Dear Experts,

I have seen this question pop up a few times in the forum, but have not seen a clear response, so I was wondering if someone might be able to clarify or offer their opinion.

1. Do the hippocampal subfields and amygdala nuclei need to be corrected for ICV (either by including ICV as a covariate or taking the ration if each subfield to the ICV)?
2. If so, might it make more sense to correct them (perhaps take the ratio of each subfield to the hippocampus) for the volume of the hippocampus (after the hipp. itself has been corrected for the ICV)? If the correction is recommended, I am wondering about whether the second option might be better, because the ICV correction might be introducing too much variability for such a small sub-structure, whereas, correcting for just the hippocampus volume might be a bit more accurate.

I found two ways of dealing with this in the relevant papers for the hipp. Subfield and amyg nuclei, respectively, quoted below:

“Then, we correct these estimates for age and intracranial volume (ICV) by regressing them out with a general linear model. This step is important because the subregion volumes are strongly correlated with these two variables, which can easily confound the analysis – subjects with large ICV and/or of younger age are expected to have larger hippocampi; see for instance (Mueller, Schuff, Yaffe, Madison, Miller, & Weiner, 2010). Moreover, such correction was used in (Mueller, et al., 2013), so we used this correction as well in order to directly compare the results” (Iglesias, 2015)

“ICV was added as a covariate to all ANOVAs” (Saygin, 2017)

I would love to hear any advice/perspective.

Thank you in advance.

Arkadiy