Re: [Freesurfer] GLM design question

Hi Martijn, yes, that is a good thing to do! doug

Martijn Steenwijk wrote:

Hi Doug,

Thanks for your reply again. It's getting more and more clear now.

I've however one question remaining, which is regarding the correction for sex. What I did not tell (my fault ;-) ), is that 75% of the cohort is female. Comparing the sex-corrected results with male-only and female-only results, it appears to me that the relatively small male-group partly 'drives' the results in the sex-corrected results. I guess this is because the males and females are currently equally weighted in the contrast matrices. Shouldn't the differences in sex also be represented in the contrast matrices, like [.25 .75 -.25 -.75 0 0 0 0 0 0 0 0] [0 0 .25 .75 -.25 -.75 0 0 0 0 0 0] [ .25 .75 0 0 -.25 -.75 0 0 0 0 0 0]

? Or am I wrong?

Best, Martijn

On Wed, Dec 21, 2011 at 5:45 PM, Douglas N Greve <greve@nmr.mgh.harvard.edu mailto:greve@nmr.mgh.harvard.edu> wrote:

Hi Martijn, sorry for  the delay. Your contrast matrices look
correct. The differences between demeaning and not demeaning is
somewhat expected. When you do not demean, you are testing whether
there is a difference between groups at age=0 (ie, birth). When
you demean, you are testing for a difference at age=MeanAge. If
the slope of each group with respect to age is the same, then this
will yield the same result since the regression lines will be
parallel and the distance between parallel lines will always be
the same. If the slopes differ, then the distance will change with
age. For example, there will be an age where the lines cross. If
you test at this age, you are assured not to see a difference! For
this reason, it is better to test for a difference in the slopes,
and, if there is no difference, then reanalyze with DOSS which
forces the lines to be parallel. In your case, you found that
there is some difference in insula. If this is not the area that
you are interested in, then I would not worry about it. You should
just keep in mind that you should not try to draw conclusions from
this area.
doug

Martijn Steenwijk wrote:

    Dear Doug,

    Thanks again for your reply. Based on that I did some further
    work.

    I first demeaned the age of all subjects. Actually, I have a
    third group which I would like to compare to, so my contrast
    matrices will be [.5 .5 -.5 -.5 0 0 0 0 0 0 0 0]
    [0 0 .5 .5 -.5 -.5 0 0 0 0 0 0]
    [.5 .5 0 0 -.5 -.5 0 0 0 0 0 0]
    to test for CT differences between all the groups while
    correcting for age and sex. Surprisingly, I'm observing a big
    difference in the results compared to the results without
    demeaning. Could you explain the reson for this? In the
    FSGD-examples (eg
    http://surfer.nmr.mgh.harvard.edu/fswiki/FsgdFormat), age is
    also not normalized. Does normalizing the variance to 1 also
    influence the results?
    Given this big difference, I started wondering whether it
    would maybe be better to analyze the data in pairs of two
    groups (and then demean by the mean of the two groups). Would
    this be a better approach?

    Concerning your second suggestion: if I test the data for
    differences in group slope, a number of small area's are
    significantly different. Regions popping up are especially in
    the neighborhood of the insula. Unfortunately this suggests
    that I cannot use the DOSS model, or am I wrong?

    Looking forward to your reply,
    With best regards,
    Martijn


    On Sat, Dec 10, 2011 at 7:16 PM, Douglas Greve
    <greve@nmr.mgh.harvard.edu <mailto:greve@nmr.mgh.harvard.edu>
    <mailto:greve@nmr.mgh.harvard.edu
    <mailto:greve@nmr.mgh.harvard.edu>>> wrote:

       Yes, that is correct, though I think your matrix should be
    [.5 .5
       -.5 -.5 0 0 0 0]. You should also remove the mean from the age
       (mean computed from all subjects). Or even better, first test
       whether there is a group difference in age slope with [0 0
    0 0 .5
       .5 -.5 -.5]. If there is nothing that is significant, then
    re-run
       your analysis using the Different Offset Same Slope (DOSS)
    model
       with this contrast [.5 .5 -.5 -.5 0].

       doug


       On 12/10/11 4:15 AM, Martijn Steenwijk wrote:


           Dear all,


           I’m relatively new with Freesurfer, but slowly getting
        more and
           more used to it’s great possibilities. To be ‘sure’, I’ve a
           question about the design of a GLM.


           I want to compare CT in Healthy Controls vs Diseased,
        and control
           for age and sex. It appears to me that factors (eg sex)
        cannot be
           used as covariate/variable, which forces me to model
        them as a
           separate class although I’m not interested in sex
        differences.
           This brings me to the following FSGD file:


           # HcDis.fsgd

           GroupDescriptorFile 1

           Title HcDis

           Class Hc_Male

           Class Hc_Female

           Class Dis_Male

           Class Dis_Female

           Variables Age

           Input subjid1 Hc_Male 35

           Input subjid2 Dis_Female 30

           ….


           Then the difference between Hc and Dis, corrected for
        age and sex
           is given by the contrast matrix

           #Hc-vs-Dis.mtx

           0.5 0.5 -0.5 -0.5 0 0 0 0 0 0 0 0


           Is this correct?


           Best,

           Martijn





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-- 
Douglas N. Greve, Ph.D.
MGH-NMR Center
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