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Dear Natalie,

We are addressing some reviewer concerns. My block design is ABACABAC. At
> the subject first-level, I modeled each of my three conditions (3 separate
> EVs), and specified two contrasts: B>A, and C>A with standard cluster
> thresholding z-score of 2.3 and significance level of p=.05. For contrast
> B>A (the EV for C was set at 0).  Likewise, for contrast C>A (the EV for B
> =0).
>
> At the higher-level, I used Flame 1+2, cluster Z>2.3, p<.05.
>
> The reviewer noted that two separate analyses were performed for B and C
> and said this doubles chances of finding a result by chance. I have been
> asked to either correct for repeat testing or incorporate both conditions
> into the model.
>
> How can I correct for repeat testing? I understand I can’t use p=0.025 for
> example as changing the p-value in this way would correspond to a
> voxel-wise uncorrected value and does not relate to the final cluster-level
> corrected p-value.
>

A Bonferroni correction can indeed be applied to (familywise) error
corrected P-values; you simply need to change the "p<.05" above to "p<.025".

I'm not exactly sure what the reviewer is getting at.  They *might* be
wondering if a common effect in B>A and C>A is due to a *decrease* in A; if
you have any rest scans in your design you can try to look at the pure
effect of A<0 to check this.  Or, they might be after the usual
multiplicity issue, that any time you look at multiple tests you increase
your risk of false positives.

I should say this second concern is a fairly knotty issue.  What if you had
only reported on B>A and then passed your data on to a friend who published
C>A?  Should you have corrected for the inference across the two papers?
 There's no hard and fast rule, but one line of reasoning goes like this:
If you needed to look at all of a set of contrasts to answer a scientific
question, then you should be correcting for multiplicity.  If each contrast
answers a distinct question that you interpret in isolation (and could,
conceivably, be written up on it's own as a scientific work), *and* there
aren't *too* many of them in total, then you can get away with out
correction.

There's no hard rule on this, and I won't try to define "too many", but
here's an example of the former:  Say you fit an FIR HRF, where you have,
say, 10 EV's that model the HRF response at each of 10 lags.  I don't think
any reasonable person would say each of the 10 COPEs are answering a
distinct question, and you'd have to deal with the multiplicity over the 10
tests.

Hope this helps!

-Tom




-- 
__________________________________________________________
Thomas Nichols, PhD
Principal Research Fellow, Head of Neuroimaging Statistics
Department of Statistics & Warwick Manufacturing Group
University of Warwick, Coventry  CV4 7AL, United Kingdom

Web: http://go.warwick.ac.uk/tenichols
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