiles of the null distribution of CC and Eloc in each node, and the black line showed the averaged t-values of the comparison of each node between the groups.
The results of group comparison on the nodal characteristics of network including (a) betweenness centrality (BC), (b) strength (STR), (c) clustering coefficient (CC), and (d) local efficiency (Eloc), which were displayed on bar graph. The color of each bar was determined by the location of the brain as follows; the dark red indicated that the corresponding node was included in the frontal lobe. The yellow indicated limbic areas, green indicated parietal lobe, light blue indicated temporal lobe, pink indicated occipital lobe, and the gray indicated the cerebellum. The black solid line on the bar indicated averaged value of the all 112 nodes over all individuals of each group, while the black dashed line on the bar indicated one standard deviation above and below the averaged value of each node over all individuals of each group, respectively. The increased and decreased nodal characteristics in the mild traumatic brain injury (mTBI) group compared to the controls were defined with blue and red arrows, respectively. The name of the regions showing the significantly increased network characteristics were listed on the bar graph with a red color while the significantly decreased network characteristics were listed on the bar graph with a blue color. The significance of the group comparison was set at p<0.05 in the non-parametric random permutation test.
The relationship between the network characteristics and cognitive performance in the mild traumatic brain injury (mTBI) and control groups. (a) The strength of the right parahippocampal area in the mTBI group showed a significantly positive correlation with the scores of visual delayed recall test (r=0.6249, p<0.0005), while (b) those in the control group showed no association with the scores of visual delayed recall test (r=-0.2652, p=0.2213). (c) The strength of the left hippocampus in the mTBI group showed a significantly positive correlation with the scores of visual delayed recall test (r=0.6318, p<0.0005), while (d) those in the control group showed no association with the scores of visual delayed recall test (r=0.0043, p=0.9843). Blue dots indicated individuals of mTBI, and back dots indicated control subjects.
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