Hi Anderson,

If we want to estimate the interaction between modalities, should we transfer to joint inference (NPC or MANOVA/MANCOVA)? Just like FSLNets, explore the correlation between 2 RSN, using PALM to search the correlation between 2 modalities, for example, change of modality A causing positive/negative alteration of modality B?

Yes, this is possible through the use of voxelwise EVs. This example, on whether modality A is associated/correlated with modality B, can be done using A as input (dependent variable, -i), and B as a voxelwise EV in the design (or vice-versa). It can be done in either PALM or randomise.

1. For voxelwise EVs, do you mean using all_FA_skeletonised.nii/ GM_mod_merg_s3.nii / dr_stage2_ic[#ICA].nii as voxelwise EV for each modality?

2. If we add the voxelwise EVs via voxel-dependent EVs option from GLM GUI, do we still have to use the -evperdat <file> [evpos] [desnum] option for PALM/ --vxl and --vxf options for randomise? Or not necessary, only alternative?

And estimating the contribution of modality A and modality C to the alteration of modality B?

Yes, also possible. For this, use B as input, and prepare two designs, one having A as voxelwise EV, another with C as voxelwise EV, then run these two designs in PALM with -corrcon, and at the end, use fslmaths to find the largest corrected p-value across both, which will indicate a conjunction(IUT in the paper ).

Alternatively, for a joint test (UIT), use -npccon, that will do NPC over the contrasts for these two designs.

3. I know using

fslstats <input> -R

to get the largest corrected p-value, for fslmaths, do you mean

fslmaths <input> -Tmax

to calculate the largest corrected p-value for every contrast separately?

4. Further, can we calculate the weight/ percentage of contribution/ strength of modality A/ modality C to the change of modality C separately?

Moreover, can we use palm to find similar or same changed brain area during modalities, and the link between them: Modality A shows change in area A (near area B)/ area B, modality B shows change in area B, estimating whether the similar/same change (in spite of the indices for each modality are different) own some relationship.

Yes, this seems a case for NPC over modalities (-npcmod). Can be done in PALM, and works regardless of modalities being different (e.g., VBM and resting FMRI). However, they must be in the same space and have the same resolution.

5. How to find the similar or same changed brain area between modalities after NPC over modalities (-npcmod)? Manually visualize or by other way?

6. And how to check whether these similar/ same spatial change happen by chance, or there are some relationship between them, I mean, change in area A( near area B)/ area B for modality A affect the alteration of area B of modality B (or vice-versa).

7. You mentioned that "with modalities that focus on GM (VBM) and WM (FA), the overlap is minimal, and there won't be much left to analyse.". Our goal is to find similar/ same changed area between VBM and resting FMRI(as mentioned above), change for TBSS is close to chage for VBM or resting FMRI ( WM region A is close to GM region B), and check whether: a) Change of GM region A/ B for VBM affect change of GM region B of resting FMRI (or vice-versa); b) Change of WM region A for TBSS affect change of GM region B of VBM or resting FMRI (or vice-versa). Is possible for that? Sorry for my prolixity.

8. From the Masks and Voxelwise Regressors instruction, for NPC and MV, it's impossible to set mask by hand, PALM will create a mask across internally, is my understanding right?

Thanks.

Best regards,

Jian