Association Between Baseline Corticothalamic-Mediated Inhibitory Control and Smoking Relapse Vulnerability

Abstract

ImportanceTobacco use disorder is associated with dysregulated neurocognitive function in the right inferior frontal gyrus (IFG)—one node in a corticothalamic inhibitory control (IC) network.ObjectiveTo examine associations between IC neural circuitry structure and function and lapse/relapse vulnerability in 2 independent studies of adult smokers.Design, Setting, and ParticipantsIn study 1, treatment-seeking smokers (n = 81) completed an IC task during functional magnetic resonance imaging (fMRI) before making a quit attempt and then were followed up for 10 weeks after their quit date. In study 2, a separate group of smokers (n = 26) performed the same IC task during fMRI, followed by completing a laboratory-based smoking relapse analog task. Study 1 was performed at Duke University Medical Center between 2008 and 2012; study 2 was conducted at the Medical University of South Carolina between 2013 and 2016. Main Outcomes and MeasuresAssociations between corticothalamic-mediated IC, gray-matter volume, and smoking lapse/relapse.ResultsOf the 81 study participants in study 1 (cessation study), 45 were women (56%), with mean (SD) age, 38.4 (10.2) years. In study 1, smoking relapse was associated with less gray-matter volume (F1,74 = 28.32; familywise error P threshold = 0.03), greater IC task-related blood oxygenation level–dependent (BOLD) response in the right IFG (F1,78 = 14.87) and thalamus (F1,78 = 14.97) (P < .05), and weaker corticothalamic task-based functional connectivity (tbFC) (F1,77 = 5.87; P = .02). Of the 26 participants in study 2 (laboratory study), 15 were women (58%), with mean (SD) age, 34.9 (10.3). Similar to study 1, in study 2, greater IC-BOLD response in the right IFG (t23 = −2.49; β = −0.47; P = .02), and weaker corticothalamic tbFC (t22 = 5.62; β = 0.79; P < .001) were associated with smoking sooner during the smoking relapse-analog task. In both studies, corticothalamic tbFC mediated the association between IC performance and smoking outcomes.Conclusions and RelevanceIn these 2 studies, baseline differences in corticothalamic circuitry function were associated with mediated IC and smoking relapse vulnerability. These findings warrant further examination of interventions for augmenting corticothalamic neurotransmission and enhancing IC during the course of tobacco use disorder treatment.