By "wrong" I meant that permutation no longer  gives exact p-values in 
expectation with non-orthogonal designs. There is no theory to 
characterize the accuracy of  Freeman-Lane of the other methods. In this 
sense, they are not approximations but ad hoc methods that people hope 
do a better job than parametric methods. Anderson tested them on a wide 
range of designs, but it was, of course, not exhaustive. The accuracy of 
his results may not extend to other designs, so it is a buyer-beware 
situation (as with all neuroimaging).


On 8/29/16 10:16 PM, Harms, Michael wrote:
> Hi,
> I wouldn’t say that non-orthogonal designs are “wrong” to use with
> permutation.  Rather, there are different approaches to handling that
> situation and produce approximate p-values.  See Table 2 in Winkler’s 2014
> paper, and the results therein comparing the various approaches:
>
> http://www.ncbi.nlm.nih.gov/pubmed/24530839
>
>
> PALM actually gives you control over the method used, with the default
> (and recommended) approach being that of “Freedman-Lane", which is the
> same approach used by FSL’s ‘randomise’ tool to handle correlated
> 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  63110Email: mha...@wustl.edu
>
>
>
>
> On 8/29/16, 7:49 PM, "freesurfer-boun...@nmr.mgh.harvard.edu on behalf of
> Matt Glasser" <freesurfer-boun...@nmr.mgh.harvard.edu on behalf of
> m...@ma-tea.com> wrote:
>
> PALM handles GIFTI and CIFTI data.
>
> Peace,
>
> Matt.
>
> On 8/29/16, 6:21 PM, "Douglas N Greve"
> <freesurfer-boun...@nmr.mgh.harvard.edu on behalf of
> gr...@nmr.mgh.harvard.edu> wrote:
>
>> Does PALM do surface-based? Also, there is no way to appropriately
>> handle this. For permutation, non-orthogonal designs are wrong. There
>> are ways to try to compensate for it, which is what PALM is doing. Sorry
>> to be nit-picky!
>>
>>
>> On 08/29/2016 06:12 PM, Harms, Michael wrote:
>>> Hi Maaike,
>>> Why not just use PALM?  Then you don¹t have to worry about this (since
>>> PALM appropriately handles the situation of correlated 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  63110Email: mha...@wustl.edu
>>>
>>>
>>>
>>>
>>> On 8/29/16, 4:45 PM, "freesurfer-boun...@nmr.mgh.harvard.edu on behalf
>>> of
>>> Douglas N Greve" <freesurfer-boun...@nmr.mgh.harvard.edu on behalf of
>>> gr...@nmr.mgh.harvard.edu> wrote:
>>>
>>> It is hard to say. Since the subjects are not exchangeable, the
>>> permutation is technically not appropriate. Check the winkler paper,  I
>>> think he talks about what happens if you just don't do anything.
>>>
>>>
>>> On 08/29/2016 11:07 AM, maaike rive wrote:
>>>> 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 FSL¹s 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  63110Email: 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.ht
>>>> ml
>>>>
>>>>
>>>> <http://www.mail-archive.com/freesurfer%40nmr.mgh.harvard.edu/msg48653.h
>>>> tm
>>>> l>
>>>>       )
>>>>
>>>>       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-t
>>>> hi
>>>> ckness.mtx
>>>>       --C
>>>>
>>>>
>>>> ./HCvsPAT_lh_thickness_10mm//tmp.mri_glmfit-sim-19468/lh-Diff-Male-Femal
>>>> e-
>>>> Intercept-thickness.mtx
>>>>       --C
>>>>
>>>>
>>>> ./HCvsPAT_lh_thickness_10mm//tmp.mri_glmfit-sim-19468/lh-Diff-PD-MCI-Int
>>>> er
>>>> cept-thickness.mtx
>>>>       --C
>>>>
>>>>
>>>> ./HCvsPAT_lh_thickness_10mm//tmp.mri_glmfit-sim-19468/lh-X-Gender-Group-
>>>> In
>>>> tercept-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.m
>>>> gh
>>>>       --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
>>>>
>>>>
>>>>
>>>> ------------------------------------------------------------------------
>>>>
>>>> The materials in this message are private and may contain Protected
>>>> Healthcare Information or other information of a sensitive nature. If
>>>> you are not the intended recipient, be advised that any unauthorized
>>>> use, disclosure, copying or the taking of any action in reliance on
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>>>>
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>>> --
>>> Douglas N. Greve, Ph.D.
>>> MGH-NMR Center
>>> gr...@nmr.mgh.harvard.edu
>>> Phone Number: 617-724-2358
>>> Fax: 617-726-7422
>>>
>>> Bugs: surfer.nmr.mgh.harvard.edu/fswiki/BugReporting
>>> FileDrop:https://gate.nmr.mgh.harvard.edu/filedrop2
>>> www.nmr.mgh.harvard.edu/facility/filedrop/index.html
>>> Outgoing:ftp://surfer.nmr.mgh.harvard.edu/transfer/outgoing/flat/greve/
>>>
>>> _______________________________________________
>>> Freesurfer mailing list
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>>>
>>>
>>> The information in this e-mail is intended only for the person to whom
>>> it
>>> is
>>> addressed. If you believe this e-mail was sent to you in error and the
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>>> contains patient information, please contact the Partners Compliance
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>>> http://www.partners.org/complianceline . If the e-mail was sent to you
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>>> but does not contain patient information, please contact the sender and
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>>>
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>>>
>>> ________________________________
>>> The materials in this message are private and may contain Protected
>>> Healthcare Information or other information of a sensitive nature. If
>>> you are not the intended recipient, be advised that any unauthorized
>>> use, disclosure, copying or the taking of any action in reliance on the
>>> contents of this information is strictly prohibited. If you have
>>> received this email in error, please immediately notify the sender via
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>>>
>> --
>> Douglas N. Greve, Ph.D.
>> MGH-NMR Center
>> gr...@nmr.mgh.harvard.edu
>> Phone Number: 617-724-2358
>> Fax: 617-726-7422
>>
>> Bugs: surfer.nmr.mgh.harvard.edu/fswiki/BugReporting
>> FileDrop: https://gate.nmr.mgh.harvard.edu/filedrop2
>> www.nmr.mgh.harvard.edu/facility/filedrop/index.html
>> Outgoing: ftp://surfer.nmr.mgh.harvard.edu/transfer/outgoing/flat/greve/
>>
>> _______________________________________________
>> Freesurfer mailing list
>> Freesurfer@nmr.mgh.harvard.edu
>> https://mail.nmr.mgh.harvard.edu/mailman/listinfo/freesurfer
>
>
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> https://mail.nmr.mgh.harvard.edu/mailman/listinfo/freesurfer
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>
> ________________________________
> The materials in this message are private and may contain Protected 
> Healthcare Information or other information of a sensitive nature. If you are 
> not the intended recipient, be advised that any unauthorized use, disclosure, 
> copying or the taking of any action in reliance on the contents of this 
> information is strictly prohibited. If you have received this email in error, 
> please immediately notify the sender via telephone or return mail.
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