Smoking Cessation Induced by Deep Repetitive Transcranial Magnetic Stimulation of the Prefrontal and Insular Cortices: A Prospective, Randomized Controlled Trial. Author: Dinur-Klein L1, Dannon P2, Hadar A3, Rosenberg O2, Roth Y3, Kotler M2, Zangen A4. Affiliation: 1Beer Yaakov Mental Health Center, Tel Aviv University, Israel; Department of Life Science, Ben-Gurion University, Beer-Sheva, Israel. 2Beer Yaakov Mental Health Center, Tel Aviv University, Israel. 3Department of Life Science, Ben-Gurion University, Beer-Sheva, Israel. 4Department of Life Science, Ben-Gurion University, Beer-Sheva, Israel. Electronic address: azangen@bgu.ac.il. Conference/Journal: Biol Psychiatry. Date published: 2014 Jun 5 Other: Pages: S0006-3223(14)00387-4 , Special Notes: doi: 10.1016/j.biopsych.2014.05.020 , Word Count: 263 Abstract BACKGROUND: Tobacco smoking is the leading cause of preventable death in developed countries. Our previous studies in animal models and humans suggest that repeated activation of cue-induced craving networks followed by electromagnetic stimulation of the dorsal prefrontal cortex (PFC) can cause lasting reductions in drug craving and consumption. We hypothesized that disruption of these circuitries by deep transcranial magnetic stimulation (TMS) of the PFC and insula bilaterally can induce smoking cessation. METHODS: Adults (N = 115) who smoke at least 20 cigarettes/day and failed previous treatments were recruited from the general population. Participants were randomized to receive 13 daily sessions of high-frequency, low-frequency or sham stimulation following, or without, presentation of smoking cues. Deep TMS was administered using an H-coil version targeting the lateral PFC and insula bilaterally. Cigarette consumption was evaluated during the treatment by measuring cotinine levels in urine samples and recording participants' self-reports as a primary outcome variable. Dependence and craving were assessed using standardized questionnaires. RESULTS: High (but not low) frequency deep TMS treatment significantly reduced cigarette consumption and nicotine dependence. The combination of this treatment with exposure to smoking cues enhanced reduction in cigarette consumption leading to an abstinence rate of 44% at the end of the treatment and an estimated 33% 6 months following the treatment. CONCLUSIONS: This study further implicates the lateral PFC and insula in nicotine addiction and suggests the use of deep high-frequency TMS of these regions following presentation of smoking cues as a promising treatment strategy. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved. KEYWORDS: Addiction; H-coil; TMS; insula; nicotine; prefrontal cortex; smoking PMID: 25038985