I did not mean that. If there is an interaction then there are issues of interpretation when comparing means (ie, offsets) since the comparison then depends on the value of the covariate. Eg, at age 70 there may be no difference in offsets, at age 50 there may be a positive, then negative at age 90. The way you have it set up the comparison will take place at the sample mean. These issues does not stop most of the community from doing this type of test. You can probably get it published, you just need to be clear what you are doing and what the limitations are.

doug

On 12/24/14 4:47 PM, maaike rive wrote:
Hi Doug,

Thank you for your quick response. Concerning question3, do you mean that if there is an interaction with age, it is all right to use DODS (without stratification)?

Thanks,
Maaike

------------------------------------------------------------------------
Date: Wed, 24 Dec 2014 15:31:53 -0500
From: gr...@nmr.mgh.harvard.edu
To: freesurfer@nmr.mgh.harvard.edu
Subject: Re: [Freesurfer] DODS design and demeaning


On 12/24/14 5:21 AM, maaike rive wrote:

    Dear Freesurfer experts,

    I would be very greatful if you could help me with three (probably
    basic) questions regarding an mri_glmfit design.

    For the design and contrasts I used FSGDF. I have a 2x2 factorial
    design with one covariate (age). I specified all four groups
    (A1B1, A1B2, A2B1, A2B2) and the covariate in one model, because I
    would like to test for the interaction between A and B (regressing
    out the effects of age). Age was demeaned using the mean of all
    subjects (i.e. of all 4 groups).

    My first question regards the contrasts:
    If, besides the interaction and main affects of A and B, I would
    like to assess the difference between individual groups, for
    example A1B1 - A1B2, is it okay to use the same model (1 -1 0 0 +
    further 0's for the age regressors); or should I make a new FSGDF
    containing only the subjects of group A1B1 and A1B2?

It is a tricky question. You will get the same group means regardless of whether you combine all subjects or use a 2nd FSGD. The difference will be that you will have a much higher DOF if you combine them all. This means that the noise in the other subjects informs you about the noise in those two groups. If you can justify this, then you can leave them combined. If the 2nd model gives you the results you want, then reporting that would be a stronger scientific result.


    My second question is associated with the first:
    If it is allowed to use the same model, how does freesurfer deal
    withdemeaning? Since I used the mean of all subjects to demean and
    not just of the subjects of for example A1B1 and A1B2.

The demeaning is also tricky. I would actually test whether there is an interaction between group and age. If there is no interaction, then I would re-run using a DOSS model in which case the demeaning won't make a difference.


    My third question regards the DODS/DOSS issue.
    I used DODS, because I do not believe the slopes of age by volume
    (or age by area/thickness) will be exactly parallel between
    groups. I tested this also be using contrasts of the age
    regressors, (for example using the contrast 0 0 0 0 1 -1 -1 1 for
    a AxBxage interaction) and indeed there are interactions with age
    in some brain areas. For thickness, they were FDR corrected still
    significant, for other measeurs the were not significant after
    correction, but that seems natural given the sample sizes. No I
    wondered whether it would suffice to use a DODS design (since
    slopes differ between groups) or whether I should stratify groups
    further for age (for example use two models, one for young
    subjects, on for old subjects). If the latter is the case, I would
    end up with very small samples, I am afraid.

If there is no interaction in the areas that show up in your contrast of interest, then it is safe to use DOSS. If there are, then I don't think that stratifying them solves the problem.

doug


    Thanking you in advance,

    Maaike


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