Short communicationInsula reactivity to negative stimuli is associated with daily cigarette use: A preliminary investigation using the Human Connectome Database
Introduction
Over 36 million adults in the United States smoke cigarettes daily (Centers for Disease Control and Prevention (CDC), 2010), yet the number of cigarettes smoked/day varies across individuals (Shiffman, 2009, Burns et al., 1997). Understanding factors influencing smoking rates is essential, as greater smoking rates are associated with increased risk of smoking related illness (Bjartveit and Tverdal, 2005, Law and Wald, 2003) and with poorer quit outcomes (Harris et al., 2004, Hymowitz et al., 1997).
One factor possibly mediating daily cigarette use is reactivity to negative affect, as smoking is often maintained to alleviate negative mood states (Copeland et al., 1995, Brandon, 1994, Baker et al., 2004). Smokers self-administer greater numbers of cigarettes/day when faced with exogenous stressors (Aronson et al., 2008) and more rapid relapse is associated with decreased distress tolerance (Brown et al., 2002), suggesting that smoking may be related to how an individual processes negative affect. To test the hypothesis that daily smoking rates are associated with how negative affect is processed, we evaluated the relationship between the number of cigarettes an individual smokes/day and insula reactivity to negative stimuli.
Insula reactivity to negative stimuli in smokers is of particular interest, because this brain region is implicated in affective processing (Critchley, 2002, Critchley et al., 2004, Damasio et al., 2000, Phan et al., 2002, Craig, 2002, Craig, 2010) and smoking (Janes et al., 2010a, Janes et al., 2010b, Naqvi et al., 2007, Gray and Critchley, 2007). The insula is engaged during the processing of basic affective states, including the interpretation of external stimuli such as emotional faces (Carr et al., 2003) and internal awareness of one’s emotions (Critchley, 2002, Critchley et al., 2004, Damasio et al., 2000, Craig, 2002, Craig, 2010). Additionally, the insula facilitates nicotine seeking-behavior (Naqvi et al., 2007, Forget et al., 2010, Scott and Hiroi, 2011, Pushparaj et al., 2013) and is related to factors that impact daily smoking such as cigarette craving (Brody et al., 2002, Wang et al., 2007) and nicotine dependence severity (Claus et al., 2013). Thus, our analysis focused on a previously identified anterior insula region of interest (ROI) that is associated with smoking (Janes et al., 2015).
To identify an association between daily cigarette use and insula reactivity to negative stimuli, we investigated data collected via the Human Connectome Project (HCP; Van Essen et al., 2013). Specifically, we assessed whether the number of cigarettes smoked/day was correlated with insula activity collected during an emotional processing task where individuals were presented with faces expressing negative emotion compared to a neutral control. Given the insula's involvement in both emotional processing and nicotine dependence, we hypothesize that insula reactivity to negative stimuli will be associated with greater daily nicotine use.
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Participants
Data analyzed were obtained from the Human Connectome Project (HCP). A description of the recruitment criteria for the HCP is provided by Van Essen et al. (2013). Briefly, individuals were excluded by the HCP if they reported a significant history of psychiatric disorder, substance abuse, neurological disorder, or medical disorder known to influence brain function. Participants in the current study included all those reporting regular cigarette use who did not have a positive urine sample
Association between Insula reactivity and cigarettes/day
There was a positive association between cigarettes smoked/day and reactivity to negative faces > shapes in the right (Pearson’s r = 0.564, p = 0.008; Fig. 1), but not left anterior insula (Pearson’s r = 0.253, p = 0.268). This finding was supported by non-parametric testing using Spearman’s rho (right anterior insula r = 0.653, p = 0.001). While there was a marginal association between cigarettes smoked/day and beta weights extracted from the right posterior insula (Pearson’s r = 0.446, p = 0.43), this
Discussion
Negative affect is associated with nicotine use (Kassel et al., 2003, Hughes et al., 1994), as ameliorating withdrawal-related negative affect is one of the most cited reasons for precipitating relapse (Copeland et al., 1995, Brandon, 1994, Baker et al., 2004). The current finding expands our understanding of the link between negative affect and daily cigarette use by demonstrating that right anterior insula reactivity to negative stimuli is positively correlated with cigarettes smoked/day.
Role of funding
This study was supported by NIH funded grants: K01 DA029645 (PI Amy Janes) and T32 DA015036 (Supported author ND; PI Scott Lukas). Data were provided by the Human Connectome Project, WU-Minn Consortium (Principal Investigators: David Van Van Essen and Kamil Ugurbil; 1U54MH091657) funded by the 16 NIH Institutes and Centers that support the NIH Blueprint for Neuroscience Research; and by the McDonnell Center for Systems Neuroscience at Washington University.
Contributors
AJ defined the question and guided data analysis and manuscript preparation, ND and AP contributed to data analysis and wrote the manuscript. All authors approved the final version of the manuscript.
Conflict of interest
No conflict declared for any author.
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Authors contributed equally to this work.