Dear All,

I have a question that has recently come up in a discussion. Background 
is, we are doing a VBM study of three groups, say A/B/C. We want to 
perform an analysis on "modulated" GM maps, as derived by a DARTEL 
procedure. As such, it is usually recommended to include a global 
covariate, either total GM volume or total intracranial volume, as a 
covariate. Our groups, however, due to the nature of the underlying 
condition, have different globals, i.e., group A has higher globals than 
group B and/or C.

I understand that including the globals will change the interpretation 
of the resulting group differences. It may also, due to the group 
difference in the globals, "take away" some effects that may exist 
between the groups because the variance may be shared.

One idea that then came up was whether it is possible to use an 
orthogonalization on total GM / TIV, w.r.t. group status. This seemed 
like a worthwhile idea at the time as the aim was to not explain group 
differences by this orthogonalized variable that are already explained 
by group. We tried it and the effect was substantial, to say the least.

I am not sure, though, that this is a good (or even valid) idea from a 
statistical point of view. For one, I have seen several mails in the 
archives that mention that othogonalization of a nuisance variable is 
not a good idea. One could of course argue that it is not really a 
nuisance variable, it "only" changes the interpretation of the results 
by (interpreted in a very naive way) rescaling. But then again, I could 
be totally wrong and not see the forest for the trees. So as always, 
your insights into this matter are much appreciated.


Prof. Dr. med. Marko Wilke
  Facharzt für Kinder- und Jugendmedizin
  Leiter, Experimentelle Pädiatrische Neurobildgebung
  Abt. III (Neuropädiatrie)

Marko Wilke, MD, PhD
  Head, Experimental Pediatric Neuroimaging
  University Children's Hospital
  Dept. III (Pediatric Neurology)

Hoppe-Seyler-Str. 1
  D - 72076 Tübingen, Germany
  Tel. +49 7071 29-83416
  Fax  +49 7071 29-5473
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