Abstract
Functional brain networks detected in task-free (“resting-state”) functional magnetic resonance imaging (fMRI) have a small-world architecture that reflects a robust functional organization of the brain. Here, we examined whether this functional organization is disrupted in Alzheimer's disease (AD). Task-free fMRI data from 21 AD subjects and 18 age-matched controls were obtained. Wavelet analysis was applied to the fMRI data to compute frequency-dependent correlation matrices. Correlation matrices were thresholded to create 90-node undirected-graphs of functional brain networks. Small-world metrics (characteristic path length and clustering coefficient) were computed using graph analytical methods. In the low frequency interval 0.01 to 0.05 Hz, functional brain networks in controls showed small-world organization of brain activity, characterized by a high clustering coefficient and a low characteristic path length. In contrast, functional brain networks in AD showed loss of small-world properties, characterized by a significantly lower clustering coefficient (p<0.01), indicative of disrupted local connectivity. Clustering coefficients for the left and right hippocampus were significantly lower (p<0.01) in the AD group compared to the control group. Furthermore, the clustering coefficient distinguished AD participants from the controls with a sensitivity of 72% and specificity of 78%. Our study provides new evidence that there is disrupted organization of functional brain networks in AD. Small-world metrics can characterize the functional organization of the brain in AD, and our findings further suggest that these network measures may be useful as an imaging-based biomarker to distinguish AD from healthy aging.
Highlights
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive impairment of episodic memory and other cognitive domains resulting in dementia and, death
Using functional magnetic resonance imaging (fMRI), we demonstrated that AD patients performing a simple motor task had reduced intra-subject functional connectivity within a network of brain regions—termed the default-mode network—that includes posterior cingulate cortex, temporoparietal junction, and hippocampus [10]
Alzheimer’s disease (AD) is a brain disorder characterized by progressive impairment of episodic memory and other cognitive domains resulting in dementia and, death
Summary
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive impairment of episodic memory and other cognitive domains resulting in dementia and, death. FMRI studies have moved beyond focal activation abnormalities to dysfunctional brain connectivity. PET studies, restricted to across-subject connectivity measures, have shown that AD patients have decreased hippocampus connectivity with prefrontal cortex [8] and posterior cingulate cortex [9] during memory tasks. Using fMRI, we demonstrated that AD patients performing a simple motor task had reduced intra-subject functional connectivity within a network of brain regions—termed the default-mode network—that includes posterior cingulate cortex, temporoparietal junction, and hippocampus [10]. Three recent studies have reported reduced default-mode network deactivation in MCI and/ or AD patients during encoding tasks [12,13] and during a semantic classification task [14]. Celone et al reported increased default-mode network deactivation in a subset of ‘‘less impaired’’ MCI patients
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