Proportional thresholding in resting‐state fMRI functional connectivity networks and consequences for patient‐control connectome studies: Issues and recommendations

By Martijn P. van den Heuvel, S. D. de Lange, Andrew Zalesky, Caio Seguin, Thomas Yeo, Ruben Schmidt. NeuroImage, 2017

455 citations recorded by the source corpus.

ABSTRACT Graph theoretical analysis has become an important tool in the examination of brain dysconnectivity in neurological and psychiatric brain disorders. A common analysis step in the construction of the functional graph or network involves “thresholding” of the connectivity matrix, selecting the set of edges that together form the graph on which network organization is evaluated. To avoid systematic differences in absolute number of edges, studies have argued against the use of an “absolute threshold” in case‐control studies and have proposed the use of “proportional thresholding” instead, in which a pre‐defined number of strongest connections are selected as network edges, ensuring equal network density across datasets. Here, we systematically studied the effect of proportional thresholding on the construction of functional matrices and subsequent graph analysis in patient‐control functional connectome studies. In a few simple experiments we show that differences in overall strength of functional connectivity (FC) – as often observed between patients and controls – can have predictable consequences for between‐group differences in network organization. In individual networks with lower overall FC the proportional thresholding algorithm has to select more edges based on lower correlations, which have (on average) a higher probability of being spurious, and thus introduces a higher degree of randomness in the resulting network. We show across both empirical and artificial patient‐control datasets that lower levels of overall FC in either the patient or control group will most often lead to differences in network efficiency and clustering, suggesting that differences in FC across subjects will be artificially inflated or translated into differences in network organization. Based on the presented case‐control findings we inform about the caveats of proportional thresholding in patient‐control studies in which groups show a between‐group difference in overall FC. We make recommendations on how to examine, report and to take into account overall FC effects in future patient‐control functional connectome studies. HighlightsProportional thresholding is a commonly used analysis step in the reconstruction of functional brain networks to ensure equal density across patient and control samples.Proportional thresholding may result in the inclusion of more spurious connections in datasets based on low overall functional connectivity (FC).When graph analysis is applied to these networks low overall FC may translate into more random network characterization.Systematic differences in overall FC between patients and controls can artificially inflate differences in network organization.We recommend to test and control for differences in overall FC in functional disease connectome studies.

Subfields: Cognitive Neuroscience, Experimental and Cognitive Psychology

View Paper: https://www.semanticscholar.org/paper/f76de26cc9e89c122f8a83f1cda437797486476d

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Citations in the corpus

Application of Graph Theory for Identifying Connectivity Patterns in Human Brain Networks: A Systematic Review (2019, background): “The contribution of rs-fMRI studies based on graph theory for autism exploration is considerable (Redcay et al., 2013; Rudie et al., 2013; Di Martino et al., 2014; Keown et al., 2017; van den Heuvel et al., 2017; Kazeminejad and Sotero, 2018).”
Resting-state EEG connectome topology and social norm processing in healthy young adults (2026, unknown): “…for each of which the graph-theoretical metrics of interest are extracted, and calculates the area under the curve (AUC), thereby defining an aver - age value as a threshold-independent measure for each selected metric (Ginestet et al. 2011; Hosseini et al. 2012; Van Den Heuvel et al. 2017 ).”
Task‐specific topology of brain networks supporting working memory and inhibition (2024, methodology): “Adjacency matrices were transformed into networks through quartile thresholding (Adamovich et al., 2022; van den Heuvel et al., 2017).”