title: Neural bases of pharmacological treatment of nicotine dependence - insights from functional brain imaging: a systematic review.
abstract: BACKGROUND
  Nicotine dependence is difficult to treat, and the biological mechanisms that are involved are not entirely clear. There is an urgent need to develop better drugs and more effective treatments for clinical practice. A critical step towards accelerating progress in medication development is to understand the neurobehavioral effects of pharmacotherapies on clinical characteristics associated with nicotine dependence.
  
  
  OBJECTIVE
  This review sought to summarize the functional magnetic resonance imaging (fMRI) literature on smoking cessation with the aim to better understand the neural processes underlying the effects of nicotinic and non-nicotinic pharmacological smoking cessation treatments on specific symptoms of nicotine dependence and withdrawal.
  
  
  METHODS
  We conducted a search in Pubmed, Web of Science and PsycINFO databases with the keywords 'fMRI' or 'functional magnetic resonance imaging' and 'tobacco' or 'nicotine' or 'smok*'. The date of the most recent search was May 2012.
  
  
  METHODS
  The original studies that were included were those of smokers or nicotine-dependent individuals, published in the English language, with pharmacological treatment for nicotine dependence and use of fMRI with blood oxygen level-dependent (BOLD) imaging or continuous arterial spin labelling (CASL). No date limit was applied.
  
  
  METHODS
  Two of the authors read the abstracts of all studies found in the search (n = 1,260). The inclusion and exclusion criteria were applied, and 1,224 articles were excluded. In a second step, the same authors read the remaining 36 studies. Nineteen of the 36 articles were excluded. The results were tabulated by the number of individuals and their mean age, the main sample characteristics, smoking status, study type and methodology, and the main fMRI findings.
  
  
  RESULTS
  Seventeen original fMRI studies involving pharmacological treatment of smokers were selected. The anterior and posterior cingulate cortex, medial and lateral orbitofrontal cortex, ventral striatum, amygdala, thalamus and insula are heavily involved in the maintenance of smoking and nicotine withdrawal. The effects of varenicline and bupropion in alleviating withdrawal symptoms and decreasing smoking correlated with modulation of the activities of these areas. Nicotine replacement therapy seems to improve cognitive symptoms related to withdrawal especially by modulating activities of the default-network regions; however, nicotine replacement does not necessarily alter the activities of neural circuits, such as the cingulate cortices, that are associated with nicotine addiction.
  
  
  CONCLUSIONS
  The risk of bias in individual studies, and across studies, was not assessed, and no method of handling data and combining results of studies was carried out. Most importantly, positron emission tomography (PET) studies were not included in this review.
  
  
  CONCLUSIONS
  fMRI studies delineate brain systems that contribute to cognitive deficits and reactivity to stimuli that generate the desire to smoke. Nicotinic and non-nicotinic pharmacotherapy may reduce smoking via distinct neural mechanisms of action. These findings should contribute to the development of new medications and discovery of early markers of the therapeutic response of cigarette smokers.
authors.affiliation: Disciplinas de Psiquiatria e Psicologia Médica da Faculdade de Medicina do ABC, Av. Lauro Gomes, 2000 - Vila Sacadura Cabral, Santo André, SP, 09060-870, Brazil.
authors.forename: Henrique Soila
authors.initials: HS
authors.lastname: Menossi
authors.forename: Anna E
authors.initials: AE
authors.lastname: Goudriaan
authors.forename: Cintia
authors.initials: C
authors.lastname: de Azevedo-Marques Périco
authors.forename: Sérgio
authors.initials: S
authors.lastname: Nicastri
authors.forename: Arthur Guerra
authors.initials: AG
authors.lastname: de Andrade
authors.forename: Gilberto
authors.initials: G
authors.lastname: D'Elia
authors.forename: Chiang-Shan R
authors.initials: CS
authors.lastname: Li
authors.forename: João Mauricio
authors.initials: JM
authors.lastname: Castaldelli-Maia
mesh_terms: D001921:Brain / Q000503:physiopathology*; D055808:Drug Discovery; D006801:Humans; D008279:Magnetic Resonance Imaging; D016032:Randomized Controlled Trials as Topic; D016540:Smoking Cessation / Q000523:psychology*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology / Q000523:psychology; D014029:Tobacco Use Disorder / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology