Dear FSL experts,

I am trying to investigate group differences in resting-state networks using Melodic and DualRegression (DR), but have encountered some difficulties that I have been unable to solve. In a nutshell, performing DR after Melodic turns out p < 0.05 (FWE-corrected) significant clusters located in white matter regions and outside the brain (along with some cluster inside hypothesised grey matter regions). I have understood that getting significant cluster outside of the component map in question is not a problem, but finding these clusters in WM and outside of the brain worries me. I have re-run the analyses several times, changing some variables in the Melodic-stage, but always with the same kind of problems after DR.

My first guess was that registration to T1 (1mm, using BBR) and standard space (MNI-1mm or 2mm, with 12 DOF) had gone wrong. If I superimpose the melodic_IC.nii.gz file on the standard image, there are indeed some parts of the component maps that stretch into WM and outside the brain (respectively) – depending on how I threshold the melodic_IC.nii.gz file, of course. I have however used the transformation matrices from the registration phase to transform seed masks from standard and high-res space to fMRI-native space, and these transformations turn out OK. In Melodic, not including registration to T1 and changing the reference standard image does not help. I use the standard settings but usually extract 20 components and re-sample to 2mm. N = 30+22. In DR, there is not much to change in the settings themselves.

I cannot continue with my study until I have resolved this issue and have reliable results. What do you think could be the error here? Has anyone come across the same error and managed to solve it? I have found one way of alleviating the problem and that is to threshold the melodic_IC.nii.gz file (at some arbitrary level) before running DR on it. What do you think about this option?

Thank you very much for your help!

Regards,
Philip
PhD student, Karolinska Institutet