Many smokers attempt to quit every year, but 90% relapse within 12 months. Converging evidence suggests relapse is associated with insufficient activation of the prefrontal cortex. Delay discounting rate reflects relative activity in brain regions associated with relapse. High-frequency repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (LDLPFC) increases cortical excitability and reduces delay discounting rates, but little is known about feasibility, tolerability, and potential efficacy for smoking cessation. We hypothesized that 8 sessions of 20Hz rTMS of the LDLPFC combined with an evidence-based self-help intervention will demonstrate feasibility, tolerability, and potential efficacy in a limited double-blind randomized control trial. Smokers (n=29), abstinent for 24h, motivated to quit, and not using cessation medications, were randomized to active 20Hz rTMS at 110% of Motor Threshold or sham stimulation that replicated the look and sound of active stimulation. Stimulation site was located using the 6cm rule and neuro-navigation. Multiple clinical, feasibility, tolerability, and efficacy measures were examined. Active rTMS decreased delay discounting of $100 (F (1, 25.3694)=4.14, p=.05) and $1000 (F (1, 25.169)=8.42, p<.01), reduced the relative risk of relapse 3-fold (RR 0.29, CI 0.10-0.76, Likelihood ratio χ2 with 1 df=6.40, p=.01), increased abstinence rates (active 50% vs. sham 15.4%, Χ (df=1)=3.80, p=.05), and increased uptake of the self-help intervention. Clinical, feasibility, and tolerability assessments were favorable. Combining 20Hz rTMS of the LDLPFC with an evidence-based self-help intervention is feasible, well-tolerated, and demonstrates potential efficacy.

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Socioeconomic disparities in treatment failure rates for evidence-based tobacco dependence treatment are well-established. Adapted cognitive behavioral treatments are extensively tailored to meet the needs of lower socioeconomic status (SES) smokers and dramatically improve early treatment success, but there is little understanding of why treatment failure occurs after a longer period of abstinence than with standard treatment, why early treatment success is not sustained, and why long-term treatment failure rates are no different from standard treatments. We sought to understand the causes of treatment failure from the perspective of diverse participants who relapsed after receiving standard or adapted treatment in a randomized control trial. We used a qualitative approach and a cognitive-behavioral framework to examine themes in responses to a semi-structured post-relapse telephone interview. The primary causes of relapse were familiar (i.e., habit, stress, unanticipated precipitating events). The adapted treatment appeared to improve the management of habits and stress short-term, but did not adequately prepare respondents for unanticipated events. Respondents reported that they would have benefited from continued support. New therapeutic targets might include innovative methods to reduce long-term treatment failure by delivering extended relapse prevention interventions to support early treatment success.Trial Registration: Clinicaltrials.gov NCT02785536.

Background.-Delay discounting rate shows robust predictive validity for tobacco use behaviors and is a new therapeutic target in the treatment of tobacco use. Identifying factors that influence relations between delay discounting and the choice to smoke cigarettes is key to the development of effective interventions that target delay discounting to reduce cigarette consumption. Objective.-To examine relations between delay discounting, motivational factors, self-efficacy, nicotine dependence level, and the proximal choice to smoke in the context of other commonly rewarding activity choices. Methods.-In this cross-sectional design, daily smokers (n=480) from Amazon Mechanical Turk completed a questionnaire that assessed delay discounting rate; motivation, intention, and selfefficacy to quit smoking; nicotine dependence level, and the preference for immediately engaging in multiple commonly rewarding activities. We hypothesized that 1) greater motivation to quit would be associated with lower priority given to smoking; 2) the relation between delay discounting and the priority given to smoking would be mediated by motivation, self-efficacy, and nicotine dependence level. Results.-Greater motivation to quit was significantly associated with a lower priority given to smoking. The relation between delay discounting and the priority given to smoking was marginally mediated by nicotine dependence level (p > .057). Conclusions.-Motivation to quit influences decision-making by impacting the prioritization of choices. Nicotine dependence is likely to mediate the relation between delay discounting and the choice to smoke. Interventions that target delay discounting to reduce cigarette consumption or prevent relapse need to account for motivation to quit and nicotine dependence level.