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Functional magnetic resonance imaging (fMRI)-based functional connectivity (FC) commonly characterizes the functional connections in the brain. Conventional quantification of FC by Pearson's correlation captures linear, time-domain dependencies among blood-oxygen-level-dependent (BOLD) signals. We examined measures to quantify FC by investigating: (i) Is Pearson's correlation sufficient to characterize FC? (ii) Can alternative measures better quantify FC? (iii) What are the implications of using alternative FC measures? FMRI analysis in healthy adult population suggested that: (i) Pearson's correlation cannot comprehensively capture BOLD inter-dependencies. (ii) Eight alternative FC measures were similarly consistent between task and resting-state fMRI, improved age-based classification and provided better association with behavioral outcomes. (iii) Formulated hypotheses were: first, in lieu of Pearson’s correlation, an augmented, composite and multi-metric definition of FC is more appropriate; second, canonical large-scale brain networks may depend on the chosen FC measure. A thorough notion of FC promises better understanding of variations within a given population.

Rethinking Measures of Functional Connectivity via Feature Extraction