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Stability of graph theoretical measures in structural brain networks in Alzheimer's disease.

ABSTRACT: Graph analysis has become a popular approach to study structural brain networks in neurodegenerative disorders such as Alzheimer's disease (AD). However, reported results across similar studies are often not consistent. In this paper we investigated the stability of the graph analysis measures clustering, path length, global efficiency and transitivity in a cohort of AD (N?=?293) and control subjects (N?=?293). More specifically, we studied the effect that group size and composition, choice of neuroanatomical atlas, and choice of cortical measure (thickness or volume) have on binary and weighted network properties and relate them to the magnitude of the differences between groups of AD and control subjects. Our results showed that specific group composition heavily influenced the network properties, particularly for groups with less than 150 subjects. Weighted measures generally required fewer subjects to stabilize and all assessed measures showed robust significant differences, consistent across atlases and cortical measures. However, all these measures were driven by the average correlation strength, which implies a limitation of capturing more complex features in weighted networks. In binary graphs, significant differences were only found in the global efficiency and transitivity measures when using cortical thickness measures to define edges. The findings were consistent across the two atlases, but no differences were found when using cortical volumes. Our findings merits future investigations of weighted brain networks and suggest that cortical thickness measures should be preferred in future AD studies if using binary networks. Further, studying cortical networks in small cohorts should be complemented by analyzing smaller, subsampled groups to reduce the risk that findings are spurious.

SUBMITTER: Martensson G

PROVIDER: S-EPMC6072788 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Stability of graph theoretical measures in structural brain networks in Alzheimer's disease.

Mårtensson Gustav G Pereira Joana B JB Mecocci Patrizia P Vellas Bruno B Tsolaki Magda M Kłoszewska Iwona I Soininen Hilkka H Lovestone Simon S Simmons Andrew A Volpe Giovanni G Westman Eric E

Scientific reports 20180802 1

Graph analysis has become a popular approach to study structural brain networks in neurodegenerative disorders such as Alzheimer's disease (AD). However, reported results across similar studies are often not consistent. In this paper we investigated the stability of the graph analysis measures clustering, path length, global efficiency and transitivity in a cohort of AD (N = 293) and control subjects (N = 293). More specifically, we studied the effect that group size and composition, choice of n ...[more]

PMID: 30072774

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Project description:Alzheimer's disease (AD), an irreversible neurodegenerative disease, is the most common type of dementia in elderly people. This present study incorporated multiple structural and functional connectivity metrics into a graph theoretical analysis framework and investigated alterations in brain network topology in patients with mild cognitive impairment (MCI) and AD. By using this multiparametric analysis, we expected different connectivity metrics may reflect additional or complementary information regarding the topological changes in brain networks in MCI or AD. In our study, a total of 73 subjects participated in this study and underwent the magnetic resonance imaging scans. For the structural network, we compared commonly used connectivity metrics, including fractional anisotropy and normalized streamline count, with multiple diffusivity-based metrics. We compared Pearson correlation and covariance by investigating their sensitivities to functional network topology. Significant disruption of structural network topology in MCI and AD was found predominantly in regions within the limbic system, prefrontal and occipital regions, in addition to widespread alterations of local efficiency. At a global scale, our results showed that the disruption of the structural network was consistent across different edge definitions and global network metrics from the MCI to AD stages. Significant changes in connectivity and tract-specific diffusivity were also found in several limbic connections. Our findings suggest that tract-specific metrics (e.g., fractional anisotropy and diffusivity) provide more sensitive and interpretable measurements than does metrics based on streamline count. Besides, the use of inversed radial diffusivity provided additional information for understanding alterations in network topology caused by AD progression and its possible origins. Use of this proposed multiparametric network analysis framework may facilitate early MCI diagnosis and AD prevention.

Project description:BackgroundGraph theory has been recently introduced to characterize complex brain networks, making it highly suitable to investigate altered connectivity in neurologic disorders. A current model proposes autism spectrum disorder (ASD) as a developmental disconnection syndrome, supported by converging evidence in both non-syndromic and syndromic ASD. However, the effects of abnormal connectivity on network properties have not been well studied, particularly in syndromic ASD. To close this gap, brain functional networks of electroencephalographic (EEG) connectivity were studied through graph measures in patients with Tuberous Sclerosis Complex (TSC), a disorder with a high prevalence of ASD, as well as in patients with non-syndromic ASD.MethodsEEG data were collected from TSC patients with ASD (n = 14) and without ASD (n = 29), from patients with non-syndromic ASD (n = 16), and from controls (n = 46). First, EEG connectivity was characterized by the mean coherence, the ratio of inter- over intra-hemispheric coherence and the ratio of long- over short-range coherence. Next, graph measures of the functional networks were computed and a resilience analysis was conducted. To distinguish effects related to ASD from those related to TSC, a two-way analysis of covariance (ANCOVA) was applied, using age as a covariate.ResultsAnalysis of network properties revealed differences specific to TSC and ASD, and these differences were very consistent across subgroups. In TSC, both with and without a concurrent diagnosis of ASD, mean coherence, global efficiency, and clustering coefficient were decreased and the average path length was increased. These findings indicate an altered network topology. In ASD, both with and without a concurrent diagnosis of TSC, decreased long- over short-range coherence and markedly increased network resilience were found.ConclusionsThe altered network topology in TSC represents a functional correlate of structural abnormalities and may play a role in the pathogenesis of neurological deficits. The increased resilience in ASD may reflect an excessively degenerate network with local overconnection and decreased functional specialization. This joint study of TSC and ASD networks provides a unique window to common neurobiological mechanisms in autism.

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Stability of graph theoretical measures in structural brain networks in Alzheimer's disease.

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Stability of graph theoretical measures in structural brain networks in Alzheimer's disease.

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