Tests for a difference in timing of physiological response between two brain regions measured by using functional magnetic resonance imaging

Summary.  Functional magnetic resonance imaging (FMRI) measures the physiological response of the human brain to experimentally controlled stimulation. In a periodically designed experiment it is of interest to test for a difference in the timing (phase shift) of the response between two anatomically distinct brain regions. We suggest two tests for an interregional difference in phase shift: one based on asymptotic theory and one based on bootstrapping. Whilst the two procedures differ in some of their assumptions, both tests rely on employing the large number of voxels (three-dimensional pixels) in non-activated brain regions to take account of spatial autocorrelation between voxelwise phase shift observations within the activated regions of interest. As an example we apply both tests, and their counterparts assuming spatial independence, to FMRI phase shift data that were acquired from a normal young woman during performance of a periodically designed covert verbal fluency task. We conclude that it is necessary to take account of spatial autocovariance between voxelwise FMRI time series parameter estimates such as the phase shift, and that the most promising way of achieving this is by modelling the spatial autocorrelation structure from a suitably defined base region of the image slice.