000851051 001__ 851051 000851051 005__ 20240313095012.0 000851051 0247_ $$2doi$$a10.3389/fnins.2018.00528 000851051 0247_ $$2Handle$$a2128/19758 000851051 0247_ $$2pmid$$apmid:30323734 000851051 0247_ $$2WOS$$aWOS:000445926200001 000851051 0247_ $$2altmetric$$aaltmetric:45061175 000851051 037__ $$aFZJ-2018-04764 000851051 082__ $$a610 000851051 1001_ $$0P:(DE-Juel1)156326$$aBachmann, Claudia$$b0$$eCorresponding author 000851051 245__ $$aOn the Extraction and Analysis of Graphs From Resting-State fMRI to Support a Correct and Robust Diagnostic Tool for Alzheimer's Disease 000851051 260__ $$aLausanne$$bFrontiers Research Foundation$$c2018 000851051 3367_ $$2DRIVER$$aarticle 000851051 3367_ $$2DataCite$$aOutput Types/Journal article 000851051 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1568968807_23433 000851051 3367_ $$2BibTeX$$aARTICLE 000851051 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000851051 3367_ $$00$$2EndNote$$aJournal Article 000851051 520__ $$aThe diagnosis of Alzheimer's disease (AD), especially in the early stage, is still not very reliable and the development of new diagnosis tools is desirable. A diagnosis based on functional magnetic resonance imaging (fMRI) is a suitable candidate, since fMRI is non-invasive, readily available, and indirectly measures synaptic dysfunction, which can be observed even at the earliest stages of AD. However, the results of previous attempts to analyze graph properties of resting state fMRI data are contradictory, presumably caused by methodological differences in graph construction. This comprises two steps: clustering the voxels of the functional image to define the nodes of the graph, and calculating the graph's edge weights based on a functional connectivity measure of the average cluster activities. A variety of methods are available for each step, but the robustness of results to method choice, and the suitability of the methods to support a diagnostic tool, are largely unknown. To address this issue, we employ a range of commonly and rarely used clustering and edge definition methods and analyze their graph theoretic measures (graph weight, shortest path length, clustering coefficient, and weighted degree distribution and modularity) on a small data set of 26 healthy controls, 16 subjects with mild cognitive impairment (MCI) and 14 with Alzheimer's disease. We examine the results with respect to statistical significance of the mean difference in graph properties, the sensitivity of the results to model and parameter choices, and relative diagnostic power based on both a statistical model and support vector machines. We find that different combinations of graph construction techniques yield contradicting, but statistically significant, relations of graph properties between health conditions, explaining the discrepancy across previous studies, but casting doubt on such analyses as a method to gain insight into disease effects. The production of significant differences in mean graph properties turns out not to be a good predictor of future diagnostic capacity. 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