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Cited by 215Functional Brain Connectivity StudiesDementia and Cognitive Impairment ResearchComplex Network Analysis Techniques

The DOI matches its Crossref record; 95 of the 95 references it cites were found in a registry or an index.

Disrupted Small-World Brain Networks in Moderate Alzheimer's Disease: A Resting-State fMRI Study

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Zhao, Xiaohu, Liu, Yong, Wang, Xiangbin, Liu, Bing, Xi, Qian, Guo, Qihao, Jiang, Hong, Jiang, Tianzi, Wang, Peijun·2012·PLoS ONE
DOI 10.1371/journal.pone.0033540PMC PMC3311642
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Abstract

The small-world organization has been hypothesized to reflect a balance between local processing and global integration in the human brain. Previous multimodal imaging studies have consistently demonstrated that the topological architecture of the brain network is disrupted in Alzheimer's disease (AD). However, these studies have reported inconsistent results regarding the topological properties of brain alterations in AD. One potential explanation for these inconsistent results lies with the diverse homogeneity and distinct progressive stages of the AD involved in these studies, which are thought to be critical factors that might affect the results. We investigated the topological properties of brain functional networks derived from resting functional magnetic resonance imaging (fMRI) of carefully selected moderate AD patients and normal controls (NCs). Our results showed that the topological properties were found to be disrupted in AD patients, which showing increased local efficiency but decreased global efficiency. We found that the altered brain regions are mainly located in the default mode network, the temporal lobe and certain subcortical regions that are closely associated with the neuropathological changes in AD. Of note, our exploratory study revealed that the ApoE genotype modulates brain network properties, especially in AD patients.

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Figure 1 Change of network parameters as a function of connection density (Cost). Clustering coefficient (A), shortest path length (B), global efficiency (C) and local efficiency (D) of the AD (green line) and NC (red line) groups as a function of Cost. Clustering coefficient (E), shortest path length (F), global efficiency (G) and local efficiency (H) of the AD ApoE4+ (black line), AD ApoE4− (blue line) and NC ApoE4− (red line) groups as a function of Cost. The error bars correspond to the standard error of the mean. Blue asterisks indicate where the difference between the NC and AD groups is significant (P<0.05). Blue circles indicate points where the difference between the AD ApoE4− group and the NC ApoE4− group is significant (P<0.05). Blue squares indicate points where the difference between the AD ApoE4+ group and the NC ApoE4− group is significant (P<0.05). The difference between the AD ApoE− group and the AD ApoE+ group is not significant at any Cost (P>0.05).
Figure 1 Change of network parameters as a function of connection density (Cost). Clustering coefficient (A), shortest path length (B), global efficiency (C) and local efficiency (D) of the AD (green line) and NC (red line) groups as a function of Cost. Clustering coefficient (E), shortest path length (F), global efficiency (G) and local efficiency (H) of the AD ApoE4+ (black line), AD ApoE4− (blue line) and NC ApoE4− (red line) groups as a function of Cost. The error bars correspond to the standard error of the mean. Blue asterisks indicate where the difference between the NC and AD groups is significant (P<0.05). Blue circles indicate points where the difference between the AD ApoE4− group and the NC ApoE4− group is significant (P<0.05). Blue squares indicate points where the difference between the AD ApoE4+ group and the NC ApoE4− group is significant (P<0.05). The difference between the AD ApoE− group and the AD ApoE+ group is not significant at any Cost (P>0.05).CC BY · PubMed Central
Figure 2 Change of small-world network definition parameters as a function of connection density (Cost).γ (A), λ (B), and σ (C) of the AD (green line) and NC (red line) groups as a function of Cost. γ (D), λ (E), and σ (F) of the AD ApoE4+ (black line), AD ApoE4− (blue line) and NC ApoE4− (red line) groups as a function of Cost. The error bars correspond to the standard error of the mean. Blue asterisks indicate points where the difference between the two groups is significant (P<0.05). Blue circles indicate points where the difference between the AD ApoE4− group and the NC ApoE4− groups is significant (P<0.05). No significant differences were found between the NC ApoE4− and AD ApoE4+ groups at any threshold (P>0.05) or between the ApoE4− and AD ApoE4+ groups.
Figure 2 Change of small-world network definition parameters as a function of connection density (Cost).γ (A), λ (B), and σ (C) of the AD (green line) and NC (red line) groups as a function of Cost. γ (D), λ (E), and σ (F) of the AD ApoE4+ (black line), AD ApoE4− (blue line) and NC ApoE4− (red line) groups as a function of Cost. The error bars correspond to the standard error of the mean. Blue asterisks indicate points where the difference between the two groups is significant (P<0.05). Blue circles indicate points where the difference between the AD ApoE4− group and the NC ApoE4− groups is significant (P<0.05). No significant differences were found between the NC ApoE4− and AD ApoE4+ groups at any threshold (P>0.05) or between the ApoE4− and AD ApoE4+ groups.CC BY · PubMed Central
Figure 3 Surface rendering of the distribution of altered nodes (P<0.05). Nodes with altered times greater than 10 across the 19 comparisons are shown. Colored bars indicate altered times. Regions showing significant alterations in Cp and Elocal are widely distributed across the brain, especially in the default mode network (such as the PCC_R, ACC, IFGoper, and SFG), regions in the temporal lobe (such as the STG) and regions in the subcortical structure (such as the THA_R, PAL_L and PUT_R). Significant alterations in Eglobal and Lp are primarily found in temporal lobe regions, such as the MTGp and MTG_R, and sensory motor regions, such as the SMA_R and PreCG_R.
Figure 3 Surface rendering of the distribution of altered nodes (P<0.05). Nodes with altered times greater than 10 across the 19 comparisons are shown. Colored bars indicate altered times. Regions showing significant alterations in Cp and Elocal are widely distributed across the brain, especially in the default mode network (such as the PCC_R, ACC, IFGoper, and SFG), regions in the temporal lobe (such as the STG) and regions in the subcortical structure (such as the THA_R, PAL_L and PUT_R). Significant alterations in Eglobal and Lp are primarily found in temporal lobe regions, such as the MTGp and MTG_R, and sensory motor regions, such as the SMA_R and PreCG_R.CC BY · PubMed Central
Figure 4 Surface rendering of the distribution of altered nodes at a connection density of 22%. Colored bars indicate differences in network properties between the NC and AD groups. Blue indicates regions showing an increase in the AD group but not the NCs. Yellow indicates regions showing a decrease in the AD group but not the NCs. In the AD group, the regions showing significant increases in Cp, Lp and Elocal are widely distributed across the brain, especially in default mode network regions such as the ACC, PCC, MPFC, HIP and IPL; regions in the temporal lobe such as the STGp/MTGp; and regions in the subcortical structure such as the THA, INS and PUT. The regions showing significant Eglobal decreases in AD are distributed primarily in the bilateral MTG and motor areas such as the SMA_R and PreCG_R.
Figure 4 Surface rendering of the distribution of altered nodes at a connection density of 22%. Colored bars indicate differences in network properties between the NC and AD groups. Blue indicates regions showing an increase in the AD group but not the NCs. Yellow indicates regions showing a decrease in the AD group but not the NCs. In the AD group, the regions showing significant increases in Cp, Lp and Elocal are widely distributed across the brain, especially in default mode network regions such as the ACC, PCC, MPFC, HIP and IPL; regions in the temporal lobe such as the STGp/MTGp; and regions in the subcortical structure such as the THA, INS and PUT. The regions showing significant Eglobal decreases in AD are distributed primarily in the bilateral MTG and motor areas such as the SMA_R and PreCG_R.CC BY · PubMed Central
Figure 5 Surface rendering of the distribution of nodes differing between the AD ApoE4+ and ApoE4− groups. Colored bars indicate differences in network properties between the two groups. Blue indicates regions showing an increase in the AD ApoE4+ group. Yellow indicates regions showing a decrease in the AD ApoE4+ group. The ApoE4− group displayed higher Cp, higher Elocal, and longer Lp in the temporal, frontal and medial prefrontal cortexes, and lower Eglobal in the frontal cortex.
Figure 5 Surface rendering of the distribution of nodes differing between the AD ApoE4+ and ApoE4− groups. Colored bars indicate differences in network properties between the two groups. Blue indicates regions showing an increase in the AD ApoE4+ group. Yellow indicates regions showing a decrease in the AD ApoE4+ group. The ApoE4− group displayed higher Cp, higher Elocal, and longer Lp in the temporal, frontal and medial prefrontal cortexes, and lower Eglobal in the frontal cortex.CC BY · PubMed Central

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Metadata

Authors
Zhao, X., Liu, Y., Wang, X., Liu, B., Xi, Q., Guo, Q., Jiang, H., Jiang, T., & Wang, P.
Affiliations
  • Tongji University (CN)
  • Chinese Academy of Sciences (CN)
  • Shanghai Medical College of Fudan University (CN)
  • University of Electronic Science and Technology of China (CN)
Corresponding author
  • Jiang, Tianzi
  • Wang, Peijun
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2012-03-23
Volume
7
Issue
3
Pages
e33540
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0033540
PMC
PMC3311642
OpenAlex
W2003131754
Cited by
215
References
95
Citations by year
2026: 6 · 2025: 5 · 2024: 9 · 2023: 9 · 2022: 9 · 2021: 24 · 2020: 16 · 2019: 17 · 2018: 24 · 2017: 21 · 2016: 21 · 2015: 19 · 2014: 16 · 2013: 16 · 2012: 3
FWCI
8.85
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • National Natural Science Foundation of China (30770615, 30970818, 863 Program, 60831004, 2011CBA00408, 30970770)
  • National High-tech Research and Development Program
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Physical Sciences › Physics and Astronomy › Statistical and Nonlinear Physics › Complex Network Analysis Techniques
Keywords
Alzheimer's disease, small-world networks, functional brain networks, network topology, local efficiency, global efficiency, default mode network, temporal lobe, subcortical structures, APOE genotype, resting-state fMRI
MeSH terms
Aged, Alzheimer Disease, Apolipoproteins E, Brain, Female, Genotype, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Case-Control Studies

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