Brain Activity and Smoking Cessation
Condition: Nicotine Dependence
MeSH terms: Tobacco Use Disorder
Study type: Observational

Summary: 
      In the current study, the investigators propose to test: (1) whether brain activation and
      connectivity in a resting state, assessed by ASL perfusion MRI, BOLD fMRI, and diffusion
      tensor imaging (DTI) predicts smoking relapse, and (2) whether brain activation, assessed by
      BOLD fMRI during performance of neurobehavioral probes for executive cognitive function,
      stress and cue reactivity, predicts smoking relapse.
    

Detailed description: 
      Our previous work demonstrated that, among non-treatment seeking smokers, regional cerebral
      blood flow (rCBF) is increased following 14 hours of overnight abstinence, as compared to
      smoking as usual. Specifically, increased rCBF was observed in the anterior cingulate, medial
      and left orbitofrontal cortex. Two smoking urges items ("cravings for a cigarette" and "urges
      to smoke at this time") that predict relapse were strongly correlated with CBF increases in
      several regions that comprise the brain's reward and visual circuitry (Wang et al., 2007). In
      addition, two other studies by our group using BOLD fMRI showed that smokers with genotypes
      associated with smoking relapse exhibit a reduction in BOLD signal in the bilateral
      dorsolateral PFC and MF/CG during nicotine withdrawal as well as impairments in working
      memory at high levels of task difficulty (Loughead et al., 2009). In a follow-up experiment,
      it was found that the smoking cessation medication varenicline reverses this deficit
      (Loughead et al., in press). In the current study, we propose to extend these findings in a
      smoking cessation treatment population by testing: (1) whether brain activation and
      connectivity in a resting state, assessed by ASL perfusion MRI, BOLD fMRI, and diffusion
      tensor imaging (DTI) predicts smoking relapse, and (2) whether brain activation, assessed by
      BOLD fMRI during performance of neurobehavioral probes for executive cognitive function,
      stress and cue reactivity, predicts smoking relapse. Following eligibility screening (week
      0), 100 treatment-seeking smokers will complete two 1.5 hour pre-quit neuroimaging
      assessments (one following 24 hours of overnight abstinence and the other after
      smoking-as-usual (weeks 1 and weeks 2-3; order counterbalanced). All will receive
      standardized behavioral smoking cessation counseling (week 4) to prepare for a scheduled quit
      attempt (week 5). They will make brief visits to the Center (weeks 5, 6, 7, 8 & 9) to receive
      booster counseling and assess smoking status. The primary endpoints for assessing quitting
      success are: 8 weeks post-target quit date (week 13) and 24-weeks post target quit date (week
      29). At the 8-week post-target quit date all participants will be contacted for a telephone
      survey and those who self-report not smoking for the past 7 days will be asked to come to the
      Center for biochemical confirmation. Lastly, a subset of participants (15 smokers who report
      having been abstinent for at least the past 7 days and 15 smokers who relapsed within the
      first few weeks of the TQD) will be asked to complete a third MRI scan to examine changes in
      brain activity related to cessation. Only those participants reporting being quit at this
      time point will be contacted again at 24 weeks. Identification of the neural substrates of
      relapse following a quit attempt could inform the development of novel medications. Further,
      the identification of a "brain signature" that predicts relapse may allow for the use of fMRI
      to screen novel medications and identify those that reverse the liability profile.
    

Intervention name(s): Smoking Cessation Counseling
Intervention type(s): Behavioral
Intervention description(s): Participants shall all receive 8 weeks (6 weeks) of group or individual counseling during their quit attempt.
Other intervention name(s): Counseling
Observational model: Case-Crossover
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        100 treatment seeking smokers ages 18 to 65 who report smoking at least 10 cigarettes per
        day for at least the last 6-months.
      
Biospecimen description: 
      1. A 2ml saliva sample for DNA collection & genotyping (Oragene™).

        2. A 5ml saliva sample to assess nicotine metabolites (e.g. cotinine and
           3-hydroxycotinine).
    
Keywords: Smoking Relapse; Nicotine Abstinence