Functional connectivity change as shared signal dynamics

Background: An increasing number of neuroscientific studies gain insights by focusing on differences in functional connectivity between groups, individuals, temporal windows, or task conditions. We found using simulations that additional insights into such differences can be gained by forgoing variance normalization, a procedure used by most functional connectivity measures. Simulations indicated that these functional connectivity measures are sensitive to increases in independent fluctuations (unshared signal) in time series, consistently reducing functional connectivity estimates (e.g., correlations) even though such changes are unrelated to corresponding fluctuations (shared signal) between those time series. This is inconsistent with the common notion of functional connectivity as the amount of inter-region interaction. New method: Simulations revealed that a version of correlation without variance normalization - covariance - was able to isolate differences in shared signal, increasing interpretability of observed functional connectivity change. Simulations also revealed cases problematic for non-normalized methods, leading to a "covariance conjunction" method combining the benefits of both normalized and non-normalized approaches. Results: We found that covariance and covariance conjunction methods can detect functional connectivity changes across a variety of tasks and rest in both clinical and non-clinical functional MRI datasets. Comparison with existing method(s): We verified using a variety of tasks and rest in both clinical and non clinical functional MRI datasets that it matters in practice whether correlation, covariance, or covariance conjunction methods are used. Conclusions: These results demonstrate the practical and theoretical utility of isolating changes in shared signal, improving the ability to interpret observed functional connectivity change. (C) 2015 Elsevier B.V. All rights reserved.