Extracting ROI signals

Dear Professor,

I have a question about extracting ROI signals.

I think there are many pipelines for the step.

Extracting ROI signals after

1) (in Calcuate in Original Space) "Filtering" step

2) "Normalziation" step

3) "Smoothing" step

Are they all different results? 

I heard that, even if I get those signals after "Normalizatoin" or " Smoothing", the signals must be calcualted in the original space.

Do you think it is meaningful to compare those ROI signals from different steps?

Sincerely

Ido Ji