Dear all,

The B&H procedure is dependent on the number of tests and, for 
neuroimaging methods, more tests is often equivalent to higher 
resolution, either in voxel-based or surface-based representations of 
the brain. The question that arises is whether this would influence 
sensitivity and/or power. As long as changes in resolution are uniform 
in space (i.e. uniform lattice for voxel-based methods or homogeneous 
density of vertices for surface-based methods), then the resolution, by 
itself, should not interfere in the sensitivity or power. The 
proportions of errors type I and II should remain the same. There are 
just more points to look at. Note that the maximum p-value to obtain at 
least one rejection might change, but 1 may be 1% of 100 tests or 0.001% 
of 100000 tests, so the absolute number of rejections would not be a 
valid way to control the proportion of false discoveries.

However, this is not the end of the story. The noise and the size of the 
effect (in terms of area/volume) influence the p-values, hence the 
resulting threshold. In other words: while the *uniformity* of the 
resampling is important to ensure that the threshold would remain the 
same in terms of p-values, the noise and size of the "activation" also 
influence. Changes in resolution have the same overall effect of 
filtering in space. Gaussian filters, for instance, are known for 
highlighting signal areas which size matches the width of the filter, 
while burying into noise spatially small regions of signal. Reductions 
in resolution have an effect similar to average (mean) filtering for 
voxel-based methods, and to whatever equivalent for convolution would be 
defined for surface-based methods.

Therefore, I would conclude that it is not an FDR issue, but instead 
related to the ability to discriminate signal from noise in neighbouring 
voxels/vertices in different resolutions. While mean filtering 
(equivalent to lowering the resolution) may cancel out noise, increasing 
the value of the statistic, it may also dilute a small effect, causing 
the opposite result. For methods where the intensity of the voxel/vertex 
is the variable of interest, the "best" resolution should be no higher 
than what can be afforded by the device (unless taken into account 
somehow). For voxel-based methods (say, fMRI, PET), this is easy to 
achieve. For surface-based fMRI, for instance, it is certainly more 
complex and related to how the information from a certain voxel from MRI 
can be split or projected into more than one vertex. For surface-based 
cortical thickness, there might not be a "best" resolution, but to what 
concerns FDR and other multiple testing procedures, a roughly 
homogeneous density of vertices on space might be a desirable feature.

With respect to binning, although subsampling the vertices uniformly in 
space or selecting them after sorting should produce different 
thresholds, if the distribution of p-values is well behaved (i.e. no 
discrete distribution, uniform under null, etc) and if the bins are not 
too wide, then this difference should be negligible for practical purposes.

Hope this helps!

Anderson


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