= PPI Issues =
This document brings up some issues with PPI that the analysis guys and I are
concerned about. However, note that lots of papers using PPI have been
published, and there are always issues with every method, so you shouldn’t get
too bogged down with these worries. In fact, if you are the
bogging-down-in-worry type, better stop reading now.
== What exactly does PPI model? ==
A PPI effect is a task-specific change in correlation between areas, which
cannot be explained simply by a shared effect of task. What neural processes
could generate such a correlation?
One answer is probably unmodelled task related variance For example, say that
in the hypothetical maze-navigation experiment above, we have modelled
navigation using a block design (navigate/passive travel/rest modelled as
boxcars). What if PFC and HPC (independently) only really get involved in
navigation when you turn a corner? Then the true shape of the psychological
variable is rather more phasic than the boxcar we modelled, and thus there is
unmodelled task-related variance shared between the PFC and HPC which could be
driving both areas. This would lead to a spurious PPI.
A second type of unmodelled variance would be learning effects – for example
in a sequence-tapping task, performance might improve over the course of the
scanning session, and if this effect is not modelled, it could also drive a
spurious PPI.
Note that whilst the task model we have chosen is ‘partialled out’ of the
data, the unmodelled task variance is not – so in effect the less well our
model fits the data, the bigger the risk of a spurious PPI…
== PET approach vs. fMRI approach ==
A PPI approach has been used with PET in many papers (in fact, more than use
PPI with fMRI). In a PET experiment we only have one data point for each task
block. This leads to a subtle difference between PET-PPI and fMRI-PPI; in fMRI
PPI the ‘detailed’ time-course of activation (with on data point per TR) is
used and indeed in SPM a deconvolution algorithm is employed to make this
possible.
It seems to me that, if our data are modelled with a block design, then a
box-car-like PPI regressor could be used which disregards time-course
information on a scale faster than the block: after all, if we are proposing
that the brain processes of interest follow a box-car-like shape, interactions
of interest should also be box-car-like. I think using this approach would
improve the interpretability of PPI data, not least because a poor fit of the
boxcar shape cannot lead to a spurious PPI (as described above) in this case.
== Deconvolution ==
In order to generate a PPI regressor, we essentially find the product of the
task regressor and the time-course from the seed region. There is a problem
with this in that the time course of ‘activity’ in the seed region is actually
the time-course of the BOLD response and will therefore be shifted in time (by
the haemodynamic lag) with respect to the task regressor. One way to bring
these two into line is to convolve the task regressor, but not the
physiological time-course, with an HRF; this is the approach taken in
FSL. Another more complicated approach would be to try to deconvolve the
physiological time-course, to try to find the underlying neuronal time course,
and multiply this with the not-convolved task regressor; this is the approach
taken in SPM.
The reason for deconvolving is that the shape or lag of the HRF may be
different between brain regions, and if no deconvolution is applied, the PPI
analysis can be biased towards areas with a similar shaped/delayed
HRF. However, this is only really important for event-related designs; for
block designs the two methods are roughly equivalent.
A detailed discussion of the deconvolution issue is given in:
Gitelman DR, Penny WD, Ashburner J, Friston KJ (2003)<
>
Modeling regional and psychophysiologic interactions in fMRI: the importance of hemodynamic deconvolution.<
>
Neuroimage 19: 200-7.<
>
== When should you (not) use PPI? ==
In theory, PPI can be used with any experimental design. However, in practice
you are unlikely to see a significant effect in most (!) experimental
designs. The reason for this is that, to avoid the confounds described above,
you have to include the main effects from which you derived your interaction
variable in the GLM. But because the psychological, physiological and
interaction variables are now strongly correlated, the design lacks power. You
can see this from the covariance matrix below – we would need a signal change
of over 2% associated with the interaction term to see a significant effect.
{{attachment:Picture_8.png|power of PPI design}}
== Literature review of PPI ==
The PPI method was originally reported in 1997 in the following paper:
Friston, Buechel, Fink, Morris, Rolls and Dolan (1997)<
>
Psychophysiological and modulatory interactions in neuroimaging<
>
Neuroimage 6: 218-229<
>
… and has been implemented as a function in SPM since SPM2. A search in the
Science Citation Index revealed that of 189 papers citing the original Friston
paper, of which 40 were fMRI studies in which PPI had been used, of which 15
were published by people at the FIL and most of the rest had at least one
author at the FIL.
If these numbers really reflect the number of studies in which PPI has been
used ‘successfully’ (that is, in which there was a significant result), then
the number is surprisingly low, given that there is a PPI button in the SPM
GUI and given the number of posts about PPI on the SPM mailing list
(240). Further, about twice as many papers have been published using PPI with
PET as with fMRI. Applying some Bayesian inference based on the proportion of
PET to fMRI papers in the literature and the proportion of people likely to be
clicking the PPI button to those who got a paper out of it, I have to suspect
that this method does not work very successfully with fMRI data. This is
probably because of the orthogonality issue described above in non-factorial
designs.
== Factorial designs ==
PPI is supposed to work better with factorial designs. The reasons for this
are described in Friston (1997), which I quote here:
'''Factorial Designs (Friston et al, 1997)'''
''Psychophysiological interactions generally depend on factorial experimental designs, wherein one can introduce neurophysiological changes in one brain system that are uncorrelated with the stimulus or cognitive context one hopes to see an interaction with. We make this point explicit, suggesting that this is another example of the usefulness of factorial experiments: Although it is possible to test for psychophysiological interactions in almost any experimental design, the use of factorial designs ensures that any psychophysiological interactions will be detected with a fair degree of sensitivity. This is because the activities in the source area, the psychological context, and the interaction between them, will be roughly orthogonal and therefore one can use the first two as confounds with impunity. The converse situation, in which only one stimulus or cognitive factor has been changed, may render the activity in the source area and changes in the factor correlated. If this is the case, there is no guarantee that the interaction will be independent of either and its effect may be difficult to detect in the presence of the ‘‘main effects.’’''
This makes sense in some ways, but to me it seems strange – surely the only
reason this works is that you are including psychological variables which
differ from the contrast of interest, which would after all be the interaction
contrast 1, -1/3, -1/3, -1/3 ?
In other words, if we have a factorial design the psychological, physiological
and interaction regressors will be relatively orthogonal. Say we are doing an
experiment on memory in different sensory modalities, and we have a 2x2 design
with factors A vs. V (auditory and visual) and F vs. N (familiar vs. novel
stimuli). Then we might define a seed voxel for our PPI which is active in the
GLM contrast familiar-novel (perhaps in the medial temporal lobe), and analyse
the PPI in the visual condition (perhaps we think visual cortex will show a
stronger functional connection with medial temporal lobe in the familiar
condition). Then our regressors will be as follows:
* PSY: task contrast visual-auditory (shown in black below)
* PHYS: time-course from our voxel in medial temporal lobe– this is more active in the familiar condition than the novel condition (shown in blue below)
* PPI: the product of PSY and PHYS.
Because the contrast we used to select the seed region is not the same as the
contrast we are interested in in the PPI analysis, our regressors are now
looking a lot more orthogonal see Figure below).
{{attachment:Picture_9.png|factorial PPI}}