Hi Gallen, 

please find my response inline. 

Hope this helps,

Kersten

-----Original Message-----
From: "Gong, Liang" <lgo...@mgh.harvard.edu>
Reply-to: Freesurfer support list <freesurfer@nmr.mgh.harvard.edu>
To: Freesurfer@nmr.mgh.harvard.edu <Freesurfer@nmr.mgh.harvard.edu>
Cc: mreu...@nmr.mgh.harvard.edu <mreu...@nmr.mgh.harvard.edu>
Subject: [Freesurfer] About the contrast matrix in LME toolbox
Date: Thu, 28 Dec 2017 00:03:35 +0100

Dear LME developer and expert,

I am using LME recently, based on longitudinal brain structural data,
but I have two confusions in using it.

1)      I followed the tutorial at: https://surfer.nmr.mgh.harvard.edu/
fswiki/LinearMixedEffectsModels
However, I don’t actually understand the Contrast matrix design in this
tool. In the example the contrast C matrix is a 3*14, is there any
explain about this matrix design?

The contrast matrix creates linear combinations of the estimated
parameters (betas) by assigning a weight (typically +1, 0, or -1) to
the entry corresponding to that parameter. These linear combinations
are used to formulate and test hypotheses about the effects of
interest.

For the given univariate example, the columns of the contrast matrix
correspond to the intercept (1), the main effect of time (2), the main
effects of group and their interactions with time (3-8) and several
covariates of no interest and possibly their interactions with time (9-
14). The global test ("Is there at least one difference between any
pair of groups?") is broken down into three single comparisons, and
this is reflected by each row.

For my study, I want to explore 3 treatment (2 therapy methods and 1
waitlist) effects on the brain structural, If I want to explore the
main effect of treatment, how could I write the Contrast matrix, and
whether I can explore each treatment effect on the brain structural?
And how can explore the time*treatment effect contrast matrix?

Your contrast matrix could have the following columns:

1. Intercept
2. Time
3. Therapy 1 group
4. Interaction of therapy 1 group with time 
5. Therapy 2 group
6. Interaction of therapy 2 group with time 

This matrix implies that we use "waiting list" as the reference
category. You could add further columns for covariates such as age-at-
baseline, gender, ICV, etc. I also assume that therapy 1, therapy 2,
and waiting list do not have any overlapping patients, i.e. are
distinct groups. 

To explore the main effect of treatment group it is statistically
sufficient to ask: Is there a difference between waiting list and
therapy 1, and is there a difference between therapy 1 and 2. This
means that your contrast matrix for the global test of the main effect
of treatment group will have two rows: in the first row, set column 3
to +1, and in the second row, set column 5 to +1 and column 3 to -1. 

Since you only have three groups, while the univariate example has four
groups, this means that you can remove columns 7 and 8 of the example's
contrast matrix. For the same reason, you can also drop the third row
of the contrast matrix.

Next, to explore differences between treatment groups separately, there
are three possible tests: you can test therapy 1 group vs therapy 2
group, and either therapy group against the waiting list group. For
this purpose, use three contrast matrices each with a single row.
Assuming the above order of columns 1 to 6, set column 3 to +1 for
therapy 1 vs waiting list. Alternatively, set column 5 to +1 for
therapy 2 vs waiting list. Or, set column 3 to +1 and column 5 to -1
for therapy 1 vs therapy 2. All columns that are not explictly
mentioned here should be set to zero.

To test single interactions between treatment and time, i.e. the
differences in slopes, you can proceed in the same way, but use columns
4 and 6 instead of columns 3 and 5.

Needless to say, to assess the effect of therapy, you are primarily
interested in the differential change across time (if the first
measurement was done prior to therapy; i.e. pre-post therapy), not in
overall differences of groups (which are undesirable). This of course
means that the interaction of group and time, using columns 4 and/or 6
of the above contrast matrix, is much more relevant the simple group
comparison using columns 3 and/or 5.

Finally, note that in the LME toolbox, all above tests are F-tests.


2)      For the mass-univariate analysis, the example C matrix is 3*17,
and it will explore the group differences in the rate of change over
time among the four groups, and if I get the four group difference
maps, How can I know the difference between each two groups? If I need
to do the another qdec file and do the following steps as mris_preproc
and mri_surf2surf?

The difference between the 3*17 matrix in the mass-univariate example
and the 3*14 matrix in the univariate example is that there are four
additional predictors - one quadratic effect of time, and three
quadratic time * group interaction effects - and one removed predictor
(ICV, which does not make much sense for thickness analyses). It is
possible, but not necessary to use quadratic terms. In that sense, one
might equally use a simpler 3*13 matrix for the given example.

The difference between each two groups across time, i.e. the difference
in their slopes, can be tested in the same way as in the univariate
example and as explained above. No additional processing is necessary.



Thank you very much!
Best,

Gallen


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