Dear Vlad,

as far as I understand covariates and paired t-tests, it does not make much 
sense to include a covariate per subject unless you have two different 
assessments of that covariate for each time point (pre and post drug 
treatment). Put differently, a paired t-test is the same as testing the 
difference of pre and post against zero, which is the same as a one sample 
t-test. When you then include the covariate and this does not change from pre 
to post within each subject, then you would enter a column of zeros as 
covariate, which his not what you want.

By the way, including TD as a covariate in a one sample t-test for instance, 
does not show you the impact of TD on the BOLD contrast. It would show you 
where in the brain the BOLD contrast deviates from zero, which canNOT be 
explained by TD. Covariates are always of no interest.

What you can do is to calculate a simple regression, which is actually the way 
how calculate "covariates of interest". When you have only one TD value per 
subject you can define three simple regressions:
1) TD and pre-treatment scan
2) TD and post-treatment scan
3) TD and difference of pre- and post-treatment scans (using e.g. imcalc)

The third one would be the model you want to examine.

In case you have different TD values for pre- and post-scans you can do more 
or less the same:
1) TDpre and pre-scans
2) TDpost and post-scans
3) TDpost-TDpre and (post-scans)-(pre-scans)

Good luck,

On Tuesday 23 September 2008 15:19, Vlad Kushnir wrote:
> Hello,
> I have encountered a problem and would greatly appreciate some direction in
> resolving it.
> In my study design there are two drug conditions, Pre and Post-drug scans.
> During each scan subjects are presented with a task that shows drug-related
> and neutral cues, as well as a rest fixation cross in a blocked design. As
> I have one subject group and the subjects vary in their level of tobacco
> dependence (TD), my goal is to create a model that examines how TD
> influences differential activation between the two scan sessions.
> Therefore, in essence I would like to create a paired-samples t-test with
> TD as a covariate of interest.
> So far I have tried the following:
> To best look at how drug cues elicit brain activation in my population of
> interest, for every subject during each of the two scans, I have created a
> 1st level drug cue > neutral cue contrast. These contrasts were later taken
> into a 2nd level paired t-test design (with TD as a covariate for each
> pair), however the job would not compute. Iím wondering if there is a way
> to look at the effect of TD on the difference between the two scans, or as
> a covariate of interest.
> Then I tried creating a full factorial design with one factor (Drug) that
> has two levels (pre and post). There was no independence between the two
> levels. TD was the covariate, but it was entered twice repeatedly, once for
> the pre-drug level and once for the post-drug. I am not sure if this is the
> most appropriate design.
> In an alternative method, I took every subjectís pre and post drug scans
> into 1st level and created a drug cue pre > drug cue post (and vice versa)
> contrast. I then took these contrast images into a 2nd level multiple
> regression analysis, where TD was the covariate. I am also not sure if this
> is the most appropriate design, especially since neutral cues are not taken
> into context.
> Please advise.
> Thank you in advance,
> Vlad Kushnir

Thilo Kellermann
Department of Psychiatry and Psychotherapy
RWTH Aachen University
Pauwelsstr. 30
52074 Aachen
Tel.: +49 (0)241 / 8089977
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