Cigarette smoking is the single greatest preventable cause of mortality, morbidity, and health care costs in the United States. In the US, smoking is estimated to cause 443,595 deaths annually and $193 billion per year in smoking-related health care costs and smoking-attributable productivity losses. Nicotine dependence is notoriously difficult to treat, and current treatments are plagued by high rates of relapse. High levels of cigarette craving are known to be associated with relapse. Numerous studies have implicated the insula as a key brain region involved in maintenance of craving and nicotine dependence. Retrospective and prospective human studies have shown that patients with damage to the insula spontaneously or easily stop smoking without cravings. The insula's role has also been demonstrated in animal models using pharmacologic or deep brain stimulation lesions of the insula. One possible way to inhibit the insula is through repetitive transcranial magnetic stimulation (rTMS). rTMS is a neuromodulatory technique in which a pulsatile magnetic field is used to induce depolarization of cortical neurons and affect synaptic activity. High frequency rTMS transiently increases cortical excitability, while low frequency rTMS inhibits it. Previous work has reported that excitatory rTMS targeting the DLPFC modulates craving responses. While most experts in this field acknowledge the critical role of the insula in nicotine dependence, there has been surprisingly little research exploring neuromodulation of the insula as a potential therapy. The literature implicating the insula in maintenance of craving in smokers suggests inhibitory rTMS targeting the insula may provide a more robust modulation of nicotine craving. In a single-blinded two-arm (sham rTMS and inhibitory insular rTMS) randomized control trial with 20 active smokers assigned to each arm, we will collect craving measurements, resting state fMRI, and task-based fMRI before and after a single session of rTMS treatment to investigate the following aims: (1) determine if inhibitory insular rTMS reduces craving, (2) determine if inhibitory insular rTMS alters insular connectivity, and (3) determine if inhibitory insular rTMS alters insular brain activity. This proposal has the potential to improve the health o millions of Americans by providing evidence towards a new, potentially powerful method of treating nicotine dependence.
Cigarette smoking is the single greatest preventable cause of mortality, morbidity, and health care costs in the United States. Nicotine dependence is notoriously difficult to treat, and the risk of relapse is approximately 80% for combined medical and counselling therapy. High levels of cigarette craving are known to be associated with relapse. The insula has been shown to be an important structure involved in cigarette craving; patients and animal models with damage to the insula spontaneously or easily stop craving nicotine. This proposal seeks to characterize a method of noninvasive inhibitory neuromodulation, transcranial magnetic stimulation, to reduce cigarette craving and modulation brain function in current smokers.
| Lind, Kimberly E; Gutierrez, Eric J; Yamamoto, Dorothy J et al. (2017) Sex disparities in substance abuse research: Evaluating 23 years of structural neuroimaging studies. Drug Alcohol Depend 173:92-98 |
| Regner, Michael F; Saenz, Naomi; Maharajh, Keeran et al. (2016) Top-Down Network Effective Connectivity in Abstinent Substance Dependent Individuals. PLoS One 11:e0164818 |
