Does parametric fMRI analysis with SPM yield valid results? An empirical study of 1484 rest datasets

The validity of parametric functional magnetic resonance imaging (fMRI) analysis has only been reported for simulated data. Recent advances in computer science and data sharing make it possible to analyze large amounts of real fMRI data. In this study, 1484 rest datasets have been analyzed in SPM8, to estimate true familywise error rates. For a familywise significance threshold of 5%, significant activity was found in 1%-70% of the 1484 rest datasets, depending on repetition time, paradigm and parameter settings. This means that parametric significance thresholds in SPM both can be conservative or very liberal. The main reason for the high familywise error rates seems to be that the global AR(1) auto correlation correction in SPM fails to model the spectra of the residuals, especially for short repetition times. The findings that are reported in this study cannot be generalized to parametric fMRI analysis in general, other software packages may give different results. By using the computational power of the graphics processing unit (GPU), the 1484 rest datasets were also analyzed with a random permutation test. Significant activity was then found in 1%-19% of the datasets. These findings speak to the need for a better model of temporal correlations in fMRI timeseries.