Novel insular neuromodulation method to alter brain connectivity and reduce cigarette craving in smokers

University Of Colorado Denver, Aurora CO

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Abstract

? DESCRIPTION (provided by applicant): 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.