Correcting your naughty insula: modelling respiration, pulse, and motion artifacts in fMRI

by Neuroconscience

important update: Thanks to commenter “DS”, I discovered that my respiration-related data was strongly contaminated due to mechanical error. The belt we used is very susceptible to becoming uncalibrated, if the subject moves or breathes very deeply for example. When looking at the raw timecourse of respiration I could see that many subjects, included the one displayed here, show a great deal of “clipping” in the timeseries. For the final analysis I will not use the respiration regressors, but rather just the pulse and motion. Thanks DS!

As I’m working my way through my latest fMRI analysis, I thought it might be fun to share a little bit of that here. Right now i’m coding up a batch pipeline for data from my Varela-award project, in which we compared “adept” meditation practitioners with motivation, IQ, age, and gender-matched controls on a response-inhibition and error monitoring task. One thing that came up in the project proposal meeting was a worry that, since meditation practitioners spend so much time working with the breath, they might respirate differently either at rest or during the task. As I’ve written about before, respiration and other related physiological variables such as cardiac-pulsation induced motion can seriously impact your fMRI results (when your heart beats, the veins in your brain pulsate, creating slight but consistent and troublesome MR artifacts). As you might expect, these artifacts tend to be worse around the main draining veins of the brain, several of which cluster around the frontoinsular and medial-prefrontal/anterior cingulate cortices. As these regions are important for response-inhibition and are frequently reported in the meditation literature (without physiological controls), we wanted to try to control for these variables in our study.

disclaimer: i’m still learning about noise modelling, so apologies if I mess up the theory/explanation of the techniques used! I’ve left things a bit vague for that reason. See bottom of article for references for further reading. To encourage myself to post more of these “open-lab notes” posts, I’ve kept the style here very informal, so apologies for typos or snafus. :D

To measure these signals, we used the respiration belt and pulse monitor that come standard with most modern MRI machines. The belt is just a little elastic hose that you strap around the chest wall of the subject, where it can record expansions and contractions of the chest to give a time series corresponding to respiration, and the pulse monitor a standard finger clip. Although I am not an expert on physiological noise modelling, I will do my best to explain the basic effects you want to model out of your data. These “non-white” noise signals include pulsation and respiration-induced motion (when you breath, you tend to nod your head just slightly along the z-axis), typical motion artifacts, and variability of pulsation and respiration. To do this I fed my physiological parameters into an in-house function written by Torben Lund, which incorporates a RETROICOR transformation of the pulsation and respiration timeseries. We don’t just use the raw timeseries due to signal aliasing- the phsyio data needs to be shifted to make each physiological event correspond to a TR. The function also calculates the respiratory volume time delay (RVT), a measure developed by Rasmus Birn, to model the variability in physiological parameters1. Variability in respiration and pulse volume (if one group of subjects tend to inhale sharply for some conditions but not others, for example) is more likely to drive BOLD artifacts than absolute respiratory volume or frequency (if one group of subjects tend to inhale sharply for some conditions but not others, for example). Finally, as is standard, I included the realignment parameters to model subject motion-related artifacts. Here is a shot of my monster design matrix for one subject:

DM_NVR

You can see that the first 7 columns model my conditions (correct stops, unaware errors, aware errors, false alarms, and some self-report ratings), the next 20 model the RETROICOR transformed pulse and respiration timeseries, 41 columns for RVT, 6 for realignment pars, and finally my session offsets and constant. It’s a big DM, but since we have over 1000 degrees of freedom, i’m not too worried about all the extra regressors in terms of loss of power. What would be worrisome is if for example stop activity correlated strongly with any of the nuisance variables –  we can see from the orthogonality plot that in this subject at least, that is not the case. Now lets see if we actually have anything interesting left over after we remove all that noise:

stop SPM

We can see that the Stop-related activity seems pretty reasonable, clustering around the motor and premotor cortex, bilateral insula, and DLPFC, all canonical motor inhibition regions (FWE-cluster corrected p = 0.05). This is a good sign! Now what about all those physiological regressors? Are they doing anything of value, or just sucking up our power? Here is the f-contrast over the pulse regressors:

pulse

Here we can see that the peak signal is wrapped right around the pons/upper brainstem. This makes a lot of sense- the area is full of the primary vasculature that ferries blood into and out of the brain. If I was particularly interested in getting signal from the brainstem in this project, I could use a respiration x pulse interaction regressor to better model this6. Penny et al find similar results to our cardiac F-test when comparing AR(1) with higher order AR models [7]. But since we’re really only interested in higher cortical areas, the pulse regressor should be sufficient. We can also see quite a bit of variance explained around the bilateral insula and rostral anterior cingulate. Interestingly, our stop-related activity still contained plenty of significant insula response, so we can feel better that some but not all of the signal from that region is actually functionally relevant. What about respiration?

resp

Here we see a ton of variance explained around the occipital lobe. This makes good sense- we tend to just slightly nod our head back and forth along the z-axis as we breath. What we are seeing is the motion-induced artifact of that rotation, which is most severe along the back of the head and periphery of the brain. We see a similar result for the overall motion regressors, but flipped to the front:

Ignore the above, respiration regressor is not viable due to “clipping”, see note at top of post. Glad I warned everyone that this post was “in progress” :) Respiration should be a bit more global, restricted to ventricles and blood vessels.

motion

Wow, look at all the significant activity! Someone call up Nature and let them know, motion lights up the whole brain! As we would expect, the motion regressor explains a ton of uninteresting variance, particularly around the prefrontal cortex and periphery.

I still have a ways to go on this project- obviously this is just a single subject, and the results could vary wildly. But I do think even at this point we can start to see that it is quite easy and desirable to model these effects in your data (Note: we had some technical failure due to the respiration belt being a POS…) I should note that in SPM, these sources of “non-white” noise are typically modeled using an autoregressive (AR(1)) model, which is enabled in the default settings (we’ve turned it off here). However as there is evidence that this model performs poorly at faster TRs (which are the norm now), and that a noise-modelling approach can greatly improve SnR while removing artifacts, we are likely to get better performance out of a nuisance regression technique as demonstrated here [4]. The next step will be to take these regressors to a second level analysis, to examine if the meditation group has significantly more BOLD variance-explained by physiological noise than do controls. Afterwards, I will re-run the analysis without any physio parameters, to compare the results of both.

References:


1. Birn RM, Diamond JB, Smith MA, Bandettini PA.
Separating respiratory-variation-related fluctuations from neuronal-activity-related fluctuations in fMRI.
Neuroimage. 2006 Jul 15;31(4):1536-48. Epub 2006 Apr 24.

2. Brooks J.C.W., Beckmann C.F., Miller K.L. , Wise R.G., Porro C.A., Tracey I., Jenkinson M.
Physiological noise modelling for spinal functional magnetic resonance imaging studies
NeuroImage in press: DOI: doi: 10.1016/j.neuroimage.2007.09.018

3. Glover GH, Li TQ, Ress D.
Image-based method for retrospective correction of physiological motion effects in fMRI: RETROICOR.
Magn Reson Med. 2000 Jul;44(1):162-7.

4. Lund TE, Madsen KH, Sidaros K, Luo WL, Nichols TE.
Non-white noise in fMRI: does modelling have an impact?
Neuroimage. 2006 Jan 1;29(1):54-66.

5. Wise RG, Ide K, Poulin MJ, Tracey I.
Resting fluctuations in arterial carbon dioxide induce significant low frequency variations in BOLD signal.
Neuroimage. 2004 Apr;21(4):1652-64.

2. Brooks J.C.W., Beckmann C.F., Miller K.L. , Wise R.G., Porro C.A., Tracey I., Jenkinson M.
Physiological noise modelling for spinal functional magnetic resonance imaging studies
NeuroImage in press: DOI: doi: 10.1016/j.neuroimage.2007.09.018

7. Penny, W., Kiebel, S., & Friston, K. (2003). Variational Bayesian inference for fMRI time series. NeuroImage, 19(3), 727–741. doi:10.1016/S1053-8119(03)00071-5