Dear Richard Perry

Very much thanks for your comments that helped me to structure some thoughts. 
Would you mind if I further insist on some points. I will try to clarify a bit 
my vocabulary ;-)


>
> >This is why I was asking you whether EC (effective connectivity) should be
> >reserve for area that respond to 2 contrasts : the interaction, and the
> >covariation with the influencing area (A) = possibility 1? If true,
> >shouldn't
> > we mask the PPI result with the 'functional connectivity' result
> >(covariation
> >with area A) ?
>
> I may not have understood this question correctly.  When you say
> 'interaction' do you mean the PPI?

Yes (sorry not to be clearer)

> Or the ordinary interaction between two
> psychological factors in a factorial design.   I think that what you are
> suggesting is that if one could demonstrate that area B shows up in the PPI
> with area A (demonstrating 'effective connectivity'), the interpretation of
> this will depend on whether there is also a task-dependent increase in the
> CORRELATION (i.e. not just a change in slope) of activity in A and B
> ('functional connectivity').  However, if two areas have a neuromodulatory
> connection (particularly with a short time-course), this will still tend to
> lead to an increase in correlation in the BOLD signal, and I don't think
> that this can really be used to exclude a purely neuromodulatory
> connection.  However, I think that it is of interest to supplement the
> demonstration of a PPI with a demonstration of increased correlation
> between the signals in the two areas concerned if this is possible.
> However, an increased correlation on its own by no means implies a
> connection of any kind.  It could just be that the two areas both respond
> to the same aspect of the stimulus (or two correlated aspects of the
> stimulus).

Sure this is not a definitive argument, but considering the 'Okam knife' 
principle, one could suggest that correlation + PPI would be more simply 
explained by a change in effective connectivity (in the meaning of efficiency) 
from A to B. Would you reject that as a reviewer (keeping this very 
hypothetical formulation) ?


>
> >In the same way, should the modulatory connection (MC) = possibility 2,
> >only be
> >raised when the PPI activated area is also activated by the psychological
> >factor (and again mask by it) ?
>
> I don't agree with this.  The main effect of the psychological factor is
> modelled out as an effect of no interest in PPI studies.  With this gone,
> it is still perfectly possible to imagine variance in area A explaining
> more of the variance in area B in a task-dependent way without any change
> in the overall activity in the task vs control conditions.  An
> over-simplistic example would be if area B receives two alternative inputs,
> one from area A (during test conditions) and the other from area B

C ?

> (during
> control conditions) with no net change in the activity in any of these
> three areas between conditions.  This scenario is possible whether the
> connection is 'direct' or 'modulatory'.

Could you clarify why this symmetrical proposition (Activation by the psychol 
factor + PPI => stable modulatory effective connectivity as the simplest 
explanation) doesn't sounds as reasonable as the former one ? I may have missed 
something but, it seems that your argument could apply to both conditions.

>
> >At last, wouldn't the last possibility be raised when both factor in
> >isolation
> >do play a role in the PPI activated area (and then double masking the
> >interaction contrast with the two first) ?
> >Sure, a last possibility remain : that only the interaction term is
> >statistically significant. I suppose that in this case the interaction is
> >negative and is crossing around zero. And I cannot see how to decide from 
1,2
> >
> >or 3 (any idea is welcome).
>
> Sorry, you've lost me there.

Well it sounds as I will have to think about that a little bit more? ;-)


> >At last, since the region used as regressor is supposed to be related to a
> >factor orthogonal to the used contrast, how to be sure that the interaction
> >term does not simply reflect the interaction between the two factors
> >(unless it
> >has been computed, and thus all report of PPI should include the report of
> >this
> >computation as negative) ? In a way, the third area problem (area C that is
> >connected to A and B and explain why they are correlated), could be viewed
> >as
> >replaced by an other confounding factor.
>
> Sorry, I don't quite understand this question.  But in general there isn't
> necessarily a 'third area problem'.  An increase in the correlation of A
> and B because of a task-dependent input from area C need not show up as a
> psychophysiological interaction, which measures a change in regression
> slope, not a change in correlation.  A more specific third area problem is
> as described earlier.
>

Let me try to rephrase this more properly :
Say that A is correlated with the factor F1
Say that the PPI of A*F2 (a second factor) gives B.
The question is wouldn't we have to check that F2*F1 does not also fit B ?


>
> Sorry not to be more help!

It was much more that you seems to think. Very much thanks for your stimulating 
post.
Very best regards



Jack
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