Loss of ‘Small-World’ Networks in Alzheimer’s Disease: Graph Analysis of fMRI Resting-State Functional Connectivity

Ernesto J. Sanz-Arigita, Menno M. Schoonheim, Jessica S. Damoiseaux, Serge A. R. B. Rombouts, Erik Maris, Frederik Barkhof, Philip Scheltens, Cornelis J. Stam
PLoS ONE. 2010-11-01; 5(11): e13788
DOI: 10.1371/journal.pone.0013788

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1. PLoS One. 2010 Nov 1;5(11):e13788. doi: 10.1371/journal.pone.0013788.

Loss of ‘small-world’ networks in Alzheimer’s disease: graph analysis of FMRI
resting-state functional connectivity.

Sanz-Arigita EJ(1), Schoonheim MM, Damoiseaux JS, Rombouts SA, Maris E, Barkhof
F, Scheltens P, Stam CJ.

Author information:
(1)Department of Radiology, VU University Medical Center, Amsterdam, The

BACKGROUND: Local network connectivity disruptions in Alzheimer’s disease
patients have been found using graph analysis in BOLD fMRI. Other studies using
MEG and cortical thickness measures, however, show more global long distance
connectivity changes, both in functional and structural imaging data. The form
and role of functional connectivity changes thus remains ambiguous. The current
study shows more conclusive data on connectivity changes in early AD using graph
analysis on resting-state condition fMRI data.
METHODOLOGY/PRINCIPAL FINDINGS: 18 mild AD patients and 21 healthy age-matched
control subjects without memory complaints were investigated in resting-state
condition with MRI at 1.5 Tesla. Functional coupling between brain regions was
calculated on the basis of pair-wise synchronizations between regional
time-series. Local (cluster coefficient) and global (path length) network
measures were quantitatively defined. Compared to controls, the characteristic
path length of AD functional networks is closer to the theoretical values of
random networks, while no significant differences were found in cluster
coefficient. The whole-brain average synchronization does not differ between
Alzheimer and healthy control groups. Post-hoc analysis of the regional
synchronization reveals increased AD synchronization involving the frontal
cortices and generalized decreases located at the parietal and occipital regions.
This effectively translates in a global reduction of functional long-distance
links between frontal and caudal brain regions.
CONCLUSIONS/SIGNIFICANCE: We present evidence of AD-induced changes in global
brain functional connectivity specifically affecting long-distance connectivity.
This finding is highly relevant for it supports the anterior-posterior
disconnection theory and its role in AD. Our results can be interpreted as
reflecting the randomization of the brain functional networks in AD, further
suggesting a loss of global information integration in disease.

DOI: 10.1371/journal.pone.0013788
PMCID: PMC2967467
PMID: 21072180 [Indexed for MEDLINE]

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