I have a question regarding vertex-wise analysis using FreeSurfer. In my current analysis, I’m looking at the effects of an independent variable on cortical thickness and surface area across the brain.

I understand that for ROI-based surface area analyses, it is typically recommended to control for total brain volume (TBV) or intracranial volume (ICV), as surface area is correlated with these global brain size measures. However, I’m unsure whether this recommendation applies to vertex-wise analyses as well or whether any underlying preprocessing steps in FreeSurfer account for brain size differences automatically.

Could you please advise on whether TBV or ICV should be included as covariates in vertex-wise surface area models? And more broadly, under what circumstances is it advisable to control for global brain size in vertex-wise analysis?

Any insights would be greatly appreciated.

Best,

Muskan