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

Identifying predictors of treatment outcome for nicotine use disorders (NUDs) 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 NUD (male n = 91, ages 18-55 years) received a functional magnetic resonance imaging scan during a visual cue task during which they were presented with a series of smoking-related 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 blood-oxygen-level dependent signal during smoke cues and that during food cues for each individual. Food cues were associated with greater deactivation compared with smoke cues in the DMN. In 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, ß = -0.766). An exploratory analysis of executive control and salience networks demonstrated that a more positive Smoke - Food difference score for executive control network 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 a direct clinical relevance in NUD.

An Examination of Behavioral and Neuronal Effects of Comorbid Traumatic Brain Injury and Alcohol Use.

BACKGROUND: Chronic alcohol use disorders (AUDs) and traumatic brain injury (TBI) are highly comorbid and share commonly affected neuronal substrates (i.e., prefrontal cortex, limbic system, and cerebellum). However, no studies have examined how combined physical trauma and heavy drinking affect neurocircuitry relative to heavy drinking alone. METHODS: The current study investigated whether comorbid AUDs and mild or moderate TBI (AUDs+TBI) would negatively affect maladaptive drinking behaviors (n = 90 AUDs+TBI; n = 62 AUDs) as well as brain structure (i.e., increased atrophy; n = 62 AUDs+TBI; n = 44 AUDs) and function (i.e., activation during gustatory cue reactivity; n = 55 AUDs+TBI; n = 37 AUDs) relative to AUDs alone. RESULTS: Participants reported a much higher incidence of trauma (59.2%) compared with the general population. There were no differences in demographic and clinical measures between groups, suggesting that they were well matched. Although maladaptive drinking behaviors tended to be worse for the AUDs+TBI group, effect sizes were small and not statistically significant. Increased alcohol-cue reactivity was observed in bilateral anterior insula and orbitofrontal cortex, anterior cingulate cortex, medial prefrontal cortex, posterior cingulate cortex, dorsal striatum, thalamus, brainstem, and cerebellum across both groups relative to a carefully matched appetitive control. However, there were no significant differences in structural integrity or functional activation between AUDs+TBI and AUDs participants, even when controlling for AUD severity. CONCLUSIONS: Current results indicate that a combined history of mild or moderate TBI was not sufficient to alter drinking behaviors and/or underlying neurocircuitry at detectable levels relative to heavy drinking alone. Future studies should examine the potential long-term effects of combined alcohol and trauma on brain functioning.

Moderators of smoking cessation outcomes in a randomized-controlled trial of varenicline versus placebo.

RATIONALE AND OBJECTIVE: Varenicline has gained a reputation as the optimal intervention for treatment resistant smokers, yet more than half of those who try it do not succeed. To better understand individual differences in the effectiveness of varenicline, this study evaluates the effectiveness of varenicline for smoking cessation in a double-blind, placebo-controlled, randomized clinical trial and examines the influence of psychological factors on treatment outcome. METHOD: Two hundred five cigarette smokers interested in quitting were randomly assigned to 12 weeks of varenicline or placebo. Outcomes examined were CO-confirmed continuous abstinence for the past month, average number of cigarettes smoked per day, and 7-day point prevalence. RESULTS: Varenicline-treated participants were more likely than placebo to achieve continuous abstinence at the end of treatment (OR = 3.29; RR = 2.62), and 7-day point prevalence rates showed an effect of medication at each time point. Participants in both groups significantly reduced their smoking during the course of treatment and follow-up, and the medication by visit interaction was significant in the expected direction. Impulsivity and personality style emerged as moderators of the relationship between medication condition and treatment outcome. CONCLUSIONS: In addition to replicating efficacy results for varenicline versus placebo, the present study shows that the efficacy of pharmacotherapy is influenced by psychological factors. In an era where pharmacotherapy is often perceived as the "silver bullet," we are reminded that smoking cessation is a dynamic process and intervention must be adaptable to address individual differences.

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

Altered resting state functional connectivity (rsFC) and functional network connectivity (FNC), which is a measure of coherence between brain networks, may be associated with nicotine use disorder (NUD). We hypothesized that higher connectivity between insula and 1) dorsal anterior cingulate cortex (dACC) and 2) dorsolateral prefrontal cortex (dlPFC) would predict better treatment outcomes. We also performed an exploratory analysis of the associations between FNC values between additional key frontal and striatal regions and treatment outcomes. One hundred and forty four individuals with NUD underwent a resting state session during functional MRI prior to randomization to treatment with varenicline (n=82) or placebo. Group independent component analysis (ICA) was utilized to extract individual subject components and time series from intrinsic connectivity networks in aforementioned regions, and FNC between all possible pairs were calculated. Higher FNC between insula and dACC (rho=0.21) was significantly correlated with lower levels of baseline smoking quantity but did not predict treatment outcome upon controlling for baseline smoking. Higher FNC between putamen and dACC, caudate and dACC, and caudate and dlPFC significantly predicted worse treatment outcome in participants reporting high subjective withdrawal before the scan. FNC between key regions hold promise as biomarkers to predict outcome in NUD.