Dear SPMers
We would highly appreciate your comment/advice on the following VBM
questions. 
We compared GM segmentations between patients with depression and controls
using the Christian Gaser cg_create_template and cg_vbm_optimised VBM
scripts. We used the final GM outputs additionally modulated by the Jacobian
determinants of the deformation fields. 
In our first analyses creation of study specific templates and GM
segmentations were computed with normalisation option set to "preserve
total". The final results indicated a clear reduction of GM volume in the
right parahippocampal area for the patients. 
In a subsequent analysis we repeated cg_create_template and
cg_vbm_optimised, but now with "preserve concentration", the common choice
for VBM. Unfortunately, however, the interesting hippocampal volume effect
almost completely vanished.
To our understanding what happens if we run the cg scripts with "preserve
total":
- In cg_create_template the normalised T1 MRIs of each individual are
modulated based on the GM deformation parameters. The modulated T1s are then
segmented using the standard .mnc priors. After averaging across individuals
a modulated T1 template and GM, WM and CSF priors are obtained. The priors
are probability maps, so in essence they do not contain modulations
themselves. However, since they are derived from the modulated T1's they are
probably slightly different than with normalisation set to "preserve
concentration".
-In cg_vbm_optimised the T1 MRIs in native space are normalised and
modulated based on the GM transformation parameters. Then the modulated
images in MNI space are segmented, using our custom, modulated, T1 template
and GM, WM, CSF priors. Again the resultant segmentations will in fact not
be modulated, but probably somewhat different compared to the situation when
using "preserve concentration". Finally we select the GM and explicitly
modulate it by the Jacobian matrix field. It is this modulated GM we finally
analyses.
So, we guess that by selecting "preserve total" and doing an additional
Jacobian modulation. We actually do not perform a modulation twice. However,
the GM segmentation results may differ somewhat when using either "preserve
total" or "preserve concentration". Taking it one step further. The
hippocampal volume effect is clearly present only in the explicitly
modulated but not in the unmodulated output from cg_vbm_optimized with
"preserve total". Therefore it may be argued that the volume effect is
encoded in the GM deformation fields. This field is computed by first
aligning the GM prior to the original MRIs in native space, then segmenting
the GM and finally compute the normalisation from GM in native space to the
GM prior. Therefore it seems that the different results from the cg scripts
with "preserve total" or "preserve concentration" may be primarily due to a
difference in the GM prior (though we did not test this yet).
With regard to this we have the following questions:
-What could explain the effect to vanish when "preserve concentration"
instead of "preserve total" is used? Is it because of the difference in the
segmentations (priors), only? 
- By selecting "preserve total" we may have introduced a spurious result. On
the other hand, looking at the bright side of life, we may have enhanced the
sensitivity of our VBM analyses. Could there be any arguments to support the
latter?
- Is our initial analysis running the cg scripts with "preserve total" still
scientifically valid?
Best wishes,
Dennis van 't Ent, Dept. Department of Biological Psychology, Vrije
Universiteit Amsterdam, The Netherlands
Dick Veltman, Department of Psychiatry and Radiology, VU medical centre,
Amsterdam, The Nertherlands