Dear FSL experts,

I have pre and post-intervention data for a group of patients, and I'd like to use VBM to look at the post-pre GMV difference. I've computed a 4D "difference" image with all subjects merged, as suggested here.

However, the heterogeneity among these pathological brains made me wonder whether there'd be any sense to doing a VBM-like analysis within-subjects, since the group-level analysis might mask effects due to e.g. overly-warped registrations. I had in mind papers that plot a colour-map indexing the number of subjects that show a certain effect at the first-level analysis. However, I'm not sure in the case of VBM one can actually talk of a first-level analysis, since there is no statistical significance to compute within-subjects, as one can with time-series data (fMRI).

Another problem, of course, is that an arbitrary threshold would have to be defined (in terms of pre-to-post effect size) within individual subjects, to be applied across my 4D "difference" image. Would it make any sense at all to define such a threshold, one beyond which the pre-to-post change in GMD within a subject is "non-negligible", or would that be a complete hand-wave? 

Any thoughts on this would be much appreciated, thanks!

Tudor