Hi Doug et al,

The 2nd question is something I've wondered about. Doesn't a Bonferroni correction assume that the measures are independent? If so, I think in the case of subcortical structures, it is incorrect to use this method, as e.g. the putamen and pallidal volumes are not independent of one another. If not, and it is acceptable to use when there are dependencies between measures, how do you calculate the FWE? It wouldn't be equal to alpha/n, unless I am misunderstanding something.

Thanks, Chris ________________________________________ From: freesurfer-bounces@nmr.mgh.harvard.edu [freesurfer-bounces@nmr.mgh.harvard.edu] on behalf of Douglas N Greve [greve@nmr.mgh.harvard.edu] Sent: Friday, July 20, 2012 2:38 PM To: freesurfer@nmr.mgh.harvard.edu Subject: Re: [Freesurfer] Questions about correction over 2 hemispheres and MCC

Hi Reem, it looks like you've done everything correctly (sorry for the null result). As for your second, question, I don't think there is a way other than Bonferroni. You can try FDR, but it makes the interpretation a little messy. doug

On 07/19/2012 07:59 PM, Reem Jan wrote:

Hi Doug

I hope it’s okay that I double check I’m doing the correction over 2 hemispheres correctly and ask a question regarding correction for multiple comparisons. I will briefly describe what I have done:

I have 2 groups of subjects – Drug addicts (n= 17) and controls (n=20).

1.I ran a surface thickness study:

·For the ‘mri_glmfit’ command, I used DOSS and specified a contrast of +1 -1 0 (Controls > MA)

·I ran a pre-cached simulation with the following command: mri_glmfit-sim --glmdir lh.group_age.glmdir --cache 4 pos

·This simulation should only have corrected for the left hemisphere as I understand it. My cluster summary text file showed me that a cluster survived in the insula. I interpreted this as ‘controls had higher grey matter thickness in this cluster located in the insula than drug addicts’. However, this was only corrected over the left hemisphere (when I ran the same simulation in the right hemisphere, nothing survived multiple comparison correction).

·I now wanted to correct the lh results for 2 hemispheres. From the help menu of ‘mri_glmfit-sim’, I understood you can do this in 2 ways, are both of these correct and give the same result?

a.mri_glmfit-sim --glmdir lh.group_age.glmdir --cache 4 pos --2 spaces --no-sim csdbase

b.mri_glmfit-sim --glmdir lh.group_age.glmdir --cache 4 pos --cwpvalthresh 0.025

ØNo clusters survived the Bonferroni correction over both hemispheres. So I assume I can no longer report this result?

2.I ran a subcortical volume study:

·I used SPSS to perform the statistical analysis on each of 14 subcortical structures (left and right). Is there a good way to correct for multiple comparisons, apart from Bonferroni, which would be very conservative?

Many thanks for your advice.

Kind regards

Reem

*Reem Jan***

BPharm (Hons), RegPharmNZ

PhD Student / Pharmacist

School of Pharmacy, Faculty of Medical & Health Sciences, The University of Auckland, Private Bag 92019, Auckland, New Zealand.

Ph: +64 9 373 7599 ext 81138. DDI: +64 9 923 1138

F: +64 9 367 7192

*From:*freesurfer-bounces@nmr.mgh.harvard.edu [mailto:freesurfer-bounces@nmr.mgh.harvard.edu] *On Behalf Of *Douglas Greve *Sent:* Friday, 20 July 2012 11:52 a.m. *To:* freesurfer@nmr.mgh.harvard.edu *Subject:* Re: [Freesurfer] slice-by-slice predictors

Sorry, not possible.

On 7/19/12 6:56 PM, Caspar M. Schwiedrzik wrote:

Hi! Is it possible to have slice-by-slice predictors in Freesurfer, and if so, how? Thanks, Caspar

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The information in this e-mail is intended only for the person to whom it is addressed. If you believe this e-mail was sent to you in error and the e-mail contains patient information, please contact the Partners Compliance HelpLine at http://www.partners.org/complianceline . If the e-mail was sent to you in error but does not contain patient information, please contact the sender and properly dispose of the e-mail.

What about, for example, the correlations I've seen in a cohort of subjects.

In 158 subjects aged 10-19 (both controls and patients), the correlation between L & R thalamus is 0.91, and the correlations between L & R of caudate, putamen, pallidum, hippocampus, and amygdala were all 0.75 or higher.

I would think that a Bonferroni correction would be incredibly conservative and, in my opinion, just plain wrong because true significant diff's would be missed. Is there any principled way of dealing with multiple tests that are correlated?

Thanks, Chris ________________________________________ From: Bruce Fischl [fischl@nmr.mgh.harvard.edu] Sent: Saturday, July 21, 2012 12:01 PM To: Watson, Christopher Cc: Douglas N Greve; freesurfer@nmr.mgh.harvard.edu Subject: Re: [Freesurfer] Questions about correction over 2 hemispheres and MCC

Hi Chris,

bonferroni will be overly conservative in that case, but we rarely really know the true covariance structure of the data, so we would rather err on the side of being conservative.

cheers Bruce On Fri, 20 Jul 2012, Watson, Christopher wrote:

Hi Doug et al,

The 2nd question is something I've wondered about. Doesn't a Bonferroni correction assume that the measures are independent? If so, I think in the case of subcortical structures, it is incorrect to use this method, as e.g. the putamen and pallidal volumes are not independent of one another. If not, and it is acceptable to use when there are dependencies between measures, how do you calculate the FWE? It wouldn't be equal to alpha/n, unless I am misunderstanding something.

Thanks, Chris ________________________________________ From: freesurfer-bounces@nmr.mgh.harvard.edu [freesurfer-bounces@nmr.mgh.harvard.edu] on behalf of Douglas N Greve [greve@nmr.mgh.harvard.edu] Sent: Friday, July 20, 2012 2:38 PM To: freesurfer@nmr.mgh.harvard.edu Subject: Re: [Freesurfer] Questions about correction over 2 hemispheres and MCC

Hi Reem, it looks like you've done everything correctly (sorry for the null result). As for your second, question, I don't think there is a way other than Bonferroni. You can try FDR, but it makes the interpretation a little messy. doug

On 07/19/2012 07:59 PM, Reem Jan wrote:

...

Hi Doug

I hope it?s okay that I double check I?m doing the correction over 2 hemispheres correctly and ask a question regarding correction for multiple comparisons. I will briefly describe what I have done:

I have 2 groups of subjects ? Drug addicts (n= 17) and controls (n=20).

1.I ran a surface thickness study:

·For the ?mri_glmfit? command, I used DOSS and specified a contrast of +1 -1 0 (Controls > MA)

·I ran a pre-cached simulation with the following command: mri_glmfit-sim --glmdir lh.group_age.glmdir --cache 4 pos

·This simulation should only have corrected for the left hemisphere as I understand it. My cluster summary text file showed me that a cluster survived in the insula. I interpreted this as ?controls had higher grey matter thickness in this cluster located in the insula than drug addicts?. However, this was only corrected over the left hemisphere (when I ran the same simulation in the right hemisphere, nothing survived multiple comparison correction).

·I now wanted to correct the lh results for 2 hemispheres. From the help menu of ?mri_glmfit-sim?, I understood you can do this in 2 ways, are both of these correct and give the same result?

a.mri_glmfit-sim --glmdir lh.group_age.glmdir --cache 4 pos --2 spaces --no-sim csdbase

b.mri_glmfit-sim --glmdir lh.group_age.glmdir --cache 4 pos --cwpvalthresh 0.025

ØNo clusters survived the Bonferroni correction over both hemispheres. So I assume I can no longer report this result?

2.I ran a subcortical volume study:

·I used SPSS to perform the statistical analysis on each of 14 subcortical structures (left and right). Is there a good way to correct for multiple comparisons, apart from Bonferroni, which would be very conservative?

Many thanks for your advice.

Kind regards

Reem

*Reem Jan***

BPharm (Hons), RegPharmNZ

PhD Student / Pharmacist

School of Pharmacy, Faculty of Medical & Health Sciences, The University of Auckland, Private Bag 92019, Auckland, New Zealand.

Ph: +64 9 373 7599 ext 81138. DDI: +64 9 923 1138

F: +64 9 367 7192

*From:*freesurfer-bounces@nmr.mgh.harvard.edu [mailto:freesurfer-bounces@nmr.mgh.harvard.edu] *On Behalf Of *Douglas Greve *Sent:* Friday, 20 July 2012 11:52 a.m. *To:* freesurfer@nmr.mgh.harvard.edu *Subject:* Re: [Freesurfer] slice-by-slice predictors

Sorry, not possible.

On 7/19/12 6:56 PM, Caspar M. Schwiedrzik wrote:

Hi! Is it possible to have slice-by-slice predictors in Freesurfer, and if so, how? Thanks, Caspar

---

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Freesurfer mailing list Freesurfer@nmr.mgh.harvard.edu https://mail.nmr.mgh.harvard.edu/mailman/listinfo/freesurfer

-- Douglas N. Greve, Ph.D. MGH-NMR Center greve@nmr.mgh.harvard.edu Phone Number: 617-724-2358 Fax: 617-726-7422

Bugs: surfer.nmr.mgh.harvard.edu/fswiki/BugReporting FileDrop: www.nmr.mgh.harvard.edu/facility/filedrop/index.html

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The information in this e-mail is intended only for the person to whom it is addressed. If you believe this e-mail was sent to you in error and the e-mail contains patient information, please contact the Partners Compliance HelpLine at http://www.partners.org/complianceline . If the e-mail was sent to you in error but does not contain patient information, please contact the sender and properly dispose of the e-mail.

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Hi Bruce, Jürgen and Chris

Thank you for elaborating further. I've gone with a Bonferroni correction as I had a limited number of tests (a-priori hypothesis). But just out of interest Chris, you mentioned you found correlations between subcortical structures, do you have a reference I could look at? The tool that Jürgen suggested requires we enter a correlation coefficient, so I wondered if I could use published values or whether I'd need to calculate my own (if so, could you please recommend a way of doing that in Freesurfer or FSL?)

Many thanks in advance

Kind regards Reem

-----Original Message----- From: freesurfer-bounces@nmr.mgh.harvard.edu [mailto:freesurfer-bounces@nmr.mgh.harvard.edu] On Behalf Of Jürgen Hänggi Sent: Sunday, 22 July 2012 7:47 p.m. To: Watson, Christopher Cc: Freesurfer Mailinglist Subject: Re: [Freesurfer] Questions about correction over 2 hemispheres and MCC

Hi Chris

Yes there are such tools. Bonferroni oder Sidak test that take into account the correlated measures. Here you can find these tools

http://www.quantitativeskills.com/sisa/calculations/bonfer.htm

Cheers Jürgen

On [DATE], "Watson, Christopher" <[ADDRESS]> wrote:

What about, for example, the correlations I've seen in a cohort of subjects.

In 158 subjects aged 10-19 (both controls and patients), the correlation between L & R thalamus is 0.91, and the correlations between L & R of caudate, putamen, pallidum, hippocampus, and amygdala were all 0.75 or higher.

I would think that a Bonferroni correction would be incredibly conservative and, in my opinion, just plain wrong because true significant diff's would be missed. Is there any principled way of dealing with multiple tests that are correlated?

Thanks, Chris ________________________________________ From: Bruce Fischl [fischl@nmr.mgh.harvard.edu] Sent: Saturday, July 21, 2012 12:01 PM To: Watson, Christopher Cc: Douglas N Greve; freesurfer@nmr.mgh.harvard.edu Subject: Re: [Freesurfer] Questions about correction over 2 hemispheres and MCC

Hi Chris,

bonferroni will be overly conservative in that case, but we rarely really know the true covariance structure of the data, so we would rather err on the side of being conservative.

cheers Bruce On Fri, 20 Jul 2012, Watson, Christopher wrote:

...

Hi Doug et al,

The 2nd question is something I've wondered about. Doesn't a Bonferroni correction assume that the measures are independent? If so, I think in the case of subcortical structures, it is incorrect to use this method, as e.g. the putamen and pallidal volumes are not independent of one another. If not, and it is acceptable to use when there are dependencies between measures, how do you calculate the FWE? It wouldn't be equal to alpha/n, unless I am misunderstanding something.

Thanks, Chris ________________________________________ From: freesurfer-bounces@nmr.mgh.harvard.edu [freesurfer-bounces@nmr.mgh.harvard.edu] on behalf of Douglas N Greve [greve@nmr.mgh.harvard.edu] Sent: Friday, July 20, 2012 2:38 PM To: freesurfer@nmr.mgh.harvard.edu Subject: Re: [Freesurfer] Questions about correction over 2 hemispheres and MCC

Hi Reem, it looks like you've done everything correctly (sorry for the null result). As for your second, question, I don't think there is a way other than Bonferroni. You can try FDR, but it makes the interpretation a little messy. doug

On 07/19/2012 07:59 PM, Reem Jan wrote:

...

Hi Doug

I hope it?s okay that I double check I?m doing the correction over 2 hemispheres correctly and ask a question regarding correction for multiple comparisons. I will briefly describe what I have done:

I have 2 groups of subjects ? Drug addicts (n= 17) and controls (n=20).

1.I ran a surface thickness study:

·For the ?mri_glmfit? command, I used DOSS and specified a contrast of +1 -1 0 (Controls > MA)

·I ran a pre-cached simulation with the following command: mri_glmfit-sim --glmdir lh.group_age.glmdir --cache 4 pos

·This simulation should only have corrected for the left hemisphere as I understand it. My cluster summary text file showed me that a cluster survived in the insula. I interpreted this as ?controls had higher grey matter thickness in this cluster located in the insula than drug addicts?. However, this was only corrected over the left hemisphere (when I ran the same simulation in the right hemisphere, nothing survived multiple comparison correction).

·I now wanted to correct the lh results for 2 hemispheres. From the help menu of ?mri_glmfit-sim?, I understood you can do this in 2 ways, are both of these correct and give the same result?

a.mri_glmfit-sim --glmdir lh.group_age.glmdir --cache 4 pos --2 spaces --no-sim csdbase

b.mri_glmfit-sim --glmdir lh.group_age.glmdir --cache 4 pos --cwpvalthresh 0.025

ØNo clusters survived the Bonferroni correction over both hemispheres. So I assume I can no longer report this result?

2.I ran a subcortical volume study:

·I used SPSS to perform the statistical analysis on each of 14 subcortical structures (left and right). Is there a good way to correct for multiple comparisons, apart from Bonferroni, which would be very conservative?

Many thanks for your advice.

Kind regards

Reem

*Reem Jan***

BPharm (Hons), RegPharmNZ

PhD Student / Pharmacist

School of Pharmacy, Faculty of Medical & Health Sciences, The University of Auckland, Private Bag 92019, Auckland, New Zealand.

Ph: +64 9 373 7599 ext 81138. DDI: +64 9 923 1138

F: +64 9 367 7192

*From:*freesurfer-bounces@nmr.mgh.harvard.edu [mailto:freesurfer-bounces@nmr.mgh.harvard.edu] *On Behalf Of *Douglas Greve *Sent:* Friday, 20 July 2012 11:52 a.m. *To:* freesurfer@nmr.mgh.harvard.edu *Subject:* Re: [Freesurfer] slice-by-slice predictors

Sorry, not possible.

On 7/19/12 6:56 PM, Caspar M. Schwiedrzik wrote:

Hi! Is it possible to have slice-by-slice predictors in Freesurfer, and if so, how? Thanks, Caspar

---

Freesurfer mailing list Freesurfer@nmr.mgh.harvard.edu mailto:Freesurfer@nmr.mgh.harvard.edu https://mail.nmr.mgh.harvard.edu/mailman/listinfo/freesurfer

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-- Douglas N. Greve, Ph.D. MGH-NMR Center greve@nmr.mgh.harvard.edu Phone Number: 617-724-2358 Fax: 617-726-7422

Bugs: surfer.nmr.mgh.harvard.edu/fswiki/BugReporting FileDrop: www.nmr.mgh.harvard.edu/facility/filedrop/index.html

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