Enhancing relapse prevention for smoking cessation with rTMS

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DESCRIPTION (provided by applicant): Tobacco use is one of the most significant cancer control and public health challenges today. One in five Americans smoke daily. Half of all smokers will make an attempt to quit each year; but 95% of those who attempt will reverse this decision within 12 months and choose the transient, immediately rewarding activity of smoking at the cost of larger long-term rewards such as future health and long life. This project seeks to improve our scientific knowledge of these decision-making processes and improve tobacco dependence treatments. The dorsolateral prefrontal cortex (DLPFC) influences decision-making by integrating inhibitory mechanisms with emotionally charged information from limbic regions, thereby exerting an inhibitory influence on seductive, immediately rewarding options with long term costs, such as smoking. Delay discounting is the degree to which one de-values delayed outcomes, such as future health and long life. Converging evidence indicates that choosing a delayed option with a larger reward is associated with increased activity in the DLPFC. We propose that choosing to smoke after making a decision to quit reflects a situation where the DLPFC is insufficiently activated to exert an inhibitory influence on the immediately rewarding option of smoking. Preliminary studies indicate that stimulation of the DLPFC with high frequency repetitive Transcranial Magnetic Stimulation (rTMS) reduces delay discounting (i.e., causes individuals to choose delayed, higher value options); reduces cigarette consumption in smokers intending to quit; improves executive function, learning, memory, and attention; is a promising adjunct to cognitive-behavioral treatment of other disorders; and is likely to improve the efficacy of existing cognitive-behavioral treatments for tobacco dependence. Our goal is to make an informed recommendation, based on measures of feasibility,1,2 of whether or not this intervention should be tested for efficacy. We will use a double-blind, randomized between-subjects treatment (active or sham) design in which all subjects are exposed to the same relapse prevention materials during rTMS stimulation. Aim 1: Examine the feasibility of combining high frequency rTMS with an evidence-based, self-help, cognitive-behavioral relapse prevention intervention using multiple feasibility indicators (demand, acceptability, practicality, limited-efficacy testing, and adequate blinding). Aim 2: Examine differences in delay discounting between the active and the sham conditions 2, 4, 8, and 12 weeks after the quit day. Aim 3: Use latency to relapse comparisons to calculate estimates of the effect size of this intervention on abstinence. This exploratory research will promote the early stages of an innovative scientific idea that has the potential to substantially advance the understanding of mechanisms that affect tobacco use and treatment as well as many other aspects of bio-behavioral cancer control research. If ultimately found to be efficacious, the findings will have an impact on the treatment of many dysfunctional health behaviors where individuals have difficulty refusing immediately seductive choices that have serious long-term health consequences.