Exploring resting-state functional connectivity with total interdependence.

Resting-state fMRI has become a powerful tool for studying network mechanisms of normal brain functioning and its impairments by neurological and psychiatric disorders. Analytically, independent component analysis and seed-based cross correlation are the main methods for assessing the connectivity of resting-state fMRI time series. A feature common to both methods is that they exploit the covariation structures of contemporaneously (zero-lag) measured data but ignore temporal relations that extend beyond the zero-lag. To examine whether data covariations across different lags can contribute to our understanding of functional brain networks, a measure that can uncover the overall temporal relationship between two resting-state BOLD signals is needed. In this paper we propose such a measure referred as total interdependence (TI). Comparing TI with zero-lag cross correlation (CC) we report three results. First, when combined with a random permutation procedure, TI can reveal the amount of temporal relationship between two resting-state BOLD time series that is not captured by CC. Second, comparing resting-state data with task-state data recorded in the same scanning session, we demonstrate that the resting-state functional networks constructed with TI match more precisely the networks activated by the task. Third, TI is shown to be more statistically sensitive than CC and provides better feature vectors for network clustering analysis.