Neural Mechanisms Underlying Smoking Relapse (Center for Interdisciplinary Research on Nicotine Addiction - CIRNA)
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.
Observational
Observational Model: Case-Crossover, Time Perspective: Prospective
Association between brain activity following nicotine abstinence and quit rates after 8 weeks post-target quit date
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.
8 weeks
No
Caryn Lerman, PhD
Principal Investigator
University of Pennsylvania
United States: Institutional Review Board
811325
NCT01186055
April 2010
February 2013
Name | Location |
---|---|
3535 Market Street, Suite 4100, University of Pennsylvania | Philadelphia, Pennsylvania 19104 |