Wavelet-based approaches for multiple hypothesis testing in activation mapping of functional magnetic resonance images of the human brain.

Wavelet-based methods for multiple hypothesis testing are described and their potential for activation mapping of human functional magnetic resonance imaging (fMRI) data is investigated. In this approach, we emphasize convergence between methods of wavelet thresholding or shrinkage and the problem of multiple hypothesis testing in both classical and Bayesian contexts. Specifically, our interest will be focused on ensuring a trade off between type I probability error control and power dissipation. We describe a technique for controlling the false discovery rate at an arbitrary level of type I error in testing multiple wavelet coefficients generated by a 2D discrete wavelet transform (DWT) of spatial maps of fMRI time series statistics. We also describe and apply recursive testing methods that can be used to define a threshold unique to each level and orientation of the 2D-DWT. Bayesian methods, incorporating a formal model for the anticipated sparseness of wavelet coefficients representing the signal or true image, are also tractable. These methods are comparatively evaluated by analysis of "null" images (acquired with the subject at rest), in which case the number of positive tests should be exactly as predicted under the hull hypothesis, and an experimental dataset acquired from 5 normal volunteers during an event-related finger movement task. We show that all three wavelet-based methods of multiple hypothesis testing have good type 1 error control (the FDR method being most conservative) and generate plausible brain activation maps.