Investigating the impact of autocorrelation on time-varying connectivity

In recent years, a number of studies have reported on the existence of time-varying functional connectivity (TVC) in resting-state functional magnetic resonance imaging (rs-fMRI) data. The sliding-window technique is currently one of the most commonly used methods to estimate TVC. Although previous studies have shown that autocorrelation can negatively impact estimates of static functional connectivity, its impact on TVC estimates is not well known at this time. In this paper, we show both theoretically and empirically that the existence of autocorrelation within a time series can inflate the sampling variability of TVC estimated using the sliding-window technique. This can in turn increase the risk of misinterpreting noise as true TVC and negatively impact subsequent estimation of whole-brain time-varying FC profiles, or "brain states". The latter holds as more variable input measures lead to more variable output measures in the state estimation procedure. Finally, we demonstrate that prewhitening the data prior to analysis can lower the variance of the estimated TVC and improve brain state estimation. These results suggest that careful consideration is required when making inferences on TVC.