Hi all,

Is using forced permutation for non-orthogonal design matrices wrong or is it 
allowed to do this instead of using tools like palm (what happens eg with the 
covariates when using forced permutation)? I used forced permutation  and it 
seemed to work, results were (partly) comparable to what I found with monte 
carlo simulations.


Thanks, Maaike

________________________________
Van: freesurfer-boun...@nmr.mgh.harvard.edu 
<freesurfer-boun...@nmr.mgh.harvard.edu> namens Harms, Michael 
<mha...@wustl.edu>
Verzonden: vrijdag 26 augustus 2016 01:00:13
Aan: Freesurfer support list
Onderwerp: Re: [Freesurfer] mri_glmfit-sim permutation testing running after 3 
days!


Hi,
You might want to check out FSL’s PALM tool, which has a bit more sophisticated 
permutation framework, and allows for permutation in the context of 
non-orthogonal covariates.

cheers,
-MH

--
Michael Harms, Ph.D.
-----------------------------------------------------------
Conte Center for the Neuroscience of Mental Disorders
Washington University School of Medicine
Department of Psychiatry, Box 8134
660 South Euclid Ave. Tel: 314-747-6173
St. Louis, MO  63110 Email: mha...@wustl.edu

From: 
<freesurfer-boun...@nmr.mgh.harvard.edu<mailto:freesurfer-boun...@nmr.mgh.harvard.edu>>
 on behalf of Ajay Kurani 
<dr.ajay.kur...@gmail.com<mailto:dr.ajay.kur...@gmail.com>>
Reply-To: Freesurfer support list 
<freesurfer@nmr.mgh.harvard.edu<mailto:freesurfer@nmr.mgh.harvard.edu>>
Date: Thursday, August 25, 2016 at 4:13 PM
To: Freesurfer support list 
<freesurfer@nmr.mgh.harvard.edu<mailto:freesurfer@nmr.mgh.harvard.edu>>
Subject: Re: [Freesurfer] mri_glmfit-sim permutation testing running after 3 
days!

Hi Doug,
   Thanks for the help!  I think I figured out the issue based on your response.
1) I created a template to use for this group and named it fsaverage (including 
creating monte carlo simulations) for simplicity of integrating with freesurfer 
as I am newer to it.  This is why the sizes didn't match up as you expected
    but the mri_glmfit still ran.

2) I deleted the folder and restarted without background processes.  The error 
became apparent.  Of my covariates (2 fix factors and 3 quantitative), not all 
were orthogonal.  In looking at the error more, it seems that i need to add the
--perm-force if I wanted the simulation to run, however the background 
processes were not aware of this error and kept polling as you mentioned.

This brings me to a new but related issue.  From what I have read in other 
freesurfer posts, it is statistically incorrect to use --perm-force for 
non-orthogonal covariates (or continuous covariates).  I am unsure how to 
proceed.
a) If I ran permutation testing (to overcome the issue of incorrect smoothness 
estimations from the gaussian distribution assumption), then I run into the 
issue of non-orthogonal covariates.  Is there a way to orthogonalize the data in
    freesurfer, or a solution to this issue?

b) If orthogonalizing is difficult to implement, another option is running Qdec 
with the montecarlo simulation at a more conservative p value (p< 0.001).  From 
your previous posts, the testing at this p value for 10mm seems to meet the 5% 
FPR.  One question is if the non-orthogonal data affects this analysis as well 
for this model?

Thanks,
Ajay

On Thu, Aug 25, 2016 at 12:18 PM, Ajay Kurani 
<dr.ajay.kur...@gmail.com<mailto:dr.ajay.kur...@gmail.com>> wrote:
Hi Freesurfer Experts,
   I am trying to use freesurfer's mri_glmfit-sim tool to run permutation 
testing on cortical thickness data (as recommended by Doug in my previous post: 
http://www.mail-archive.com/freesurfer%40nmr.mgh.harvard.edu/msg48653.html )

Most of the tutorials I found were not related to permutation testing so the 
subsequent steps may be incorrect.  Please let me know where I go wrong...

1) I first ran QDec to generate a folder for the analysis which would create 
the subsequent fsgd and y files needed my mri_glmfit-sim.  I am running both 
left and right hemisphere cortical thickness analysis with 10mm smoothing.  The 
following is for just the left hemisphere.   Note I am doing a 3 group 
comparison, but for this 2 group ttest I manually centered the data based on 
the 3 group mean for age and education.

2) I ran the following command:
/mri_glmfit-sim --glmdir ./HCvsPAT_lh_thickness_10mm/ --sim perm 10000 2 
perm.abs.2 --sim-sign abs --bg 16

Prior to running the command above, from the y.fsdg file I deleted the fwhm 
estimate of 13mm since this was not correctly estimated (ACF with long tails).  
I assumed that by removing this estimate, it would force the permutation test 
to calculate based on the data but when looking at the log output I see the 
following which says fwhm 0:

cmdline mri_glmfit.bin --C 
./HCvsPAT_lh_thickness_10mm//tmp.mri_glmfit-sim-19468/lh-Avg-Intercept-thickness.mtx
 --C 
./HCvsPAT_lh_thickness_10mm//tmp.mri_glmfit-sim-19468/lh-Diff-Male-Female-Intercept-thickness.mtx
 --C 
./HCvsPAT_lh_thickness_10mm//tmp.mri_glmfit-sim-19468/lh-Diff-PD-MCI-Intercept-thickness.mtx
 --C 
./HCvsPAT_lh_thickness_10mm//tmp.mri_glmfit-sim-19468/lh-X-Gender-Group-Intercept-thickness.mtx
 --sim perm 625 2 ./HCvsPAT_lh_thickness_10mm//csd/perm.abs.2.j013 --y 
/home/akurani/Documents/PPMI/FS_Final/qdec/HCvsPAT_lh_thickness_10mm/y.mgh 
--mask ./HCvsPAT_lh_thickness_10mm//mask.mgh --sim-sign abs --fwhm 0 --fsgd 
./HCvsPAT_lh_thickness_10mm//y.fsgd dods --surf fsaverage lh white --sim-done 
./HCvsPAT_lh_thickness_10mm//csd/poll/done.perm.abs.2.j013

3)I started this a few days ago on a 16 core machine and it is still running in 
the terminal.  I have 150 subjects in the analysis and specified 10000 
iterations.  In the terminal I assumed when I reach Poll 10000 it would be 
complete but currently I am at : Poll 13341 job 1 Thu Aug 25 12:03:51 CDT 2016

Questions:
a) I am curious, is this going to run 10,000 simulations X 150 patients or does 
the Poll number not have anything to do with the number of iterations it is on?


b) Did I run this procedure correctly?  Was I incorrect in deleting the fwhm 
estimate from y.fsgd file generated by Qdec even though we know the estimate is 
incorrect since smoothness assumed a gaussian distribution as opposed to 
gaussian with heavy tails

c) I noticed in the logfile the following warning:
INFO: gd2mtx_method is dods
Computing normalized matrix
Normalized matrix condition is 5.65727
Matrix condition is 935.597
Found 136777 voxels in mask
Reshaping mriglm->mask...
search space = 89675.729228
ERROR: design matrix is not orthogonal, cannot be used with permutation.
If this something you really want to do, run with --perm-force
Poll 2 job 1 Tue Aug 23 22:58:18 CDT 2016

I am not sure if this means my simulation is incorrect?

Thanks,
Ajay


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