Subject: Re: Some Problems with Neuroimaging From: Michael Palij <[email protected]> Date: Thu, 12 Jul 2012 08:54:06 -0400 X-Message-Number: 2 On Wed, 11 Jul 2012 23:09:57 -0700, Mike Wiliams wrote:

However, the distribution of false positives across the voxel locations should be random.
Depends upon how defines "random".  Consider:
(1) For all t-tests, is N1=N2?  I know that you say you're
using paired t-tests but what guarantee is there that there
is always a matching value? How is such missing data
treated?
There is no missing data. The whole brain scans are replicated for active and rest phases of the study. There is a measurement taken of signal strength for every voxel for every whole-brain scan. I am conducting a paired t-test for a single voxel and subtracting the mean for the active condition from the mean for the rest condition. The number of measurements (N) is the same for each condition.
(2)  How are violations of the assumptions of paired t-tests handled?
Variance away from the mean values are stochastic error and there is no skew. If the distribution was abnormal and variances unequal then there would be something wrong with the scanner. This would
be obvious in the artifacts produced in the scans.

|The fact that the Salmon's randomly significant voxels clustered
|in the Salmon's brain cavity I consider extremely unlikely. What
|are the odds of this pattern occurring by chance?

Oh, so we're turning Bayesian now? ;-)  Let's start by asking
what is the baserate?

|There was likely some artifact that produced this, like they
|moved the Salmon's head slightly at the end of every activation run,
|or there was an intentional manipulation of the data.

Uh, yeah.

|From a random distribution of 1,000 t-tests, how many times to t-tests
|numbered 98,99 and 100 come up significant and all the others come
|up nonsignificant?

I don't understand your sentence above.  If you're asking what is the
overall Type I error rate for 1000 t-tests, this is given by the formula:

alpha-overall = (1 - (1- alpha-per comparison)**1000
Your formula specifies the probability of any voxel coming up significant by chance. Suppose you specify an alpha of .05. 5% of the voxels should be significant by chance.
However,  the significant t scores should be randomly distributed
across the voxels and all areas of the image. What are the odds of chance activations only in the voxels making up the Salmon's brain cavity? What are the odds of just voxels 4,5,&6 (the brain cavity) coming up significant and all the others coming up nonsignificant? The odds must be astronomical. Why were there no chance activations in other areas of the Salmon image? The odds of this occurring are so
small that some kind of manipulation was conducted to produce this extremely
rare pattern.



But, if I am reading the literature correctly, the Pearson r and sample size
and not routinely reported.  Nor are the power levels associated with each
test -- reducing alpha-per comparison will reduce the statistical power for
each test, thus increasing the Type II errors. So, do the corrections trade
Type I errors for Type II errors?

In other words, what are you talking about Willis?


The sample sizes are reported when the model is described. The number of whole brain scans for each condition in a block design is the sample size. I typically have 15 measurements for each condition for each voxel. The effect size for the BOLD response is more-or-less standardized. I just don't remember what it is. The % change in signal strength associated with the BOLD response was established very early and it has a classic pattern of onset, peak and diminishment that is well known and modeled in the
analyses.

Corrections are the default for the analysis software, such as SPM. You have to actively uncorrect the analysis if you want to see it uncorrected. It is also typical to reduce the voxel extent for clusters. Randomly distributed significant voxels don't usually cluster. By specifying a minimum cluster of
5 voxels, I can usually eliminate most of the random results.

The hypotheses of neuroimaging are not at the single t-test, voxel level. The hypothesis is typically that a cluster of voxels, a region of interest, demonstrates a BOLD response under the active condition. When I administer a Naming Test, I expect a typical pattern of voxel clusters representing the language areas of the left hemisphere. This usually happens. The problems with fMRI are the same problems that hamper any research design: researchers with weak theories and hypotheses about brain function are
essentially on a fishing expedition for fame and glory and not science.

Mike Williams

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