PROJECT SUMMARY/ABSTRACT Smoking is the leading preventable cause of mortality and morbidity in the United States, each year contributing to approximately 443,000 deaths. Smoking and high relapse rates are likely due to factors that affect both limbic and executive circuits in the brain, including vulnerability to salient smoking-related cues and loss of cognitive control. Accumulating evidence indicates that in addiction, the frontal-striatal circuits involved in limbic reward and impulsive action are relatively hyperactive, while the executive control circuits are relatively hypoactive. Thus, intervention efforts should be directed at either decreasing the relative activity of the impulsive reward circuit or increasing the relative activity of the executive control circuits. Transcranial magnetic stimulation (TMS) is a non-invasive, FDA-approved treatment for depression which is also being investigated for as a possible treatment for smoking cessation. The goal of this project is to use the novel theta burst stimulation (TBS) protocol to induce sustainable decreases and increases in the impulsive and executive control circuits, respectively. To do so, we will apply an attenuating form of TBS to the ventromedial prefrontal cortex to target the impulsive reward circuit and a potentiating form of TBS to the dorsolateral prefrontal cortex to target the executive control circuit. We will then investigate the efficacy of these protocols for reducing a range of smoking measures, including cigarette valuation, delay discounting, cigarette self-administration, and brain reactivity to smoking cues. The results from these investigations will pave a clear pathway for the systematic development of neural-circuit based strategies as treatments for tobacco use and dependence.

NARRATIVE The consequences of cigarette smoking constitute the greatest preventable cause of mortality and morbidity in the US. As a significant conceptual advance in the field, this proposal will evaluate 2 promising neural-circuit based strategies as tools to decrease cigarette demand, use, and the brain reactivity to smoking cues. The results from this 2 site, double blinded proposal will pave a clear pathway for the systematic development of these neural-circuit based strategies as treatments for our patients.