Hi Woo-Suk
Just adding to Bruce's reply: area isn't a "technically more noisy and usually thus less sensitive" as the reviewer suggests. Area isn't noisier on its own right, and it's measured from the very same surfaces from which thickness is measured. However, there is a much larger variability of area across subjects than of thickness, even within the normal range, such that the variance of volume, that can be explained by or associated with other indices, is largely explained by the variance in area. The first paper that (as far as I know) showed this is Voets et al. (Neuroimage, 2008), and we keep observing this repeatedly in different datasets, published or not.
About the Schmaal et al. paper (Molecular Psychiatry, 2016): it is an excellent paper in which the authors didn't spend time (or space) discussing volume, going instead straight to the more interesting bits: area and thickness.
All the best,
Anderson
On 29 August 2016 at 13:56, Bruce Fischl fischl@nmr.mgh.harvard.edu wrote:
Hi Woo-Suk
why not just do the surface analysis that they are requesting? I'm not sure what you are asking, but certainly volume = surface area * thickness in general, and so a volumetric effect can be driven by one or both of surface area and thickness
cheers Bruce
On Sat, 27 Aug 2016, Woo-Suk Tae wrote:
Dear FreeSurfer experts and developers
I am confronted with some technical question of a reviewer. I am not sure about "volume = thickness-by-surface area" and the review's opinion (attached below) about volume, surface area, and thickness was correct. Any comments from FreeSurfer's experts would help me.
Sincerely yours
Woo-Suk Tae Seoul, Korea
I added the reviewer's comments.
- Volume/thickness: The authors cite many papers that show volume and
thickness differences in MDD. The unresolved part here, however, is the RELATION between cortical thickness and cortical volume: There is no doubt, that both measures are found affected in MDD. This is, because cortical thickess multiplied by the surface area of a gyrus results in its volume, so volumse = thickness-by-surface area. Surface area values themselves are technically more noisy and usually thus less sensitive (due to the problem of false attributions to an area).
So, volume is influenced by thickness and surface and is the less specific measure. If a volume effect is detected in a study, it is unclear, if it is driven by thickness, or surface area, or both. In this respect, the study of Schmaal et al. is telling, as it analyzed BOTH measures, finding only thickness effects of MDD, and (practically) no surface area changes except for adolescent MDD. In the adolescent MDD samples gross surface area differences were detected.
This means, that the question of "superiority" is rather a question of "specificity": (Cortical) volume findings in adult MDD are mostly driven by thickness differences and are in on way independent from thickness differences. In this respect, the authors should follow the basic geometric principles of morphometry and point out the relatedness of the two. They can simply check this in their FreeSurfer variables (e. g. for total grey matter volume). Not reporting surface area is leaving an interpretational gap as surface area differences could in addition drive volume differences. The authors may want to decide not to present surface area results, but then they should discuss this as limitation to disentangle the origin of volumetric (cortical) effects. This seems important as methylation effects and FKBP5 interact with early life time stress, so effects on surface area as seen in adolescent MDD highlight that surface area effects could play in.
Woo-Suk, Tae Ph.D. Research Professor Brain Convergence Research Center, Medical Research Center Anam Hospital, Korea University Medical Center, Seoul, Korea mobile: 82-10-9120-4629 office: 82-2-920-6831 email: woosuk.tae@gmail.com, woostae@gmail.com
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