Default mode network deactivation to smoking cue relative to food cue predicts treatment outcome in nicotine use disorder

Abstract

Identifying predictors of treatment outcome for nicotine use disorders (NUD) may help improve efficacy of established treatments, like varenicline. Brain reactivity to drug-stimuli predicts relapse risk in nicotine and other substance use disorders in some studies. Activity in the default mode network (DMN) is affected by drug cues and other palatable cues, but its clinical significance is unclear. In this study, 143 individuals with nicotine use disorder (NUD) (male n=91, ages 18–55) received a functional MRI scan during a visual cue task during which they were presented with a series of smoking- or food-related video clips prior to randomization to treatment with varenicline (n=80) or placebo. Group independent components analysis was utilized to isolate the DMN, and temporal sorting was used to calculate the difference between the DMN BOLD signal during smoke versus food cues for each individual. Food cues were associated with greater deactivation compared to smoke cues in the DMN. Correcting for baseline smoking and other clinical variables which have been shown to be related to treatment outcome in previous work, a less positive Smoke-Food difference score predicted greater smoking at 6 and 12 weeks when both treatment groups were combined (p=0.005, beta=−0.766). An exploratory analysis of executive control (ECN) and salience networks demonstrated that a more positive Smoke-Food difference score for ECN predicted a more robust response to varenicline relative to placebo. These findings provide further support to theories that brain reactivity to palatable cues, and in particular in DMN, may have direct clinical relevance in NUD.

Neural cue reactivity during acute abstinence predicts short‐term smoking relapse

“…However, changes in the degree of connectivity between these regions have been associated with cue reactivity, nicotine dependence, and smoking cessation outcomes. For example, a study by Wilcox et al found that food cues were associated with greater deactivation of the default mode network compared with smoking cues . This is consistent with previous findings that the default mode network is less suppressed during smoking cue exposure .…”

“…The same regions are also implicated in networks at rest such as the default mode network and salience networks, which are associated with interoceptive processing and attention . Alterations in connectivity of regions involved in interoceptive processing and attention have been associated with smoking cue reactivity and smoking cessation outcomes . Exposure to smoking cues may divert attentional resources towards processing cues and trigger behavior resulting in relapse.…”

Functional network connectivity predicts treatment outcome during treatment of nicotine use disorder

“…More robust outcome predictors are needed as, so far, few self-report measures have proven to be reliable. For example, even self-reported nicotine dependence severity shows inconsistent predictive value (Berlin et al, 2016; McPherson et al, 2014), and recent work in the same subject sample examined in the present manuscript found that a variety of predictors previously identified (mood, impulsiveness, age) were not predictive of treatment outcome (Wilcox et al, 2017). …”

Effects of Cigarette Smoking on Resting-State Functional Connectivity of the Nucleus Basalis of Meynert in Mild Cognitive Impairment

“…In addition, as for smoking addiction, the precuneus is also recognized as an important contributor to cue reactivity in smokers, through its role in attentional bias toward smoking cues ( Engelmann et al, 2012 ; Courtney et al, 2014 ). The abnormal brain activity of the precuneus/DMN has also been observed in healthy smokers ( Weiland et al, 2015 ; Chen and Mo, 2017 ; Zhang et al, 2017 ; Wilcox et al, 2018 ). It should be noted that cholinergic systems play a vital role in cognitive resilience and brain plasticity ( Drever et al, 2011 ).…”