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

Abstract

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 ⩾1 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.

Figure 1

The left and right whole-insula regions of interest were subdivided into posterior (shown in blue), dorsoanterior (shown in red), and ventroanterior (shown in yellow) segments. Significant main effects of the whole left and right insula seed regions were followed up with the left and right segmented seed regions. A full color version of this figure is available at the Neuropsychopharmacology journal online.

Figure 2

Functional connectivity with the right posterior (shown in blue), dorsoanterior (shown in red), and ventroanterior (shown in yellow) insula segments. Regions of overlapping connectivity between the dorsoanterior and ventroanterior segments are shown in orange, between the dorsoanterior and posterior segments are shown in purple, and among the posterior, dorsoanterior, and ventroanterior segments are shown in brown. FWE-corrected P<0.001, K_E >100 voxels.

Figure 3

Group differences (nonrelapsed group >relapsed group) in functional connectivity using the right posterior (shown in blue), dorsoanterior (shown in red), and ventroanterior (shown in yellow) insula segments as a seed regions of interest. Cluster corrected, P<0.05. Color bars indicate T-values. A full color version of this figure is available at the Neuropsychopharmacology journal online.