Hi Laura
 In the 
wikihttps://surfer.nmr.mgh.harvard.edu/fswiki/LinearMixedEffectsModelswe 
recommended to order the columns of the design matrix in thefollowing way: 
Column 1: theintercept term (which is a column of ones)
Colum 2: the timecovariate if it varies across subjects (eg. time from baseline)
Column 3-q: anytime-varying covariates (eg. training: 0 before training, 1 
aftertraining)
Column q+1-r: thegroup covariates of interest (eg. a binary variable 
indicatingwhether or not the subject is a patient), for n groups you will 
haven-1 binary covariates
Column r+1-s:interactions between group covariates with the 
time-varyingcovariates (only the interesting interactions)
Column s+1-p: anyother nuisance time-invariant covariates (eg. age-at-baseline, 
gender,etc...)

LME is a type oflinear regression model that integrates both a model for the 
mean anda model for the covariance into a single statistical model. So ifyou 
want to compare different models for the mean (with differentcovariates) then 
you need to start with a “maximal model for themean” that includes all the 
possible covariates of interest. Then you selectthe random effects for that 
"maximal model" using the model selectionprocedure with lme_mass_LR. Random 
effects can only be time-varyingcovariates (i.e a subset of the columns from 1 
to q above, thosecomprise the Zcols parameter in lme_mass_fit_vw)
After you choosewhich time-varying covariates are going to be considered as 
randomeffects then you can test if any single fixed effects covariate in your 
designmatrix has a significant contribution to the model in the same wayyou 
would for a traditional GLM. You will use F-tests for that.Covariates that do 
not significantly contribute to the model can beruled out of the model and a 
new model with less covariates but the same random effects can thenbe fitted. 
Keep in mind thatfitting lme models is computationally expensive and the 
computationoverhead quickly increases with the number of random effects and 
fixedeffects in your model.  Also considering one or two random effects 
including the intercept term (or atmost three) is usually enough but this 
really depends on the natureof the data. 

Best-Jorge


 
      De: Laura Rueda Delgado <laura.ruedadelg...@kuleuven.be>
 Para: Freesurfer support list <freesurfer@nmr.mgh.harvard.edu> 
 Enviado: Lunes 11 de abril de 2016 13:05
 Asunto: Re: [Freesurfer] LME for functional data, 3 factors
   
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div.yiv9346679664WordSection1 {}#yiv9346679664 Dear Martin,    Thank you for 
your quick response.    My research question is focused on the group and day 
effect, so I could simplify the model. From your response, I thought of 
including in the design matrix the binary code for Condition 2, and for 
Condition 3 in two columns, like you suggested; however, adding only the 
interaction effect of group and day. This way, the model takes into account the 
repeated measures of Condition while remaining relatively simple.    Now, to 
add more complexity and be more specific, I'm interested on neural correlates 
of learning, which is (un)fortunately tangled with performance. Therefore, I 
was thinking to add the learning gains (e.g. [performance_day_2 - 
performance_day_1]/performance_day_1) as a fixed effect. Checking the example 
datasets that come with the LME toolbox, I see that other measures (e.g. age, 
gender) are repeated for all the measures at different days of the same 
subject. And, when the age of participants at the first measurement is used as 
a fixed effect, "baseline age", the value is repeated for the baseline day and 
the other days. I was wondering if this could be applied for the Learning Gain 
as well (which is a measure of change of performance over the training days). I 
have my doubts because I would understand that this type of coding would 
describe two mixed aspects: a “prediction” of Gain from the brain data at Day 
1, along with the appropriate relationship of Gain with brain data at Day 2. I 
would think that adding 0s for Day 1 in the variable Gain would be more 
appropriate, and this way the fixed effect of Day would be coded in the 
variable Gain. But of course, I recur to the experts to settle this issue.    
Additionally, I see that I could compare two models with different number of 
random effects with lme_mass_LR. However, I would like to compare models with 
different covariates (other covariates of no interest, like gender and years of 
education). Is this possible within this toolbox?       Best regards,    Laura 
Rueda    From: freesurfer-boun...@nmr.mgh.harvard.edu 
[mailto:freesurfer-boun...@nmr.mgh.harvard.edu]On Behalf Of Martin Reuter
Sent: donderdag 7 april 2016 18:20
To: freesurfer@nmr.mgh.harvard.edu
Subject: Re: [Freesurfer] LME for functional data, 3 factors    Hi Laura,

1) 
you would need to model the 3 level variable differently, as 1,2,3 will be 
understood as continuous and that is not what you want. Instead you have two 
columns: one column for group 2, where all instances are binary (1 if group is 
2, else 0), and one for group 3. Then the intercept and slope will be for group 
1 and these columns contain the offsets for group 2 and 3 respectively.
About interactions, make sure you really want to model all interactions. Some 
may be not very meaningful and keeping the model simple is usually a good idea. 
But if you want them all, add them all.

2) Zcols: Vector with the indices of the colums of X that will be considered  
as random effects. Usually the intercept is a random effect and maybe other 
variables (e.g. the time, if you want to allow slopes to be different across 
subjects). For just the intercept column use [ 1]
ni should be correct

3) yes, but with the design above, since you model a global intercept and then 
the offset of each group (or whatever that three condition variable is) you 
need to make sure you interpret things correctly. E.g. a 1 in such a column for 
group 2 or three indicates that there is a difference from the first group. 
This is not the group 2 effect.

4) Sorry, I don't know. Maybe someone else has a suggest.

Since you have all interactions, you should be able to specify contrast 
according to your test in this model and don't need to create a new one. Your 
setup is a little complicated, so it would be wise to involve a local 
statistician to make sure you are interpreting things correctly.

Best, Martin


 On 04/07/2016 10:57 AM, Laura Rueda Delgado wrote: 
Dear FreeSurfers and LME experts,   I've just started using the LME toolbox by 
Bernal-Rusiel et al (2012, 2013) in Matlab, apart from FreeSurfer. My 
experimental design includes one between-subjects factor (group with two 
levels, 24 vs 22 subjects), and two within-subjects (WS) factors (day with two 
levels, and condition with three levels). As far as I understand, the LME 
toolbox can be used for longitudinal data and for investigating modulations of 
neural activity with behavioral measures. However, it's been difficult for me 
to set up both the design matrix and the input of the LME functions given three 
fixed factors in my design (I haven't included behavior yet). So I have a few 
questions that I hope you can help me answer. I follow these steps:   1) 
Following the wiki, I've created a pre-design matrix, M, with: First column: 
Day factor coded as 0 (first day) and 7 (7 days later, as during acquisition). 
Second column: Group factor binary coded. Third column: Condition factor coded 
with dummy variables 1 to 3 (three conditions in total). I don’t know if this 
is correct; I have failed to find in the mailing list any reference to an 
additional repeated measure besides time in LME models. From here, I've created 
the design matrix X adding a column of 1's for the intercept, adding the pre 
design matrix M, and adding columns for every possible interaction by 
multiplying element-wise the columns of M (including two-way and three-way 
interactions).   2) I then use lme_mass_fit_vw, but I have doubts about some 
inputs Zcols: column 1 in X ni: created a vector with 6 for all subjects (in 
total there are 6 repeated measures, 2 of day and 3 of condition) I kept the 
others as default.    3) lme_mass_F for statistics of fixed effects. I check 
main effects and interactions with contrasts based on the design matrix X: 
placing a 1 in the column position corresponding to each effect of interest.   
4) lme_mass_FDR2 for correcting the F stats for multiple comparisons. I would 
like to compare the results using AlphaSim's Monte-Carlo simulations, however 
I'm not sure what image to use to estimate the smoothness. Would you have a 
suggestion?   Could you please let me know if this procedure is sound? Also, if 
I’m interested in specific comparisons or post-hoc tests, e.g. Group 1$Day 
1$Condition 3 vs. Group 1$Day 2$Condition 3, would I need a separate model for 
that? And lastly, for the analysis including the behavioral measures, should I 
just include them as a forth column in the pre-design matrix M and add the 
relevant effects in X?   I hope I haven’t overwhelmed you with so many 
questions. I would greatly appreciate any suggestion you can provide.     Best 
regards,     Laura Rueda   


 _______________________________________________ Freesurfer mailing list 
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 --  Martin Reuter, PhD Assistant Professor of Radiology, Harvard Medical 
School Assistant Professor of Neurology, Harvard Medical School A.A.Martinos 
Center for Biomedical Imaging Massachusetts General Hospital Research 
Affiliate, CSAIL, MIT Phone: +1-617-724-5652 Web  : http://reuter.mit.edu  
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