title: Smoking cessation induced by deep repetitive transcranial magnetic stimulation of the prefrontal and insular cortices: a prospective, randomized controlled trial.
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.
authors.affiliation: Beer Yaakov Mental Health Center, Tel Aviv University, Israel; Department of Life Science, Ben-Gurion University, Beer-Sheva, Israel.
authors.forename: Limor
authors.initials: L
authors.lastname: Dinur-Klein
authors.affiliation: Beer Yaakov Mental Health Center, Tel Aviv University, Israel.
authors.forename: Pinhas
authors.initials: P
authors.lastname: Dannon
authors.affiliation: Department of Life Science, Ben-Gurion University, Beer-Sheva, Israel.
authors.forename: Aviad
authors.initials: A
authors.lastname: Hadar
authors.affiliation: Beer Yaakov Mental Health Center, Tel Aviv University, Israel.
authors.forename: Oded
authors.initials: O
authors.lastname: Rosenberg
authors.affiliation: Department of Life Science, Ben-Gurion University, Beer-Sheva, Israel.
authors.forename: Yiftach
authors.initials: Y
authors.lastname: Roth
authors.affiliation: Beer Yaakov Mental Health Center, Tel Aviv University, Israel.
authors.forename: Moshe
authors.initials: M
authors.lastname: Kotler
authors.affiliation: Department of Life Science, Ben-Gurion University, Beer-Sheva, Israel. Electronic address: azangen@bgu.ac.il.
authors.forename: Abraham
authors.initials: A
authors.lastname: Zangen
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001703:Biophysics; D002540:Cerebral Cortex / Q000502:physiology*; D003367:Cotinine / Q000652:urine; D003404:Creatinine / Q000652:urine; D003463:Cues; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000502:physiology*; D011446:Prospective Studies; D057566:Self Report; D012907:Smoking / Q000523:psychology / Q000628:therapy* / Q000652:urine; D016540:Smoking Cessation / Q000379:methods*; D011795:Surveys and Questionnaires; D050781:Transcranial Magnetic Stimulation / Q000379:methods*
chemical_list: D003404:Creatinine; D003367:Cotinine
keywords: Addiction; H-coil; TMS; insula; nicotine; prefrontal cortex; smoking