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I'm actually with Roberto on this one. In all these cases, we're using
inferential statistics. The validity of the *inference* that we make
based upon the statistics is the important thing in this case. If we
clearly state that the inference is limited by the apriori
assumption/condition that we made, then we shouldn't have a problem.

Take the trivial case of a functionally defined mask based on a
contrast A that is used to mask the same contrast, as mentioned by
Stephen. Obviously the inference "in this region of the brain, A was
significant" would be non-valid. But if instead we made the inference
"in regions of the brain where A was significant we were able to show
that A was significant" we would be absolutely fine, statistically and
inferentially speaking, though a reviewer would question our sanity in
finding it worthwhile to report.

A more realistic example: I perform a study in which I show people
angry and happy faces and black dots. I define a contrast face-dot and
find regions of the brain showing this effect. I use those regions as
a functionally-defined ROI and test the angry-happy contrast. What
inferences can I make? "In regions showing greater activation for
angry and happy faces than for dots, we found angry faces to produce
greater activation than happy faces". This would be fine I think. But
it would be wrong to drop the first part of that statement.

-Tom

On Thu, Oct 2, 2008 at 1:56 PM, Fromm, Stephen (NIH/NIMH) [C]
<[log in to unmask]> wrote:
> Roberto,
>
> Sorry if this isn't addressing your points; the original poster's
> question was a little unclear to me, because I wasn't 100% sure what she
> meant by "multi-masking."
>
> All I mean is that if you use a mask defined by the same functional data
> that you're applying the mask to, the significance will possibly be
> inflated.
>
> As for definitions, an example which is somewhat conceptually related is
> stepwise regression.  The paper at
>    http://publish.uwo.ca/~harshman/ssc2006a.pdf
> states, "When model modifications are selected using post-hoc
> information (e.g., in stepwise regression) standard estimates of
> p-values become biased."  Ultimately, I think my use of "bias" here is
> correct, based on definitions given at Wikipedia.
>
> So, what I'm saying here is that the use of a functionally defined mask
> can lead to corrected p-values which are likely to be too small.  The
> simplest example is using a contrast to mask itself.  The uncorrected
> p-values are obviously unaffected by this procedure.  And the corrected
> p-values are obviously decreased.
>
> My comment "the mathematics dictates that there is no bias":  I mean
> that I assume that there are situations where there's enough
> independence (e.g, perhaps between the masking contrast and the contrast
> you're masking) that the bias either doesn't exist or is probably
> negligible, but I haven't had time to think up rigorous examples.
>
> Best regards,
>
> S
>
> -----Original Message-----
> From: [log in to unmask] [mailto:[log in to unmask]]
> Sent: Thursday, October 02, 2008 8:16 AM
> To: Fromm, Stephen (NIH/NIMH) [C]
> Cc: [log in to unmask]
> Subject: Re: Multi-masking for Multiple Comparison Correction
>
> Could you be more specific? I can't see what you mean by "the
> mathematics dictates that there is no bias". It's important to avoid
> misunderstandings about the terminology: bias is a technical term,
> defined on the power function of the test, and does not mean just
> wrong in some way. You should be sure that when you mention bias you
> do not mean "conditional on the functional data", as I mentioned in my
> mail.
>
> R.V.
>
> <snip>
>> Except in certain circumstances, where you could show that the
> mathematics
>> dictates that there's no bias, defining regions based on the
> functional data
>> itself can definitely bias results, regardless of whether the
>> contrast is defined
>> a priori.
>>
>> Perhaps one can argue that the bias is slight; and it's certainly
> common
>> practice in the neuroimaging community.  But, again, procedures that
> look to
>> the data can lead to bias.
>>
>> Of course, if one uses separately acquired data to create the
> contrast-
>> defined ROI, that's a different matter.
>>
>>> In some specific instance, using the mask approach follows a clear
>>> substantive logic. For example, if you are investigating individual
>>> differences in cognitive capacity, you may be justified in carrying
>>> out a contrast first, and then look at how individual differences
>>> modulate the activation say, in prefrontal and parietal areas.
>>>
>>> You do have to pay for the increased power (if the procedure is
> really
>>> a priori), the price being that you potentially miss an effect in the
>>> voxels outside the mask.
>>>
>>> I do not see any simple way in which the concept of bias relates to
>>> this specific situation; I'd rather say that these tests are
>>> conditional on the a priori criterion. If the criterion is not a
>>> priori, they have wrong significance values (too small), with
> inflated
>>> type I errors.
>>>
>>> When you use a cluster approach, you also have to specify a priori a
>>> cluster definition threshold. Your p values are conditional on this
>>> threshold. If you try several thresholds, your test will have wrong p
>>> values.
>>>
>>> All the best,
>>> Roberto Viviani
>>> University of Ulm, Germany
>>>
>>> Quoting Amy Clements <[log in to unmask]>:
>>>
>>>> Dear Experts,
>>>>
>>>> I am pretty far away from having statistical expertise, which is why
>>>>  I am posing my question to the group.  Recently, I have seen a
>>>> multitude of papers that are using a multi-masking approach to deal
>>>> with corrections for multiple comparisons (using main effect or
>>>> other effects of interest contrasts masks).  While on the surface
>>>> this appears to seem like an optimal approach because you are
>>>> restricting the number of voxels included in the multiple
>>>> comparison, it seems like an opportunity for biasing the data and
>>>> obtained results--especially if you are not masking the data based
>>>> from a priori hypotheses (e.g., using a previously defined
>>>> functional ROI mask because you're interested in face processing).
>>>>
>>>> I'm not sure that I've articulated this is the best way.  It seems,
>>>> like I mentioned previously, to have the potential to bias results,
>>>> but would greatly appreciate feedback.  The questions typically
>>>> asked from the lab that I've worked in have been better suited to
>>>> utilizing a cluster-based approach; however, could also be served by
>>>>  multi-masking.
>>>>
>>>> Thanks!
>>>>
>>>>
>>>> Amy Stephens
>>>>
>>>>
>>>>
>>>>
>>>>
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>>
>>
>>
>



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