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Dear all,

This is my first attempt to analyze longitudinal structural data with freesurfer, and I just do my best to follow the tutorial. I have some things not clear, so any help would be appreciated.

We have a longitudinal study design with 2 groups, healthy and patients who were scanned at baseline a second time following a variable time interval (6 to 36 months). We want to investigate whether the patient’s cortical thickness/volume progresses differently compared to controls (group-by-time interaction effects). I chose to analyze the data with LME due to variable follow-up time, having only 50% of the patients with a second scan, and also having family members within and between groups.

Questions 1) To account for familial relationship, should I add a family ID as covariate that stays in the design matrix X and count this covariate as random effect when the model is fitted? Like this: lhstats = lme_mass_fit_Rgw(X,[1 2 3],Y,ni,lhTh0,lhRgs,lhsphere);

Where the first 3 covariates in X are counted as random effects: 1 the intercept, 2 follow-up time and 3 family ID.

The X would further include group, age, sex, TIV, and group*time, the last one being the interaction term we want to assess using CM.C = [0 0 0 0 0 0 0 1].

Does the X and CM look good to address our research question?

2) It is unclear to me how to perform correction for multiple comparisons and assess what is significant. I follow this procedure after constructing X:

[lhTh0,lhRe] = lme_mass_fit_EMinit(X,[1 2 3],Y,ni,lhcortex,3); [lhRgs,lhRgMeans] = lme_mass_RgGrow(lhsphere,lhRe,lhTh0,lhcortex,2,95); lhstats = lme_mass_fit_Rgw(X,[1 2 3],Y,ni,lhTh0,lhRgs,lhsphere); F_lhstats = lme_mass_F(lhstats,CM); dvtx = lme_mass_FDR2(F_lhstats.pval,F_lhstats.sgn,lhcortex,0.05,0):

The dvtx is not empty but has 130 vertexes that survive. What I don’t understand, when constructing the sig.mgh map it appears the dvtx is not used: fs_write_fstats(F_lhstats,mri,'sig.mgh','sig'); How can I be sure when I import sig.mgh in Freeview I only look at the vertexes surviving multiple comparison?

3) Given a few clusters showing an interaction effect which are saved as sig.mgh and overlaid on surface in freeview, how do I know (visualize) what is going on in these clusters, like which of the group means go up or down? (I use FS71 and tksurfer not working). Is it here that printing out and plotting the betas (of the interaction term) are useful for?

4) I have a hypothesis to find differences in prefrontal cortex, at which step would I apply a PFC mask? I have constructed a PFC.label file by adding corresponding label files.

Thank you, Julian