Abnormal cortical networks in mild cognitive impairment and Alzheimer's disease - PubMed (original) (raw)
Abnormal cortical networks in mild cognitive impairment and Alzheimer's disease
Zhijun Yao et al. PLoS Comput Biol. 2010.
Abstract
Recently, many researchers have used graph theory to study the aberrant brain structures in Alzheimer's disease (AD) and have made great progress. However, the characteristics of the cortical network in Mild Cognitive Impairment (MCI) are still largely unexplored. In this study, the gray matter volumes obtained from magnetic resonance imaging (MRI) for all brain regions except the cerebellum were parcellated into 90 areas using the automated anatomical labeling (AAL) template to construct cortical networks for 98 normal controls (NCs), 113 MCIs and 91 ADs. The measurements of the network properties were calculated for each of the three groups respectively. We found that all three cortical networks exhibited small-world properties and those strong interhemispheric correlations existed between bilaterally homologous regions. Among the three cortical networks, we found the greatest clustering coefficient and the longest absolute path length in AD, which might indicate that the organization of the cortical network was the least optimal in AD. The small-world measures of the MCI network exhibited intermediate values. This finding is logical given that MCI is considered to be the transitional stage between normal aging and AD. Out of all the between-group differences in the clustering coefficient and absolute path length, only the differences between the AD and normal control groups were statistically significant. Compared with the normal controls, the MCI and AD groups retained their hub regions in the frontal lobe but showed a loss of hub regions in the temporal lobe. In addition, altered interregional correlations were detected in the parahippocampus gyrus, medial temporal lobe, cingulum, fusiform, medial frontal lobe, and orbital frontal gyrus in groups with MCI and AD. Similar to previous studies of functional connectivity, we also revealed increased interregional correlations within the local brain lobes and disrupted long distance interregional correlations in groups with MCI and AD.
Conflict of interest statement
The authors have declared that no competing interests exist.
Figures
Figure 1. The interregional correlations matrix in the AD, MCI and NC groups.
The color bar indicates the value of the correlation coefficient r (ranging from −0.8 to 1). A. The correlations matrices obtained by calculating the correlations between pairs of AAL areas within each group (left - the AD group, middle - the MCI group and right - the NC group). B. The binarized matrices obtained by thresholding the above correlations matrices of A with a sparsity threshold (15%). The sparsity threshold sets the same number of nodes and edges in each of the three cortical networks.
Figure 2. Small-world properties of the structural cortical networks.
The graphs show the absolute path lengths (Gamma γ = Cp real/Cp rand) and clustering coefficients (Lambda λ = Lp real/Lp rand) over a wide range of sparsity values (
) and the error bars were obtained using bootstrap method. All the networks have γ>1 (the blue lines) and λ≈1 (the black lines), which imply small-world properties. As the values of the sparsity thresholds increase, the γ values decrease rapidly and the λ values change only slightly. A – The values of Gamma and Lambda in NC. B – The values of Gamma and Lambda in MCI. C – The values of Gamma and Lambda in AD.
Figure 3. Mean clustering coefficients and mean absolute path lengths of the cortical networks in the three subject groups.
Mean clustering coefficient (Cp) and mean absolute path length (Lp) over a wide range of sparsity values (
) and the error bars were obtained using bootstrap method. A - The red stars represent the mean clustering coefficient in the AD group. The blue circles represent the mean clustering coefficient in the MCI group. The black squares represent the mean clustering coefficient in the NC group. B - The red stars represent the mean absolute path length in the AD group. The blue circles represent the mean absolute path length in the MCI group. The black squares represent the mean absolute path length in the NC group. The mean clustering coefficient was the greatest for the AD group and the absolute path length was shortest for the NC group. The measurements of the MCI group were intermediate between the NCs and ADs.
Figure 4. Between-group differences in the clustering coefficient (Cp) and the absolute path length (Lp) over a range of sparsity values.
The left shows the between-group differences in clustering coefficients (ΔCp) and the right shows the between-group differences in absolute path lengths (ΔLp) over a wide range of sparsity values (
). The black open circles represent the mean values and the black lines represent the 95% confidence intervals of the between-group differences obtained from 1000 permutation tests at each sparsity value. A - Differences between the NC and AD groups (ΔCp = CpNC−CpAD, ΔLp = LpNC−LpAD). B - Differences between the NC and MCI groups (ΔCp = CpNC−CpMCI, ΔLp = LpNC−LpMCI). C - Differences between the MCI and AD groups (ΔCp = CpMCI−CpAD, ΔLp = LpMCI−LpAD). The arrows indicate the significant (p<0.05) between-group differences in the clustering coefficients and absolute path lengths.
Figure 5. Abnormal changes in between-group nodal centrality in the MCI and AD groups.
Each of the eight regions belongs to the hub regions in at least one of the three cortical networks and showed a significant difference (p<0.05). The blue spheres indicate significant decreases in between-group nodal centrality. The red spheres indicate significant increases in between-group nodal centrality. A - Abnormal changes shared by the MCI and AD groups. B - Abnormal changes only in the AD group. Note that no abnormal changes occurred only in the MCI group. For the abbreviations of the regions, see Table 2.
Figure 6. Abnormal interregional correlations in the MCI and AD subjects.
The red and blue lines indicate significant between-group differences in interregional correlations between pairs of regions (p<0.01, FDR-corrected); the yellow dots represent those AAL regions with significantly abnormal correlations. The red and blue lines indicate the significantly increased and decreased interregional correlations between the corresponding regions, respectively. A - Significant changes in interregional correlations between the NC and AD groups. B - Significant changes in interregional correlations between the NC and MCI groups. C - Significant changes in interregional correlations between the MCI and AD groups. For the abbreviations of the regions, see Table 2.
References
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