Original Article

Neuropsychopharmacology (2015) 40, 2648–2656; doi:10.1038/npp.2015.114; published online 13 May 2015

Increased Functional Connectivity in an Insula-Based Network is Associated with Improved Smoking Cessation Outcomes

Merideth A Addicott1,2, Maggie M Sweitzer1,2, Brett Froeliger3, Jed E Rose1 and Francis J McClernon1,2

  1. 1Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA
  2. 2Duke-UNC Brain Imaging and Analysis Center, Duke University School of Medicine, Durham, NC, USA
  3. 3Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA

Correspondence: Dr M Addicott, Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Box 3527, Lakeview Pavilion E Suite 300, Durham, NC 27705, USA, Tel: +1 919 684 5237, Fax: +1 919 681 0016, E-mail: merideth.addicott@duke.edu

Received 3 February 2015; Revised 13 April 2015; Accepted 14 April 2015
Accepted article preview online 21 April 2015; Advance online publication 13 May 2015



Little is known regarding the underlying neurobiology of smoking cessation. Neuroimaging studies indicate a role for the insula in connecting the interoceptive awareness of tobacco craving with a larger brain network that motivates smoking. We investigated differences in insula-based functional connectivity between smokers who did not relapse during a quit attempt vs those who relapsed. Smokers (n=85) underwent a resting-state functional connectivity scan and were then randomized into two groups (either smoking usual brand cigarettes or smoking very low nicotine cigarettes plus nicotine replacement therapy) for 30 days before their target quit date. Following the quit date, all participants received nicotine replacement therapy and their smoking behavior was observed for 10 weeks. Participants were subsequently classified as nonrelapsed (n=44) or relapsed (i.e., seven consecutive days of smoking greater than or equal to1 cigarette/day; n=41). The right and left insula, as well as insula subdivisions (posterior, ventroanterior, and dorsoanterior) were used as seed regions of interest in the connectivity analysis. Using the right and left whole-insula seed regions, the nonrelapsed group had greater functional connectivity than the relapsed group with the bilateral pre- and postcentral gyri. This effect was isolated to the right and left posterior insula seed regions. Our results suggest that relapse vulnerability is associated with weaker connectivity between the posterior insula and primary sensorimotor cortices. Perhaps greater connectivity in this network improves the ability to inhibit a motor response to cigarette cravings when those cravings conflict with a goal to remain abstinent. These results are consistent with recent studies demonstrating a positive relationship between insula-related functional connectivity and cessation likelihood among neurologically intact smokers.

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