Dear PPI experts

I am hoping to get your help for the interpretation of gPPI results. Currently, I have a dataset with 4 conditions (within-subject). I have a very specific hypothesis on how a brain region (e.g., hippocampus) responses to these 4 conditions (monotonically increase from condition 1 to condition 4, namely control, low, medium, and high).

I ran a tradition activation-based analysis with a linear contrast for these 4 conditions and identified three major brain regions, namely mPFC, hippocampus, and angular gyrus, which followed this contrast. I then wanted to figure out whether the experimental conditions also modulated the communication across these different brain regions. Thus, I conducted a gPPI analysis. I got 4 interaction terms, and I conducted a linear contrast on the beta values of these 4 interaction terms.

I believe, the outcome of this contrast would tell me whether the connectivity between the seed region (e.g., hippocampus) and a target region also change as a linear function of my experimental manipulations. Surprisingly, I did not find any target regions that had shown up in the activation-based analysis, but found another region, the caudate, which had failed to reach the statistical threshold in the activation analysis, to positively correlated with the hippocampus. How should I interpret this PPI results in comparison to the activation results?

I learn from a tutorial that the PPI effect is independent of the typical effect (e.g., the contrast between conditions A and B). In other words, positive PPI effect has nothing to do with the sign of the contrast between conditions A and B. However, wouldn't we expect PPI analysis should also yield regions that show up in the activation-based analysis? If a certain brain region does not engage in a task to begin with (or at least fail to reach statistical significance based on some criteria, in this case the caudate), how could we justify the PPI finding of this region for a context-dependent correlation with the seed region (e.g., hippocampus)? Alternatively, since we have the taken into account all the original condition effects in our regression model for PPI analysis, could we just simply treat the PPI results as a completely independent analysis of the data to allow the detection of more subtle effect?

In sum, what the relationship between the PPI analysis and traditional activation analysis? Should one (PPI) contingent on the other (activation)? How to interpret their findings when they differ?

Thank you for your advice and clarification in advance!

Best regards,
Zane