Brain Activity and Smoking Cessation
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.
|Study Design:||Observational Model: Case-Crossover
Time Perspective: Prospective
|Official Title:||Neural Mechanisms Underlying Smoking Relapse (Center for Interdisciplinary Research on Nicotine Addiction - CIRNA)|
- Association between brain activity following nicotine abstinence and quit rates after 8 weeks post-target quit date [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]The correlation between cerebral blood flow or BOLD signal changes and days to relapse will be examined using separate GLM analyses. For this analysis, each session's (abstinence, smoking) mean CBF (or BOLD signal) will be calculated for the ROIs. Mean values from each ROI will be used as predictors in a longitudinal logistic regression model of quitting success.
- Behavioral performance and BOLD signal change during neurocognitive tasks [ Time Frame: 24 hours ] [ Designated as safety issue: No ]To test effect of abstinence on BOLD signal during performance of various tasks, subject-level contrast maps will be entered into a voxelwise repeated-measures session (abstinent, smoking) by ANOVA. The resulting SPM maps will be transformed to unit normal distribution SPM maps and corrected for multiple comparisons (p < 0.05) using familywise error (FWE) theory and small volume correction (SVC) procedures.
- Cravings for Cigarettes [ Time Frame: 24 hours ] [ Designated as safety issue: No ]During scanning sessions this assessment will be administered during the Smoking Cue task before the cue exposures, once during the task, and at the end of the task.
Biospecimen Retention: Samples With DNA
- A 2ml saliva sample for DNA collection & genotyping (Oragene™).
- A 5ml saliva sample to assess nicotine metabolites (e.g. cotinine and 3-hydroxycotinine).
|Study Start Date:||April 2010|
|Study Completion Date:||February 2013|
|Primary Completion Date:||February 2013 (Final data collection date for primary outcome measure)|
Smoking Cessation Counseling
Individuals will receive individual and group counseling for 8 weeks (6 visits) while they quit smoking.
Behavioral: Smoking Cessation Counseling
Participants shall all receive 8 weeks (6 weeks) of group or individual counseling during their quit attempt.
Other Name: Counseling
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.
|United States, Pennsylvania|
|3535 Market Street, Suite 4100, University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104|
|Principal Investigator:||Caryn Lerman, PhD||University of Pennsylvania|