I have this interesting situation. I understand its important to include ICV as a covariate while conducting cortical volume (CV) analysis.

So for my clinical sample (CL) vs healthy-controls (HCs):

1. If I do network-wise analysis (i.e., after parcellating the whole brain into 17 networks), I get highly significant differences in CV (MANCOVA: CL < HCs) for a specific network (say N1) - if I include ICV as a covariate, but not otherwise.

2. If I do whole-brain vertex-wise analysis, I get highly significant differences in CV (CL < HCs) for a specific cluster (which is overlapping with an area of N1) - if I do not include ICV as a covariate, but not otherwise.

I am not sure how to interpret this i.e., ICV as a covariate for network-wise analysis plays an opposite role i.e., makes my findings stronger compared to ICV as a covariate for whole-brain vertex-wise analysis i.e., makes my findings weaker. Does ICV as a covariate add some kind of noise during whole-brain vertex-wise analysis?

I would really appreciate any help in understanding this.