help > Mostly zero values when extracting connectivity strengths in the significant sub-network
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Dec 3, 2019  01:12 PM | laura_costello - National University of Ireland, Galway
Mostly zero values when extracting connectivity strengths in the significant sub-network
Hi Andrew,

I have a question regarding my design matrix set up and have mostly zero values when extracting connectivity strengths in the significant sub-network.

In a between-subjects design, I want to use an ANCOVA design to test the interaction between 2 bivariate variables; diagnosis (2 groups) and trauma (2 groups) co-varying for the effect of sex and age. An example of the design matrix I have used to test for this interaction between diagnosis and trauma is illustrated below. The contrast I used in NBS to test this interaction was set up as: structural connectivity matrices -weighted-by FA (.txt) "000100" F-test, 5000 permutations using extent. Do you think that this design matrix set up is correctly to test this interaction between diagnosis and trauma?

Columns: Intercept (1), Diagnosis (HC=1, SZ=-1), No Trauma (1)/Trauma (2), Interaction (1, -1, 2, -2), Sex (1, -1), Age

1 1 1 1 -1 45
1 1 2 2 -1 47
1 -1 1 -1 -1 44
1 -1 2 -2 -1 21
1 -1 1 -1 -1 34
1 -1 1 -1 -1 43

When I ran this F-test to test for an interaction effect, I obtained a sub-network at a threshold of 8.5. I then tried to extract the connectivity strengths between each connection in the sub-network using the matlab script previously recommended in the NBS forum and manual. However, the connectivity strength values that I obtain come out as '0' values in most cases. For reduced design using this same data set, I am able to extract connection strengths that appear reasonable for a F-test contrast investigating the main effect of diagnosis that is modelled as '0100'.

Below is an example of the output I receive in the matlab window after running the script to extract connection strengths for a sub-network relating to the interaction between diagnosis and trauma consisting of 26 edges, and 25 nodes in (T=8.5)
0
0.298
0
0
0
0
0
0
0
0.273
0
0
0
0
0
0
0
0
0
0.513
0
0

Do you know what might be causing these 0 values in the connectivity strengths to appear? Is it possible that there could be a limit to the extent of the statistical model/ design that is suitable for this approach? Would you have any suggestions how we might overcome the issue or indeed whether you think the sub-network is valid?

Thank you for your help in advance.
Kind Regards
Laura"
Dec 3, 2019  11:12 PM | Andrew Zalesky
RE: Mostly zero values when extracting connectivity strengths in the significant sub-network
Hi Laura,
thanks for reaching out.

First, I think that you probably want to model the main effect of trauma using 0 and 1, or -1 and 1. Using 1 and 2, will test for a parametric effect, rather than a difference between the trauma and no trauma group.

Note that you will also need to change the interaction column in the design matrix, if the main effect is changed as I suggest above.

Regarding the 0's in the extracted connection strengths, this is quite strange. Have you thresholded your connectivity matrices and do the connectivity matrices contain any zeros to begin with? I sense that something might have gone wrong when you have tried to extract the connection strengths after running the NBS.

I suggest making the change to the design matrix that I have described above and then trying to extract the connection strength again. If multiple 0's are still present, you are welcome to send me you NBS output and connection matrices. I can then have a closer look.

Andrew

Originally posted by laura_costello:
Hi Andrew,

I have a question regarding my design matrix set up and have mostly zero values when extracting connectivity strengths in the significant sub-network.

In a between-subjects design, I want to use an ANCOVA design to test the interaction between 2 bivariate variables; diagnosis (2 groups) and trauma (2 groups) co-varying for the effect of sex and age. An example of the design matrix I have used to test for this interaction between diagnosis and trauma is illustrated below. The contrast I used in NBS to test this interaction was set up as: structural connectivity matrices -weighted-by FA (.txt) "000100" F-test, 5000 permutations using extent. Do you think that this design matrix set up is correctly to test this interaction between diagnosis and trauma?

Columns: Intercept (1), Diagnosis (HC=1, SZ=-1), No Trauma (1)/Trauma (2), Interaction (1, -1, 2, -2), Sex (1, -1), Age

1 1 1 1 -1 45
1 1 2 2 -1 47
1 -1 1 -1 -1 44
1 -1 2 -2 -1 21
1 -1 1 -1 -1 34
1 -1 1 -1 -1 43

When I ran this F-test to test for an interaction effect, I obtained a sub-network at a threshold of 8.5. I then tried to extract the connectivity strengths between each connection in the sub-network using the matlab script previously recommended in the NBS forum and manual. However, the connectivity strength values that I obtain come out as '0' values in most cases. For reduced design using this same data set, I am able to extract connection strengths that appear reasonable for a F-test contrast investigating the main effect of diagnosis that is modelled as '0100'.

Below is an example of the output I receive in the matlab window after running the script to extract connection strengths for a sub-network relating to the interaction between diagnosis and trauma consisting of 26 edges, and 25 nodes in (T=8.5)
0
0.298
0
0
0
0
0
0
0
0.273
0
0
0
0
0
0
0
0
0
0.513
0
0

Do you know what might be causing these 0 values in the connectivity strengths to appear? Is it possible that there could be a limit to the extent of the statistical model/ design that is suitable for this approach? Would you have any suggestions how we might overcome the issue or indeed whether you think the sub-network is valid?

Thank you for your help in advance.
Kind Regards
Laura"
Dec 4, 2019  04:12 PM | laura_costello - National University of Ireland, Galway
RE: Mostly zero values when extracting connectivity strengths in the significant sub-network
Hi, Andrew

Thank you so much for your quick reply and suggestions. I have re-modelled No Trauma/Trauma as 1,-1 and similarly changed the interaction column in the design matrix to test this interaction (1,-1,1,-1) between trauma and diagnosis. I obtained an identical sub-network at T=8.5 as when the interaction was modelled as 1,-1,2 -2 and unfortunately the connectivity strengths extracted for these connections in this sub-network remain mostly zeros.

To answer your question, the structural connectivity matrices are thresholded by a minimum FA value of 0.2, and our matrices do contain some zero values however the percentage of zeros present in these are not too far off from other datasets we previously analysed for which we were able to obtain connection strengths. Our pipeline involves combining 86 cortico-subcortical nodes (desikan-killianey atlas, freesurfer v6.0) and edges are derived from performing CSD tractography (lmax=4) on a 32 gradient diffusion-weighted images (1b0, b-value of 1000m/s^2)

I really appreciate that you would be willing to have a look at these connectivity matrices for us. I could transfer these to you separately.

Many Thanks,
Laura
Dec 4, 2019  11:12 PM | Andrew Zalesky
RE: Mostly zero values when extracting connectivity strengths in the significant sub-network
Hi Laura,


If you are comfortable doing so, I suggest sending through your connectivity matrices, design matrix and other data inputs. Please also send a screenshot of NBS GUI just before you run the analysis.

Also send the code that you are using to extract the connectivity strengths.

My email is: azalesky@unimelb.edu.au

Andrew



Originally posted by laura_costello:
Hi, Andrew

Thank you so much for your quick reply and suggestions. I have re-modelled No Trauma/Trauma as 1,-1 and similarly changed the interaction column in the design matrix to test this interaction (1,-1,1,-1) between trauma and diagnosis. I obtained an identical sub-network at T=8.5 as when the interaction was modelled as 1,-1,2 -2 and unfortunately the connectivity strengths extracted for these connections in this sub-network remain mostly zeros.

To answer your question, the structural connectivity matrices are thresholded by a minimum FA value of 0.2, and our matrices do contain some zero values however the percentage of zeros present in these are not too far off from other datasets we previously analysed for which we were able to obtain connection strengths. Our pipeline involves combining 86 cortico-subcortical nodes (desikan-killianey atlas, freesurfer v6.0) and edges are derived from performing CSD tractography (lmax=4) on a 32 gradient diffusion-weighted images (1b0, b-value of 1000m/s^2)

I really appreciate that you would be willing to have a look at these connectivity matrices for us. I could transfer these to you separately.

Many Thanks,
Laura