Simple explanations before complex theories: Alternative interpretations of Sirotin and Das' observations

We make a few additional points regarding our discussion with Sirotin and Das' 2009 Nature paper and their 2011 NeuroImage response to our commentary. While we find their data interesting in itself, we remain concerned with how the data are interpreted by the authors. We discuss two categories of methodological issues that limit the conclusions one can draw from their results. (1) The measures of fit quality between the optical and electrical data: kernel shape variation, variance of predicted/measured signals, and R2, interact with each other and are confounded by the fact that one condition has a lower signal magnitude and therefore, lower signal-to-noise-ratio (SNR). (2) Hemodynamic responses to distinct events will be incorrectly or inefficiently estimated if the hemodynamic responses overlap across periodic trials that are not jittered and have an inter-trial interval less than 15 s. Most importantly, the overlapping responses across trials might cause transient effects that look similar to the anticipatory effects presented by Sirotin and Das. While their study demonstrates a potentially useful way to probe neurovascular coupling, we believe the current results have little practical relevance for interpreting hemodynamic measures of neural activity such as those used in fMRI. We conclude by making several suggestions for future analyses, which might help elucidate the mechanisms behind these observations and lead to a better understanding of how these observations relate to hemodynamic based measures of neural activation.