Hi Everyone,

Thank you all for your very helpful feedback. So, just to summarize on the
consensus, and please correct me if I am wrong:

ICA+FIX denoising presumably already removes the WM and CSF related
variance from the signal, in a non-aggressive way (which is one benefit of
the FIXed data) - meaning it only removes variance that is unique to the
WM/CSF and not that which is shared with the signal.

Additional WM and CSF regression isnt necessary. One problem is that WM/CSF
aren't clean regressors, so if we were to regress these out we would be
"too aggressive", meaning remove too much from the signal.

Physiological noise regression may make for cleaner data, however this
hasn't been formally implemented yet in HCP, and also need to be careful of
not removing it too "aggressively" (ie removing too much variance that
physio data has in common with the signal), in addition to the issue of
combining the physio regressor with the other regressors.

I think that's the jist. Thanks again, was helpful to get everyone's input.
Joelle

On Thu, Dec 10, 2015 at 5:45 AM, Glasser, Matthew <glass...@wustl.edu>
wrote:

> 1) My point was that it isn’t the same because of the aggressive vs non
> aggressive difference.  I wasn’t making an argument for using WM and CSF
> instead of ICA+FIX or in addition to it.  It doesn’t really add anything
> because WM and CSF don’t contain clean regressors of any noise signal.
>
> 3) I was assuming you had made them orthogonal by regressing A out of both
> the data and B and then regressing residual B out of the data.  If you do
> that, it wasn’t clear that a single model is necessary, though it might be
> desirable for simplicity.
>
> Matt.
>
> From: Stephen Smith <st...@fmrib.ox.ac.uk>
> Date: Thursday, December 10, 2015 at 3:43 AM
> To: Maarten Mennes <mennes.maar...@gmail.com>
> Cc: Matt Glasser <glass...@wustl.edu>, Greg Burgess <gcburg...@gmail.com>,
> "hcp-users@humanconnectome.org" <hcp-users@humanconnectome.org>
> Subject: Re: [HCP-Users] FIX-denoised
>
> Hi all
>
> I think Greg was making the valid point that:  if you want to regress the
> full space of A and B out of your data, it is not correct to regress out A
> and then afterwards regress out B, unless A and B are orthogonal.  To do it
> correctly you either need to combine [A B] into a single model to regress
> out of the data, or else regress A out of the data and also out of B, and
> then regress the new B out of the data.
>
> Hope that helps,
> Steve.
>
>
> On 10 Dec 2015, at 08:46, Maarten Mennes <mennes.maar...@gmail.com> wrote:
>
> Hi Matt,
>
> I'm not sure I follow your reasoning under 1). I would prefer a much
> richer 'signal vs. noise' model as provided by ICA+FIX compared to
> aggressive regression of (potentially GM contaminated) WM and CSF signal.
> This is also what you indicate at the end of your answer: regressing out WM
> and CSF after ICA+FIX doesn't seem to make much of a difference.
>
> With 3) I believe Greg is pointing to combining all regressors into one
> model, ie. doing non-aggressive motion, WM, and CSF regression, by adding
> those regressors to the ICA+FIX generated model. There I again don't see
> what the benefit would be of adding very crude WM/CSF regressors over the
> more fine-grained ones ICA+FIX is providing. But it seems you are working
> on a manuscript that addresses some of these points. Looking forward to
> that then!
>
> Cheers,
> Maarten
>
>
>
> On Thu, Dec 10, 2015 at 3:39 AM, Glasser, Matthew <glass...@wustl.edu>
> wrote:
>
>> 1) Greg I covered this in my comments on your manuscript.  For the benefit
>> of others: it is not the case that ICA+FIX would replace using WM and CSF
>> timecourses.  The reason is that ICA+FIX regresses noise components out of
>> the data in a ³non aggressive² approach (computing betas for all
>> components and then subtracting only the data explained by the noise
>> components).  This is different from how the movement parameters are
>> removed (where all of the variance explained by those timeseries is
>> aggressively regressed out).  If you aggressively regress out WM and CSF
>> timecourses, this will remove all variance explained by them, even that
>> which is shared by the signal components and would not be removed in
>> ICA+FIX.  It is important that your WM and CSF regressors are kept well
>> away from the grey matter, as you do not want to be doing GSR ³light² (or
>> any GSR/MGTR for that matter).  I have investigated whether removing WM or
>> CSF regressors is helpful.  For WM, it really doesn¹t make much of a
>> difference unless there are MR acquisition artifacts (e.g. some receive
>> coil elements stopped working during the scan).  One of the reasons we
>> know there aren¹t global movement related effects being left in the HCP
>> data is that regressing WM out doesn¹t do much (if there were, one would
>> expect them to be picked up by the WM timeseries).  CSF may be more
>> correlated with physiological noise, but it isn¹t a very clean regressor
>> for this (nor is WM).
>>
>> 2) Indeed there does appear to be global grey matter physiological noise
>> which we need to separate from global neural signal.  We are working on
>> ways to do this (it is likely that we will want to investigate both
>> external approaches like regressing physiological regressors out and
>> internal approaches that attempt to separate physiological noise from the
>> data itself).  It would certainly be helpful if the HCP¹s physiological
>> noise regressors were preprocessed for heart rate and respiratory end
>> tidal volume traces and those regressors were released publicly.
>>
>> 3) I don¹t understand this.
>>
>> Peace,
>>
>> Matt.
>>
>> On 12/9/15, 5:39 PM, "hcp-users-boun...@humanconnectome.org on behalf of
>> Greg Burgess" <hcp-users-boun...@humanconnectome.org on behalf of
>> gcburg...@gmail.com> wrote:
>>
>> >Just a few comments:
>> >
>> >1) I agree with Maarten that FIX-denoising is effectively removing WM and
>> >CSF components from the FIX timeseries data. My understanding is that
>> >Matt Glasser has evaluated the incremental benefit for regressing the
>> >(average) WM and CSF timeseries and concluded that there is no additional
>> >benefit after FIX. I don¹t believe that anyone has tested whether
>> >additional WM and CSF components (such as implemented in CompCor) can
>> >remove noise variance above and beyond FIX, though, in theory, FIX should
>> >capture those as well.
>> >
>> >2) Some analyses that I have conducted suggest that FIX denoising may
>> >leave behind some proportion of physiological noise, especially that
>> >which is more globally-distributed across gray matter. I am hoping to
>> >investigate whether physiological regressors can remove that additional
>> >proportion.
>> >
>> >3) It is probably important to regress physiological regressors, motion
>> >regressors, and FIX noise regressors simultaneously from the timeseries.
>> >Otherwise, the fit of some regressors to the timeseries will be worsened
>> >by removing the other regressors from the timeseries. It might work to
>> >regress motion and noise ICs from the physio regressors, and then regress
>> >physio from the FIX timeseries, but I am not certain that it will (e.g.,
>> >for RETROICOR-type regressors).
>> >
>> >4) If you decide to investigate physiological regressors, please use
>> >those release in the 900 subject packages, because the physiological
>> >measures in the 500 subject release had a timing bug. There will be
>> >additional information about the updated physiological measures coming in
>> >the near future.
>> >
>> >--Greg
>> >
>> >____________________________________________________________________
>> >Greg Burgess, Ph.D.
>> >Staff Scientist, Human Connectome Project
>> >Washington University School of Medicine
>> >Department of Neuroscience
>> >Phone: 314-362-7864
>> >Email: gburg...@wustl.edu
>> >
>> >> On Dec 9, 2015, at 4:40 PM, Maarten Mennes <mennes.maar...@gmail.com>
>> >>wrote:
>> >>
>> >> One could also argue that WM and CSF regression is not needed anymore
>> >>if the FIX denoising worked as intended... Given that FIX will look for
>> >>components that correlate with WM and CSF signal these signals are
>> >>already regressed out if components were properly identified. The same
>> >>is true for the physiological data.
>> >>
>> >> Note that this is different from a tool like ICA-AROMA which is not
>> >>trained to identify WM/CSF/physiological components, in this case extra
>> >>nuisance regression might effectively come in handy. But I don't see
>> >>this need in FIX-denoised data.
>> >>
>> >> Or am I missing something obvious?
>> >>
>> >> Cheers,
>> >> Maarten
>> >>
>> >>
>> >> On Wed, Dec 9, 2015 at 11:10 PM, Harms, Michael <mha...@wustl.edu>
>> >>wrote:
>> >>
>> >> See inline below.
>> >>
>> >> --
>> >> 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: Joelle Zimmermann <joelle.t.zimmerm...@gmail.com>
>> >> Date: Wednesday, December 9, 2015 3:08 PM
>> >> To: "Harms, Michael" <mha...@wustl.edu>
>> >> Cc: "hcp-users@humanconnectome.org" <hcp-users@humanconnectome.org>
>> >> Subject: Re: [HCP-Users] FIX-denoised
>> >>
>> >> Hi Michael,
>> >>
>> >> Thanks for your help. I have a few more questions below..
>> >>
>> >> Has an average timeseries for WM (and CSF) signal been already computed
>> >>by HCP?
>> >> Perhaps this is the "rfMRI_REST1_LR_WM.txt" and the
>> >>"rfMRI_REST1_LR_CSF.txt" in the FIX extended package?
>> >> Yes, you could use those.  See the scripts in the RestingStateStats
>> >>folder in github if you want to know the details of how exactly those
>> >>were derived.  But see next for some downstream files that you could use
>> >>instead that would save you a lot of methodological preparation.
>> >>
>> >> Is there a recommended way of regressing these out?
>> >> Take a look at the RestingStateStats/RestingStateStats.m code.  In
>> >>particular, if starting from the "MPP" WM and CSF time courses (i.e.,
>> >>from the non-cleaned data) you need to apply the same HP filter, and
>> >>regress out the motion parameters and the FIX-identified noise
>> >>components, so that you don¹t re-introduce noise related to those
>> >>operations into the cleaned data.  And if you were to regress out WM and
>> >>CSF sequentially, then you need to do something similar to account for
>> >>the order there as well.  It gets a bit complicated.  :)
>> >>
>> >> Fortunately, looking at the RestingStateStats.m script, there should be
>> >>files "*_Cleaned{WM,CSF}tc.txt" that have already done all that for you.
>> >> In which case, all you need to do is use those simultaneously in a
>> >>regression to remove the noise space spanned by those two already
>> >>supplied "*_Cleaned{WM,CSF}tc.txt" files from the hp2000_clean.nii.gz
>> >>volume data or hp2000_clean.dtseries.nii CIFTI data. (See e.g., Lines
>> >>330-334 in RestingStateStats.m for what I mean by using them in a
>> >>"simultaneous" regression).
>> >>
>> >> I think I have that right, but Matt wrote that particular bit of code,
>> >>so hopefully he will correct if I've misstated anything.
>> >>
>> >>  Related to my previous question: Has physiological data
>> >>(³rfMRI_REST1_LR_Physio_log²) already been regressed from the FIX
>> >>denoised data?
>> >> I cannot actually find a rfMRI Physio log file in the FIX-ed dataset, I
>> >>can only find this Physio log file in the minimally preprocessed
>> >>dataset. I suppose I can use that one? But I'd assume there should be
>> >>one in the FIX-ed dataset folder as well...
>> >> We haven't yet extended the RestingStateStats.m code to incorporate
>> >>regressors derived from the physio files, which is why the physio time
>> >>series isn't also part of the FIX-extended packages.  If you want to try
>> >>regressing out physio as well, again make sure that you first regress
>> >>out of any physio regressors all the preceding filtering/regression
>> >>steps, so that you don't re-introduce any previously removed noise from
>> >>the cleaned data.
>> >>
>> >>
>> >> Thanks,
>> >> Joelle
>> >>
>> >> On Wed, Dec 9, 2015 at 2:43 PM, Harms, Michael <mha...@wustl.edu>
>> wrote:
>> >>
>> >> Hi,
>> >> See inline below.
>> >>
>> >> --
>> >> 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: Joelle Zimmermann <joelle.t.zimmerm...@gmail.com>
>> >> Date: Wednesday, December 9, 2015 1:26 PM
>> >> To: "hcp-users@humanconnectome.org" <hcp-users@humanconnectome.org>
>> >> Subject: [HCP-Users] FIX-denoised
>> >>
>> >> Hi everyone,
>> >>
>> >> I'm interested in using the FIX-denoised data, and am currently looking
>> >>at the extended package, as I'm interested in the volumetric data.
>> >>
>> >> I'm wondering whether the motion parameters have already been regressed
>> >>out from the FIX denoised rfMRI_REST1_LR_hp2000_clean.nii.gz?
>> >> YES
>> >>
>> >> I'm assuming yes, that the FIX denoised actually already deals with
>> >>this by separating the motion-related noise into a component and
>> >>filtering that out of the signal?  I assume so based on the following
>> >>snippet from the manual describing FIX-ed data:
>> >> "As part of this cleanup, we also used 24 confound timeseries derived
>> >>from the motion estimation (the 6 rigid-body parameter timeseries, their
>> >>backwards-looking temporal derivatives, plus all 12 resulting regressors
>> >>squared ‹ Satterthwaite et al., 2013). The motion parameters have the
>> >>temporal highpass filtering applied to them and are then regressed out
>> >>of the data aggressively, as they are not expected to contain variance
>> >>of interest."
>> >> Am I correct?
>> >> YES
>> >>
>> >> Has white matter and/or cerebrospinal fluid been regressed already from
>> >>the FIX denoised fMRI timeseries?
>> >> NO
>> >>
>> >> Has physiological data (³rfMRI_REST1_LR_Physio_log²) already been
>> >>regressed from the FIX denoised data?
>> >> NO
>> >>
>> >> Any pointers would be much appreciated.
>> >>
>> >> Thanks,
>> >> Joelle
>> >>
>> >>
>> >>
>> >>
>> >>
>> >>
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>> >> --
>> >> Maarten Mennes, Ph.D.
>> >> Senior Researcher
>> >> Donders Institute for Brain, Cognition and Behaviour
>> >> Radboud University Nijmegen
>> >> Nijmegen
>> >> The Netherlands
>> >>
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> --
> Maarten Mennes, Ph.D.
> Senior Researcher
> Donders Institute for Brain, Cognition and Behaviour
> Radboud University Nijmegen
> Nijmegen
> The Netherlands
>
> Google Scholar Author Link
> <http://scholar.google.com/citations?user=pLlSTVgAAAAJ&hl=en>
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