Running Head: Insula Connectivity and Smoking Cessation Outcomes

Running Head: Insula connectivity and smoking cessation outcomes

Supplementary Information

Title: Increasedfunctional connectivity in an insula-based network is associated with improved smoking cessation outcomes.

Authors: Merideth A. Addicotta,b, Maggie M. Sweitzera,b, Brett Froeligerc, Jed E. Rosea, Francis J. McClernona,b

Author Affiliations:

aDepartment of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham NC USA 27710

bDuke-UNC Brain Imaging and Analysis Center, Duke University School of Medicine, Durham NC USA 27710

cDepartment of Neurosciences, Medical University of South Carolina, Charleston SC USA 29403

Post hoc Analyses

We explored whether the regions connected with the right p-INS were part of a larger connectivity network. Using MarsBar(1), four separate ROIs were created (right and left putamen clusters and right and left pre- and postcentral gyrus clusters) using the group difference contrast (Nonrelapsed > Relapsed) for the right p-INS. These ROIs were subsequently used as seed regions ina post hoc connectivity analysis. In the Nonrelapsed > Relapsed contrast, each of these seed regions revealed connectivity with the right and/or left posterior insula, and little or no connectivity with any other brain region (p < 0.05, cluster-corrected).

Using an intent-to-treat approach, participants lost to contact during the 10-week follow-up period were considered to have relapsed smoking on the last date of contact and were included in the Relapsed Group. However, we do not have full knowledge of whether or not they actually relapsed; therefore, we re-ran the functional connectivity analysis of our primary result without the participants lost to contact.

Using the right posterior insula subdivision as a seed region, the Nonrelapsed Group (n = 44) had greater functional connectivity than the Relapsed Group (n = 27) with bilateral precentral and postcentral gyri, bilateral planumpolare, and the right putamen(p < 0.05, cluster-corrected); see Table S1 and Figure S2. Using the left posterior insula subdivision as a seed region, the Nonrelapsed Group had greater functional connectivity than the Relapsed Group with bilateral precentral and postcentral gyri, the supplementary motor area, and the left planumpolare(p < 0.05, cluster-corrected); see Table S1 and Figure S3. This complements the results of the larger sample and supports our conclusions concerning the connectivity between the posterior insula and the primary sensorimotor regions.

A notable difference in the results of the smaller sample is that the Relapsed Group had greater connectivity than the Nonrelapsed Group between the left and right posterior insula and the precuneus/posterior cingulate(p < 0.05, cluster-corrected), see Table S1 and Figures S2 and S3.

References

1.Brett M, Anton J-L, Valabregue R, and Poline J-B. Region of interest analysis using an SPM toolbox [abstract]. in 8th International Conference on Functional Mapping of the Human Brain. 2002. Sendai, Japan.

Figure Legends

Figure S1. Functional connectivity with right whole insula seed region of interest.FWE-corrected p < 0.001, KE > 100 voxels.

Figure S2. Group differences in functional connectivity with the right posterior insula segment after excluding participants lost to contact from the Relapsed Group. Regions of greater connectivity in Nonrelapsed Group > Relapsed Group are shown in red. Regions of greater connectivity in Relapsed Group > Nonrelapsed Group are shown in blue (p < 0.05, cluster-corrected). Colorbars indicate T-values.

Figure S3. Group differences in functional connectivity with the left posterior insula segment after excluding participants lost to contact from the Relapsed Group. Regions of greater connectivity in Nonrelapsed Group > Relapsed Group are shown in red. Regions of greater connectivity in Relapsed Group > Nonrelapsed Group are shown in blue (p < 0.05, cluster-corrected). Colorbars indicate T-values.