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

Abstract

Importance: Tobacco use disorder is associated with dysregulated neurocognitive function in the right inferior frontal gyrus (IFG)-one node in a corticothalamic inhibitory control (IC) network.

Objective: To examine associations between IC neural circuitry structure and function and lapse/relapse vulnerability in 2 independent studies of adult smokers.

Design, setting, and participants: In 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 measures: Associations between corticothalamic-mediated IC, gray-matter volume, and smoking lapse/relapse.

Results: Of 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 relevance: In 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.

Conflict of interest statement

Conflict of Interest Disclosures: None reported.

Figures

Figure 1. Associations Between Inhibitory Control (IC) Blood Oxygenation Level–Dependent (BOLD) Response and Smoking Outcomes

A, In study 1 (cessation study), abstinent smokers exhibited less baseline (ie, prequit attempt) IC task-related BOLD response in the right inferior frontal gyrus (IFG) (yellow cluster in top figure) and right thalamus (yellow cluster in bottom figure) than did smokers who relapsed (P<.001 cluster-determining threshold, cluster extent >186 mm3; 3dClustSim autocorrelation function) (eTable 3 in the Supplement). Error bars represent 1 SE. B, In study 2 (laboratory study), greater BOLD response in the right IFG during IC predicted a shorter time to smoke during the smoking relapse analog task (SRT) (β = −0.468; P = .02; adjusted R2 = 0.151) (eTable 3 in the Supplement). All imaging data were analyzed within an IC network mask (eFigure 2 in the Supplement).

Figure 2. Associations Between Corticothalamic Task-Based Functional Connectivity (tbFC) During Inhibitory Control (IC) and Smoking Outcomes

A, In study 1 (cessation study), smokers who remained abstinent exhibited stronger baseline corticothalamic tbFC during IC than smokers who relapsed at baseline (ie, prequit attempt) (P = .02) (eTable 7 in the Supplement). Error bars represent 1 SE. B, In study 2 (laboratory study), stronger corticothalamic tbFC during inhibitory control predicted a longer time to initiate smoking on the smoking relapse analog task (SRT) (β = 0.791; P < .001, adjusted R2 = 0.538) (eTable 7 in the Supplement).

Figure 3. Corticothalamic Task-Based Functional Connectivity (tbFC) During Inhibitory Control (IC) Mediates the Association Between IC Task Accuracy and Smoking Outcomes

A, In study 1 (cessation study), there was a significant indirect effect of IC task accuracy on smoking relapse outcomes via corticothalamic task-based functional connectivity (tbFC) such that increasing IC task accuracy and corticothalamic tbFC predicted maintaining abstinence (βi = −0.0078; bias-corrected and accelerated [BCa] 95%CI, −0.022 to −0.0002 [binary coding: abstinent, 0; relapsed,1]). B, In study 2 (laboratory study), the indirect effect of IC task accuracy via tbFC accounted for 51.7%of the total effect on time to smoke during the smoking relapse analog task (βi = 0.25; BCa 95%CI, 0.02 to 0.66). eTable 8 in the Supplement provides additional details. aSignificant at P < .05. bP = .07.