Tobacco addiction is a costly and often fatal problem. Even with counseling and nicotine replacement therapy,
most smokers relapse following a quit attempt. For many smokers and ex-smokers, cigarette smoking is
provoked by affective distress, which includes cigarette cravings. The ability to cope with this distress and
remain abstinent depends on one's level of distress tolerance, which is the ability to persist in a goal-directed
activity while experiencing physical or affective discomfort. However, a gap in knowledge exists regarding the
neural mechanisms that underlie distress tolerance. Identifying these neural mechanisms and understanding
individual differences in distress tolerance holds promise for the development of new therapies and the
improvement of cessation success through personalized interventions.
Past research has shown that cigarette cravings and other forms of affective distress activate the insula,
which may be the neural hub that connects the awareness of affective distress to motor and cognitive control
regions that determine the subsequent behavioral response (e.g., smoking a cigarette to relieve cravings).
However, previous studies that measured functional activity within brain regions have not provided specific
information about functional connectivity between the insula and other brain regions. This information is vital to
understanding complex behaviors. Based on our preliminary data, our central hypothesis is that insula-based
connectivity underlies distress tolerance behavior in relation to smoking cessation.
To investigate this hypothesis, we will investigate three Aims: Aim 1) examine the relationship between
distress tolerance and insula-based connectivity, Aim 2) identify differences between smokers and ex-
smokers, Aim 3) explore brain correlates of distress tolerance using multimodal fusion analysis. This data-
driven approach will complement our hypotheses regarding insula-based connectivity.
To our knowledge, this is the first study to investigate the neural mechanisms of distress tolerance in the
service of smoking cessation. Furthermore, this study will greatly increase our understanding of why some
smokers succeed in quitting. This measure could be used in the future to identify and treat smokers at
increased risk for distress-related relapse. Thus, successful completion of this study will inform the
development of personalized smoking interventions, as well as identify neural mechanisms that can be
targeted by novel therapeutic techniques.