Abstract
Craving is a core feature of tobacco use disorder as well as a significant predictor of smoking relapse. Studies have shown that appetitive smoking-related stimuli (e.g., someone smoking) trigger significant cravings in smokers impede their self-control capacities and promote drug seeking behavior. In this review, we begin by an overview of functional magnetic resonance imaging (fMRI) studies investigating the neural correlates of smokers to appetitive smoking cues. The literature reveals a complex and vastly distributed neuronal network underlying smokers’ craving response that recruits regions involved in self-referential processing, planning/regulatory processes, emotional responding, attentional biases, and automatic conducts. We then selectively review important factors contributing to the heterogeneity of results that significantly limit the implications of these findings, namely between- (abstinence, smoking expectancies, and self-regulation) and within-studies factors (severity of smoking dependence, sex-differences, motivation to quit, and genetic factors). Remarkably, we found that little to no attention has been devoted to examine the influence of personality traits on the neural correlates of cigarette cravings in fMRI studies. Impulsivity has been linked with craving and relapse in substance and tobacco use, which prompted our research team to examine the influence of impulsivity on cigarette cravings in an fMRI study. We found that the influence of impulsivity on cigarette cravings was mediated by fronto-cingulate mechanisms. Given the high prevalence of cigarette smoking in several psychiatric disorders that are characterized by significant levels of impulsivity, we conclude by identifying psychiatric patients as a target population whose tobacco-smoking habits deserve further behavioral and neuro-imaging investigation.
Introduction
According to recent estimates, there are currently over a billion smokers worldwide and another 300 million are foreseen for 2030 (1). The main issue with these numbers is that smoking harms nearly every organ in the body and is associated with significant disease and mortality (2). Among chronic cigarette smokers, it is estimated that about 50% will eventually be killed by tobacco-related diseases (3). Despite the growing recognition of the harmful health effects of cigarette, many smokers persist in their use and have great difficulty quitting. Although over 70% of smokers want to quit, only 5–17% of quit attempts are successful without proper support (4). For such reasons, tobacco is deemed as one of the most addictive drugs and significant research has been dedicated to the understanding of the psychobiological mechanisms underlying its addictive nature. As craving is a core feature of tobacco use disorder and a significant predictor of smoking relapse (5), several neuro-imaging studies have been performed to elucidate the neural mechanisms underlying smoking motivation. This literature has shown that the brain circuits involved in cigarette craving are not restricted to the classic brain reward system, but also encompass regions involved in self-referential processes and action planning, among others (6). Although we have gained valuable knowledge on the neurophysiology of cigarette cravings, the implications of this literature is limited by the heterogeneity of results. One of the overlooked sources of heterogeneity is impulsivity, a personality trait playing a key role in addiction (7). Recently, our team has published a paper in Frontiers in Psychiatry (8), examining the influence of impulsivity on brain activations triggered by cigarette cues in chronic smokers. Putting this work into context is the aim of the current “focused review”.
KEY CONCEPT 1. Cigarette cravings
Cravings are defined as persistent urges, thoughts or desires to smoke a cigarette. Considered a core feature of tobacco use disorder in the recent DSM-V, cravings are one of the most consistent predictors of relapse in previous smokers.
KEY CONCEPT 2. Impulsivity
Impulsivity is a predisposition toward rapid, unplanned reactions to internal or external stimuli without regard for the negative consequences of these reactions for the impulsive individuals and others.
Appetitive Smoking Cues
The clinical relevance of cue reactivity
For many smokers, the most worrying aspects of quitting are the relentless urges or desires to smoke a cigarette. Cravings tend to decrease in strength and frequency with longer abstinence period, yet a minority of ex-smokers still report strong urges 6 months after quitting (9). Empirical studies have shown that cravings – a core feature of tobacco use disorder in the DSM-V – are one of the most consistent predictors of relapse in ex-users (5), and accordingly their reduction is a primary objective of cessation treatment in smokers.
Craving is often defined as a subjective experience of wanting to use a drug, and thereby orienting oneself toward drug taking. Classical conditioning models stipulate that cravings are situation-specific and persistent, such that they can be triggered by stimuli previously associated with drug use, and reinstated years after abstinence (10). Tiffany and Conklin (11) have complemented this model by arguing that craving is a multifaceted construct that involves various cognitive processes, including memory recollection of past drug taking and expectancy of subsequent use. According to them, drug-taking behaviors may occur in the absence of craving because they become automatized in the transition phase to dependence. The role of craving would therefore consist of cognitive processes that can fuel or prevent the execution of automatized drug use habits.
Craving may be divided into tonic (background) and phasic urges for a drug, both of which have been associated with smoking relapse (5, 12, 13). They, respectively, reflect slowly changing states induced by abstinence, and a peak response with fast onset to appetitive drug cues. In experimental settings, exposure to appetitive smoking-related stimuli (e.g., videos, pictures, a lit cigarette) can trigger intense acute cravings (14) in abstinent smokers, even following a decline in tonic cravings. Likewise, a variety of laboratory stressors can elicit acute cravings in smokers (15). These experimental paradigms offer a clear opportunity to improve our understanding of relapse mechanisms and the inability to quit smoking.
Neural correlates of smokers’ response to appetitive smoking cues
Over the last decade, considerable efforts have been spent on elucidating the neurobiological bases of cigarette cravings. Most studies used functional magnetic resonance imaging (fMRI) and presented pictures or videos (85% of studies) to depict smoking situations likely to provoke cravings. Relative to neutral material, appetitive smoking-related stimuli have been shown to consistently elicit brain activations throughout cortical and sub-cortical regions in both abstinent and non-abstinent smokers (8, 16–25). A meta-analysis by Engelmann et al. (6) showed that during the viewing of appetitive cigarette-related cues, most significant clusters of activations were located within the extended visual cortex, followed by the anterior and posterior cingulate gyri, the medial and dorso-lateral prefrontal cortex, and the superior and middle temporal gyri. Smaller clusters were also observed in the insula and (dorsal) striatum. The widespread brain reactivity to drug cues validates the notion that craving is a multidimensional phenomenon implicating several cognitive processes. Contrary to the postulates of classic theories of drug addiction (10), these findings reveal that the brain craving response is not confined to the brain reward circuitry, and that other key brain regions need to be recruited in order to fully experience the complex craving response. The available results highlight a vastly distributed neuronal network underlying smokers’ cravings, which stresses the importance of attentional/visual processing (extended visual system) (16, 22, 24), self-referential processing [precuneus, posterior cingulate cortex (PCC)] (26–28), planning/regulatory processes [anterior cingulate cortex (ACC) and dorso-lateral prefrontal cortex (dlPFC)] (17, 29), emotional/interoceptive processes (insula) (18, 19, 29–31), and learning of automatic conducts (dorsal striatum) (28, 31, 32). Among these regions, frontal and limbic (insula) sub-regions seem to be the most directly related to the subjective experience of cigarette cravings (33).
In addition to the vast neuro-imaging literature examining brain responses of smokers to appetitive smoking-related material, a few authors have investigated the specific neural correlates of appetitive drug-related processing by comparing it to the processing of appetitive stimuli other than drugs. As hypothesized by Volkow et al. (34), drug addicts displayed a significant decrease in incentive salience toward natural compared to drug rewards, which helps explaining the heightened motivation for drug use observed in this population. Specifically in nicotine dependence, chronic cigarette smokers were found to be more reactive to cigarette cues relative to erotic pictures, whereas the opposite was observed in non-smokers. This difference in brain reactivity between smokers and non-smokers was found in the middle frontal gyrus (Brodmann area 6/8) (35), a region near the supplementary motor area thought to be involved in action planning and expectancy. This suggests a greater orientation, in smokers, toward the appetitive value of drugs than that of natural rewards. Finally, Versace et al. (36) found that smokers having decreased activity in the dorsal striatum while viewing erotic and romantic pictures compared to smoking cues were significantly more likely to have relapsed 6 months after quitting. This suggests that smokers with decreased dorsal striatum activity to pleasant stimuli have greater difficulty quitting. It also suggests that reinforced drug habits promote a biased sensitivity toward the appetitive value of smoking compared to that of other rewards.
Our team has further explored the specificity of the neural correlates of appetitive drug-related processing by contrasting the brain responses of smokers to appetitive and aversive smoking cues (37). The rationale of this study was based on evidence showing that smokers are roused by appetitive smoking stimuli, and that their consumption tends to be only mildly affected by anti-smoking stimuli depicting smoking’s negative value (38, 39). Using fMRI, 30 chronic smokers viewed appetitive smoking-related, aversive smoking-related, and neutral images. Appetitive smoking-related images elicited increased activations in the medial prefrontal cortex (mPFC), the PCC and the precuneus, compared to aversive smoking-related cues. This study demonstrated that smokers recruit brain regions involved in the processing of self-relevant material in response to appetitive smoking cues, compared to anti-smoking stimuli, highlighting a neurophysiologic bias toward the positive, rather than negative, value of smoking.
Sources of Heterogeneity
When looking at individual studies assessing the neural correlates of cigarette craving, one finds that several factors contribute to the heterogeneity of findings between studies, such as abstinence levels, smoking expectancy, and craving suppression. There is also high individual variability within studies in the brain activations associated with exposure to smoking cues. It is therefore crucial to further understand this variability in brain reactivity to appetitive cigarette stimuli. Smoking dependence severity, sex-differences, motivation to quit, and genetic factors have been studied as potential factors of inter-individual variability in cigarette craving-induced brain responses. Comparatively, little attention has been paid to anxiety, depression, and personality traits. Table 1 summarizes the list of factors influencing brain reactivity to appetitive smoking cues.
Table 1
| Variable | Observations | Relevant reference |
|---|---|---|
| Between-study factors | ||
| Abstinence | During abstinence, cue-elicited cravings are more intense, and elicit stronger activations in the rostral anterior cingulate gyrus | (40) |
| Expectancy | Smokers display greater rostral prefrontal cortex activations when they are told that they will be allowed to smoke a cigarette immediately after the scan | (22, 27, 32, 41) |
| Self-regulation of cravings | Smokers display increased recruitment of frontal and cingulate regions when they are actively seeking to resist cigarette cravings | (16, 26, 42, 43) |
| Within-study factors | ||
| Smoking dependence severity | Smoking dependence severity is positively associated with increased brain reactivity to appetitive smoking cues. The brain regions underlying this increased brain reactivity remain to be determined. Heterogeneity of results is a concern | (19, 23, 31, 44–46) |
| Sex-differences | Preliminary results that need to be confirmed suggest that the brain reactivity to appetitive smoking cues in women smokers is increased during the follicular phases of the menstrual cycle | (21, 47) |
| Motivation to quit | Preliminary evidence suggests that motivation influences the brain responses of smokers to appetitive smoking cues | (48, 49) |
| Genetic factors | Preliminary studies have linked dopamine- and acetylcholine-related genetic polymorphisms to the brain reactivity of smokers to appetitive smoking cues | (18, 19, 30) |
| Impulsivity trait | Impulsivity trait is associated with increased cue-elicited cigarette cravings. This relationship may be mediated by fronto-cingulate mechanisms | (8) |
Factors influencing brain reactivity to appetitive smoking cues.
Between-study heterogeneity
Of all the variables that may influence the neural correlates of cue-elicited cigarette cravings, abstinence has been the most studied. On theoretical grounds, Wilson and Sayette (40) proposed that moderate and uncontrollable cravings may trigger substantially different brain responses. Consistently with this idea, the meta-analysis from Engelmann et al. (6) found that studies performed in deprived smokers (who report more intense cravings) had increased activations in the right superior frontal and the left lingual gyrus, relative to studies performed in non-deprived smokers. However, this meta-analysis also showed sizeable overlap between both sets of studies, which produced activations in 44 widespread clusters (6). Recently, Wilson and Sayette (40) updated the meta-analysis of Engelmann et al. (6). By contrasting 24 functional imaging studies involving deprived and non-deprived smokers, this updated meta-analysis showed that deprived smokers elicit stronger activations of the rostral ACC than smokers allowed to smoke ad libitum before the scanning session. Interestingly, the rostral ACC is thought to play a critical role in the neurobiology of addiction, given that it receives dopaminergic inputs from the ventral tegmental area (10) and is involved in self-referential processes (50).
Smoking expectancy has also been shown to influence brain reactivity to appetitive smoking cues in chronic smokers. Wilson et al. (22) found that the expectation of being allowed to smoke a cigarette immediately after the scanning session was associated with increased activations in the ventro-medial PFC, the precentral gyrus, and the right middle temporal gyrus. The same research team subsequently confirmed the influence of smoking on rostral PFC activations, but only in smokers unmotivated to quit (32). Hayashi et al. (41) found that smoking expectancy is associated with increased activation in the dlPFC. Finally, McBride et al. (27) found an association between smoking expectancy and activations in several frontal regions (dlPFC, dACC, dmPFC, mOFC), the PCC, and the precuneus. Overall, these results suggest that smoking expectancy is associated with increased activations in regions involved in action planning and reward valuation.
Finally, the ability to resist cigarette cravings was studied in four fMRI studies. Brody et al. (16) found that the PCC was engaged when participants were actively trying to suppress their urges, but not when they craved without trying to resist. Hartwell et al. (26) found that the ability to resist cigarette cravings was associated with increased activations in the left ACC, the ventro-/mPFC and the dlPFC. Zhao et al. (42) found that the inhibition of cue-induced cigarette cravings (via re-appraisal) was associated with increased activations of the right dorsal ACC. Finally, Kober et al. (43) showed that cognitive down-regulation of cigarette cravings was associated with increased activations in regions involved in cognitive control [e.g., the dlPFC, dmPFC, and ventro-lateral prefrontal cortex (vlPFC)]. It is therefore possible that smokers with poor self-control abilities experience greater difficulty in controlling their urges, and this is (partially) mediated by lower activation of fronto-cingulate regions. Such results highlight the importance of self-regulation abilities in the subjective experience of cigarette cravings.
Within-study heterogeneity
Attention has also been paid to the severity of smoking dependence and how it may influence brain cue reactivity. Apart from Vollstadt-Klein et al.’s (23) study, which found that severe smoking dependence was associated with decreased activations in the amygdala, hippocampus, putamen, and thalamus, most studies have shown that smoking dependence is positively associated with smoking cue-elicited brain activations. Thus far, severe smoking dependence has been associated with increased activations in craving-related frontal and temporal regions (44, 45), the insula (19, 44), and the (superior) parietal cortex (31, 45, 46). As such, these results suggest that cigarette cues provoke a stronger brain craving response in smokers whose dependence is more severe.
KEY CONCEPT 3. Brain cue reactivity
Relative to neutral stimuli, appetitive smoking-related cues have been shown to elicit significant activations within the extended visual cortex, the (medial and dorsolateral) prefrontal cortex, the (anterior and posterior) cingulate, the temporal cortex, the insula, and the dorsal striatum. The widespread brain reactivity to cigarette cues suggests that craving is a multidimensional construct.
In view of the clinical evidence showing that women and girls take less time to become dependent after initial use and have more difficulties quitting the habit (51, 52), preliminary studies examined the influence of sex-differences on the neural correlates of cigarette cravings. One of the factors contributing to these differences may be that women crave cigarettes more than men and that their desire to smoke is influenced by hormonal fluctuations across the menstrual cycle. Therefore, we performed a study involving tobacco-smoking men (n = 15) and women (n = 19) who underwent an fMRI session, during which neutral and smoking-related images, known to elicit craving, were presented (47). Women were tested twice; once during early follicular and once during mid-luteal phase of their menstrual cycle. The analysis did not reveal any significant sex differences in the cerebral activations associated with craving. This result contrasts with the fMRI findings from McClernon et al. (21), who found that women smokers exhibited larger cue reactivity in the right putamen, bilateral cuneus, and left middle temporal gyrus, while men had greater responses in the left hippocampus and left orbitofrontal cortex. Nevertheless, our study showed that brain activations in women varied across their menstrual cycle. More precisely, we found that female smokers had increased activations in the right angular/middle temporal gyrus in the follicular phase compared to the luteal phase. This latter result echoed the clinical reports of fluctuations in tobacco intake, withdrawal symptoms, and relapse rates across the menstrual cycle in women smokers (53, 54), as well as the preclinical findings showing that higher levels of estrogen (follicular phase) are associated with more reinforcing effects of addictive drugs, whereas higher levels of progesterone (luteal phase) are associated with less reinforcing effects (55).
Some authors have shown that one’s intention to quit can impact prefrontal and limbic activity toward cigarette pictures (48) Furthermore, it was shown that smokers who are dissatisfied with their smoking behavior, relative to those more accepting of their tobacco use, were more reactive (e.g., orbitofrontal and limbic activations) to appetitive cigarette cues (49).
Finally, genetic factors have also been shown to modulate brain reactivity to smoking cues. An association has been found between the dopamine transporter gene SLC6A3 polymorphism and ventral striatal and medial orbitofrontal activations in response to smoking cues (18), a finding that was subsequently replicated in another independent sample (19). In addition, an association has been observed between the nicotinic receptor alpha-5 subunit gene (rs16969968) polymorphism and smoking cue-elicited activations in the hippocampus and dorsal striatum (30).
Impulsivity
Personality traits, such as impulsivity, have been largely overlooked as potential factors contributing to heterogeneity in the fMRI studies on cigarette cravings. Impulsivity constitutes a key diagnostic criterion for several mental disorders, most importantly for antisocial personality disorder, borderline personality disorder, impulse-control disorders, and attention deficit and hyperactivity disorder (ADHD) (56, 57). Yet, the definition and dimensions of impulsivity remain a source of debate. The most widely accepted definition of impulsivity is a predisposition toward rapid, unplanned reactions to internal or external stimuli without regard for the negative consequences of these reactions for the impulsive individuals and others (58). There are (at least) five dimensions of impulsivity, namely: (i) the difficulty in maintaining one’s attention toward stimuli; (ii) the initiation of actions without forethought or planification; (iii) sensation/novelty seeking; (iv) the indifference toward the long-term consequences of one’s choices and actions; and (v) the preference of immediate over larger delayed rewards, regardless of its disadvantages (59–63). Several scales have been developed to measure the different components of impulsivity (60, 63, 64). Research using these scales has shown that impulsivity has the characteristics of a personality trait: it is relatively stable in time and genetically transmitted (65, 66).
Impulsivity has been extensively studied using cognitive tasks. Bari and Robbins (67) have recently proposed a model that defines two dimensions of impulsivity largely studied in cognitive science: (1) a rapid action form, which refers to behaviors that are performed without consideration for their consequences and (2) a slower form involving the adoption of desired behaviors despite their negative consequences [Note: other researchers have proposed similar models (68–70)]. Whereas the rapid form involves cognitive control processes allowing the flexible adaptation of behaviors to meet current demands (71, 72), the slower form entails value-based decision-making processes, which enable the selection of a behavior based on predicted positive or negative outcomes (73). While the rapid action form of impulsivity is assessed using response inhibition paradigms, such as the Go/No-Go task, which require the suppression of a pre-potent motor response (71, 74, 75), the slower form of impulsivity is assessed using risky decision-making tasks that include rewards, such as the Iowa Gambling task (76, 77). Other components of impulsivity, such as the ability to delay rewards (78–82), have been studied in cognitive science, but to a lesser extent. Moreover, delay-discounting tasks have been used less frequently than response inhibition and decision-making tasks in the functional imaging studies performed on the neural bases of impulsivity.
The neurobiology of impulsivity
Response inhibition and risky decision-making tasks have been largely employed to examine the neural bases of impulsivity, using functional imaging. Although there may be a partial overlap between the neural mechanisms underlying cognitive control and risky decision-making, the available evidence suggests that response inhibition tasks recruit a fronto-lateral executive network (74, 75, 83–85), while risky decision-making tasks recruit reward-related structures (86–88). Response inhibition tasks require withholding an already selected or initiated motor response. A recent meta-analysis of 30 fMRI studies (89) has shown that the vlPFC, the dlPFC, and the (dorsal) ACC are critically involved in response inhibition, presumably exerting executive control over the motor response. On the other hand, risky decision-making relies on mental processes that are mostly driven by reward seeking. A large-scale meta-analysis of 206 fMRI studies (90) has shown that rewards activate a valuation system composed of the ventro-medial PFC, the ventral ACC, and the (ventral) striatum. This is consistent with recent fMRI studies, highlighting the crucial role of these regions in risky decision-making (77, 91, 92). Thus, mounting evidence suggests that cognitive control involves fronto-lateral mechanisms (83), while risky decision-making relies on reward-related structures (70, 93).
Impulsivity and cigarette smoking
Impulsivity plays a critical role in the etiology of substance use disorders (94). In adolescents, impulsivity has repeatedly been shown to predict the onset of substance use and subsequent escalation of use (95, 96). In the case of tobacco, longitudinal studies have shown that impulsivity/hyperactivity traits at 12 years old predicted cigarette smoking 2 years later (97). In adolescents, it has also been shown that the preference for immediate rewards over larger delayed rewards promoted smoking acquisition (96). Likewise, an epidemiological study from Norway showed that impulsivity, as measured with the Barratt Impulsiveness Scale (BIS), was significantly associated with cigarette smoking initiation, even after controlling for education level (98).
Increased impulsivity levels have repeatedly been highlighted in chronic cigarette smokers, relative to non-smokers, using various clinical and cognitive instruments. Using the BIS, several studies have reported high levels of impulsivity traits in chronic cigarette smokers, relative to non-smokers (78, 81, 99–101). In addition, it has been shown, using the Go–No-go task, that compared to healthy volunteers, cigarette smokers fail more frequently to inhibit pre-potent motor responses (82, 99). Finally, it has been repeatedly demonstrated that cigarette smokers are less likely than non-smokers to choose large delayed rewards over small immediate ones in delay-discounting tasks (78–82). On neurobiological grounds, preliminary fMRI studies have shown that chronic smoking is associated with decreased ventral striatal activations during reward-related tasks (102, 103), and abnormal lateral prefrontal activations during the Stroop task (104).
In abstinent smokers, impulsivity has been shown to be a significant predictor of smoking relapse. In both adolescent and adult smokers receiving treatment for smoking cessation, smokers with impulsivity traits were found to be less likely to remain abstinent compared to non-impulsive smokers (105–107). Importantly, smokers who remained abstinent and those who relapsed did not differ at baseline in terms of number of smoked cigarettes, motivation to quit, confidence in their own abilities to quit, age, and sex. Similarly, Doran et al. (108) have shown, among smokers who relapsed during a 1-month intervention for smoking cessation, an association between impulsivity and shorter time to relapse. In order to explain the nature of the association between impulsivity and relapse, VanderVeen et al. (109, 110) hypothesized that during abstinence, the rewarding value of tobacco may be increased in impulsive smokers; that is, impulsive smokers may crave more for cigarettes during abstinence than non-impulsive ones.
Impulsivity and cigarette cravings
A growing number of studies have evidenced an association between impulsivity trait and cravings for alcohol (111–113), cocaine (114, 115), methamphetamine (115), and tobacco (116–118). Although the link between impulsivity and craving is increasingly substantiated by evidence, the mechanisms underlying this association remain poorly understood. Surprisingly, the neural mechanisms mediating the influence of impulsivity on cigarette cravings had not been studied (to our knowledge) until our research team sought to do so.
Impulsivity and the neural correlates of cigarette cravings
Impulsivity plays a pivotal role in the substance use onset, substance use relapse, and craving for psycho-active substances, including tobacco. Recently, our team performed an fMRI study seeking to examine the influence of trait impulsivity on the neural correlates of cue-elicited cigarette cravings (8). Thirty to 40 min prior to the scanning session, participants smoked a cigarette. While in the scanner, 31 chronic smokers viewed appetitive smoking-related and neutral images and reported their subjective craving levels. They also completed the BIS. The processing of appetitive smoking cues elicited, in smokers, activations in midline brain regions (the mPFC, ACC, and PCC) that have been repeatedly found to be activated in fMRI studies on tobacco cravings (6), and to be involved in self-referential processing (119–121). In addition, we observed a significant positive relationship between the total BIS score and subjective craving levels (r = 0.624; p < 0.001). Among second-order factors of the BIS (attentional, motor, and non-planning), it was the non-planning subscale that was the most significantly correlated with craving ratings (r = 0.625; p < 0.001). A negative correlation (r = −0.449; p = 0.015) was also observed between the total BIS score and activations in the PCC. Among second-order factors, only the non-planning subscale was significantly correlated with PCC activations (r = −0.440; p = 0.017). Such results were consistent with previous findings showing that the PCC is involved in resisting cigarette cravings (16). Based on the observed associations between impulsivity and PCC activations, we conducted functional connectivity analyses with the psycho-physiological interaction (PPI) method, using the PCC as the seed region. PPI analyses revealed significant negative coupling between the PCC and the dorsal ACC, the right dlPFC, and a region in the vicinity of the left insula. Thus, lower activations of the PCC, found in impulsive smokers, were associated with higher activations of brain regions involved in emotional (insula) and attentional (dACC and dlPFC) responses to smoking cues. Our findings highlighted the need for further investigations on the role of the PCC in drug addiction, as it is one of the most consistently activated regions in fMRI studies examining the neural correlates of cue-induced alcohol, drug, and tobacco cravings (6, 122, 123). Besides its role in self-referential processing, the PCC may be involved in the ability to resist cravings for psycho-active substances, including tobacco. Theoretically, an impaired functioning of the PCC may (indirectly) result in a lack of self-control over substance (tobacco) cravings. Although the PCC is not assumed to be a core cognitive control region, a neuro-imaging meta-analysis of 24 fMRI studies using stop-signal tasks recently showed that the PCC is one of the main activated regions during response inhibition (124).
Contrary to our expectations, we did not observe any direct relationship between impulsivity and dysfunctional activations in the dlPFC or the vlPFC (though the dlPFC emerged as significantly coupled with the PCC). Critically involved in cognitive control (74, 75, 89), these frontal regions have been shown to be implicated in efforts to inhibit cigarette cravings (26, 43). Although the reasons for these negative findings remain elusive, it is possible that the impulsivity trait refers to more complex neural processes than those involved in decision-making and cognitive control. Highly impulsive individuals are stimulus-bound and focus on immediate rather than long-term events. They also tend to lack introspection and have impaired mentalization abilities (125). Such characteristics are very unlikely to be captured by risky decision-making or response inhibition tasks. Over and above the dlPFC and vlPFC, the PCC is critical for self-relevant processes, such as mindfulness, mentalizing, and self-reflection (119–121). Altogether, these results should encourage researchers who will pursue future studies on the neurobiology of impulsivity in the addiction field to pay attention to components of impulsivity other than cognitive control and risky decision-making.
Future Perspectives: Tobacco Smoking in Psychiatric Disorders
Several psychiatric disorders are characterized by high or moderate levels of impulsivity, namely ADHD, bipolar, cluster-B personality, psychotic, and substance use disorders (7, 58, 126–129). Moreover, the prevalence of cigarette smoking is increased in patients with psychiatric disorders. In the US, approximately 29% of the population has a psychiatric disorder, and these individuals consume approximately 41% of the production of tobacco in the country (130). Although the prevalence of tobacco smoking has declined in the general population during the last decades, the consumption of tobacco products remained strikingly elevated in patients with schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder (PTSD), and ADHD, with prevalence estimates of 60–74, 66, 57, 40–86, and 40–42%, respectively (130–136). Elevated rates of tobacco smoking have also been observed in individuals with substance use disorders (137). It has been shown, indeed, that more than a third of patients with an alcohol use disorder and more than half of individuals who misuse (abuse/dependence) illicit drugs are also nicotine dependent (138). Therefore, psychiatric patients represent populations of interest for the study of the relationship between impulsivity and tobacco cravings, at both the behavioral and neural level.
Explanatory models
Two major hypotheses have been advanced to account for the elevated prevalence of tobacco smoking in psychiatric patients. The self-medication hypothesis proposes that psychiatric patients smoke cigarettes to relieve their psychiatric symptoms (anxiety, depression) or cognitive deficits (139). In support of this hypothesis, numerous studies have shown that the acute administration of nicotine (the main psycho-active agent of tobacco) to schizophrenia patients improves some of their cognitive deficits (e.g., attention, speed of processing, and working memory), and their impaired ability to filter out irrelevant information (140–142). Preliminary studies have shown that nicotine administration (or tobacco smoking) also improves cognitive performance in patients with ADHD (143, 144), bipolar disorder (145), and depression (20, 145).
Despite these findings, the self-medication hypothesis has been criticized over the years for its implied justification of tobacco smoking in psychiatric patients. Alternatively, the addiction vulnerability hypothesis proposes that neurobiological dysfunctions of the brain reward system, common to psychiatric and substance use disorders, make psychiatric patients more vulnerable to the rewarding effects of various psycho-active substances, including tobacco (139, 146, 147). In support of the addiction vulnerability hypothesis, several studies have shown that tobacco is more reinforcing for schizophrenia patients than it is for non-psychiatric smokers. Schizophrenia patients are more prone to smoke high-tar cigarettes, and they tend to smoke more cigarettes per day, extract more nicotine per cigarette, and have higher serum nicotine and cotinine (nicotine metabolite) levels compared to control smokers (148, 149). Preliminary evidence also suggests that cravings for cigarette are increased in schizophrenia patients (150, 151), 15 min or 72 h after smoking their last cigarette. Preliminary studies have shown that cigarette cravings are also elevated in other psychiatric disorders, including ADHD and PTSD (152–155). Despite these evidences, the neural correlates of tobacco cravings have been scarcely examined in psychiatric patients or individuals with psychiatric vulnerabilities (156–158).
Future studies will need to replicate and extend the findings demonstrating that cigarette cravings are increased in psychiatric patients, and to clarify whether bottom-up (e.g., motivational salience) or top-down (e.g., self-regulation) neural mechanisms explain these findings. To explore this self-regulation hypothesis, impulsivity will need to be measured in these populations. Although most studies in the comorbidity field have not focused on tobacco smoking specifically, mounting evidence shows that impulsivity is a key mediator of the association between substance use and psychiatric disorders, including ADHD, bipolar disorder, cluster-B personality disorders, and schizophrenia (7, 126–128). Several fMRI studies have examined the neural correlates of impulsivity in psychiatric patients (mostly bipolar disorder and schizophrenia) having no comorbid substance use disorders. Using various response inhibition tasks, these studies have shown that psychiatric patients have abnormal brain activations in regions involved in cognitive control, such as the dlPFC, the vlPFC, and/or the cingulate gyrus (159–163). Despite the variability in results, such findings pave the way to future neuro-imaging studies on drug (cigarette) cravings in psychiatric patients examining the interactions between cognitive control brain regions and those involved in craving experience.
KEY CONCEPT 4. Comorbidity
The prevalence of cigarette smoking is elevated in several psychiatric disorders characterized by high or moderate levels of impulsivity, namely attention deficit hyperactivity disorder, bipolar disorder, cluster-B personality disorders, psychotic disorders, and substance use disorders.
Conclusion
Given that craving is a core feature of tobacco use disorder and a significant predictor of smoking relapse, several fMRI studies have examined the neural correlates of (cue-induced) cigarette urges. The available literature has demonstrated that cigarette cravings elicit activations in regions involved in self-referential processing, planning/regulatory processes, emotional responding, attentional biases, and automatic conducts. Unfortunately, the implications of this literature are limited by the heterogeneity of results. Sources of heterogeneity include both methodological (abstinence, smoking expectancies, self-regulation) and individual factors (severity of smoking dependence, sex-differences, motivation to quit, genetic factors). Surprisingly, the potential influence of impulsivity has been largely ignored, although impulsivity is positively associated with cigarette cravings and smoking relapse. The influence of impulsivity on cigarette cravings is possibly mediated by fronto-cingulate mechanisms, as recently demonstrated by our team. Future behavioral and neuro-imaging studies will need to pay attention to the high prevalence of cigarette smoking in several psychiatric disorders, as these disorders are characterized by significant impulsivity.
Statements
Acknowledgments
SP is holder of the Eli Lilly Chair on Schizophrenia Research.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Stéphane Potvin is an associate research professor at the Department of Psychiatry from the University of Montreal, and is affiliated with the Centre de Recherche de l’Institut Universitaire en Santé Mentale de Montréal. Last year, he has been appointed as the holder of the Eli Lilly Chair on Schizophrenia Research. Dr Potvin has expertise on the schizophrenia-addiction comorbidity, which he has been studying using various neurocognitive methods, including functional magnetic resonance imaging.
References
1
World Health Organization. Report on the Global Tobacco Epidemic 2008. (2008). Available from: http://www.annals.edu.sg/PDF/37VolNo5May2008/V37N5p363.pdf
2
World Health Organization. The Smoker’s Body. (2004). Available from: http://www.who.int/tobacco/publications/health_effects/smokers_body/en/
3
World Health Organization. Tobacco. (2014). Available from: http://www.who.int/mediacentre/factsheets/fs339/en/
4
HughesJRPetersENNaudS. Relapse to smoking after 1 year of abstinence: a meta-analysis. Addict Behav (2008) 33(12):1516–20.10.1016/j.addbeh.2008.05.012
5
KillenJDFortmannSP. Craving is associated with smoking relapse: findings from three prospective studies. Exp Clin Psychopharmacol (1997) 5(2):137–42.10.1037/1064-1297.5.2.137
6
EngelmannJMVersaceFRobinsonJDMinnixJALamCYCuiYet alNeural substrates of smoking cue reactivity: a meta-analysis of fMRI studies. Neuroimage (2012) 60(1):252–62.10.1016/j.neuroimage.2011.12.024
7
JentschJDAshenhurstJRCervantesMCGromanSMJamesASPenningtonZT. Dissecting impulsivity and its relationships to drug addictions. Ann N Y Acad Sci (2014) 1327:1–26.10.1111/nyas.12388
8
BourqueJMendrekADinh-WilliamsLPotvinS. Neural circuitry of impulsivity in a cigarette craving paradigm. Front Psychiatry (2013) 4:67.10.3389/fpsyt.2013.00067
9
UssherMBeardEAbikoyeGHajekPWestR. Urge to smoke over 52 weeks of abstinence. Psychopharmacology (2013) 226(1):83–9.10.1007/s00213-012-2886-7
10
RobinsonTEBerridgeKC. The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res Brain Res Rev (1993) 18(3):247–91.10.1016/0165-0173(93)90013-P
11
TiffanySTConklinCA. A cognitive processing model of alcohol craving and compulsive alcohol use. Addiction (2000) 95(Suppl 2):S145–53.10.1046/j.1360-0443.95.8s2.3.x
12
HerdNBorlandRHylandA. Predictors of smoking relapse by duration of abstinence: findings from the international tobacco control (ITC) four country survey. Addiction (2009) 104(12):2088–99.10.1111/j.1360-0443.2009.02732.x
13
SweitzerMMDenlingerRLDonnyEC. Dependence and withdrawal-induced craving predict abstinence in an incentive-based model of smoking relapse. Nicotine Tob Res (2013) 15(1):36–43.10.1093/ntr/nts080
14
BediGPrestonKLEpsteinDHHeishmanSJMarroneGFShahamYet alIncubation of cue-induced cigarette craving during abstinence in human smokers. Biol Psychiatry (2011) 69(7):708–11.10.1016/j.biopsych.2010.07.014
15
ErblichJBoyarskyYSpringBNiauraRBovbjergDH. A family history of smoking predicts heightened levels of stress-induced cigarette craving. Addiction (2003) 98(5):657–64.10.1046/j.1360-0443.2003.00351.x
16
BrodyALMandelkernMAOlmsteadREJouJTiongsonEAllenVet alNeural substrates of resisting craving during cigarette cue exposure. Biol Psychiatry (2007) 62(6):642–51.10.1016/j.biopsych.2006.10.026
17
DavidSPMunafoMRJohansen-BergHSmithSMRogersRDMatthewsPMet alVentral striatum/nucleus accumbens activation to smoking-related pictorial cues in smokers and nonsmokers: a functional magnetic resonance imaging study. Biol Psychiatry (2005) 58(6):488–94.10.1016/j.biopsych.2005.04.028
18
FranklinTRLohoffFWWangZSciortinoNHarperDLiYet alDAT genotype modulates brain and behavioral responses elicited by cigarette cues. Neuropsychopharmacology (2009) 34(3):717–28.10.1038/npp.2008.124
19
FranklinTRWangZLiYSuhJJGoldmanMLohoffFWet alDopamine transporter genotype modulation of neural responses to smoking cues: confirmation in a new cohort. Addict Biol (2011) 16(2):308–22.10.1111/j.1369-1600.2010.00277.x
20
McClernonFJHiottFBWestmanECRoseJELevinED. Transdermal nicotine attenuates depression symptoms in nonsmokers: a double-blind, placebo-controlled trial. Psychopharmacology (2006) 189(1):125–33.10.1007/s00213-006-0516-y
21
McClernonFJKozinkRVRoseJE. Individual differences in nicotine dependence, withdrawal symptoms, and sex predict transient fMRI-BOLD responses to smoking cues. Neuropsychopharmacology (2008) 33(9):2148–57.10.1038/sj.npp.1301618
22
WilsonSJSayetteMADelgadoMRFiezJA. Instructed smoking expectancy modulates cue-elicited neural activity: a preliminary study. Nicotine Tob Res (2005) 7(4):637–45.10.1080/14622200500185520
23
Vollstadt-KleinSKobiellaABuhlerMGrafCFehrCMannKet alSeverity of dependence modulates smokers’ neuronal cue reactivity and cigarette craving elicited by tobacco advertisement. Addict Biol (2011) 16(1):166–75.10.1111/j.1369-1600.2010.00207.x
24
LeeJHLimYWiederholdBKGrahamSJ. A functional magnetic resonance imaging (FMRI) study of cue-induced smoking craving in virtual environments. Appl Psychophysiol Biofeedback (2005) 30(3):195–204.10.1007/s10484-005-6377-z
25
VersaceFEngelmannJMJacksonEFCostaVDRobinsonJDLamCYet alDo brain responses to emotional images and cigarette cues differ? An fMRI study in smokers. Eur J Neurosci (2011) 34(12):2054–63.10.1111/j.1460-9568.2011.07915.x
26
HartwellKJJohnsonKALiXMyrickHLeMattyTGeorgeMSet alNeural correlates of craving and resisting craving for tobacco in nicotine dependent smokers. Addict Biol (2011) 16(4):654–66.10.1111/j.1369-1600.2011.00340.x
27
McBrideDBarrettSPKellyJTAwADagherA. Effects of expectancy and abstinence on the neural response to smoking cues in cigarette smokers: an fMRI study. Neuropsychopharmacology (2006) 31(12):2728–38.10.1038/sj.npp.1301075
28
McClernonFJKozinkRVLutzAMRoseJE. 24-h smoking abstinence potentiates fMRI-BOLD activation to smoking cues in cerebral cortex and dorsal striatum. Psychopharmacology (2009) 204(1):25–35.10.1007/s00213-008-1436-9
29
KangOSChangDSJahngGHKimSYKimHKimJWet alIndividual differences in smoking-related cue reactivity in smokers: an eye-tracking and fMRI study. Prog Neuropsychopharmacol Biol Psychiatry (2012) 38(2):285–93.10.1016/j.pnpbp.2012.04.013
30
JanesACSmollerJWDavidSPFrederickBDHaddadSBasuAet alAssociation between CHRNA5 genetic variation at rs16969968 and brain reactivity to smoking images in nicotine dependent women. Drug Alcohol Depend (2012) 120(1–3):7–13.10.1016/j.drugalcdep.2011.06.009
31
YalachkovYKaiserJNaumerMJ. Brain regions related to tool use and action knowledge reflect nicotine dependence. J Neurosci (2009) 29(15):4922–9.10.1523/Jneurosci.4891-08.2009
32
WilsonSJSayetteMAFiezJA. Quitting-unmotivated and quitting-motivated cigarette smokers exhibit different patterns of cue-elicited brain activation when anticipating an opportunity to smoke. J Abnorm Psychol (2012) 121(1):198–211.10.1037/a0025112
33
TangDWFellowsLKSmallDMDagherA. Food and drug cues activate similar brain regions: a meta-analysis of functional MRI studies. Physiol Behav (2012) 106(3):317–24.10.1016/j.physbeh.2012.03.009
34
VolkowNDFowlerJSWangGJ. The addicted human brain viewed in the light of imaging studies: brain circuits and treatment strategies. Neuropharmacology (2004) 47(Suppl 1):3–13.10.1016/j.neuropharm.2004.07.019
35
Augustus DiggsHFroeligerBCarlsonJMGilbertDG. Smoker-nonsmoker differences in neural response to smoking-related and affective cues: an fMRI investigation. Psychiatry Res (2013) 211(1):85–7.10.1016/j.pscychresns.2012.06.009
36
VersaceFEngelmannJMRobinsonJDJacksonEFGreenCELamCYet alPrequit FMRI responses to pleasant cues and cigarette-related cues predict smoking cessation outcome. Nicotine Tob Res (2014) 16(6):697–708.10.1093/ntr/ntt214
37
Dinh-WilliamsLMendrekABourqueJPotvinS. Where there’s smoke, there’s fire: the brain reactivity of chronic smokers when exposed to the negative value of smoking. Prog Neuropsychopharmacol Biol Psychiatry (2014) 50:66–73.10.1016/j.pnpbp.2013.12.009
38
WakefieldMADurkinSSpittalMJSiahpushMScolloMSimpsonJAet alImpact of tobacco control policies and mass media campaigns on monthly adult smoking prevalence. Am J Public Health (2008) 98(8):1443–50.10.2105/AJPH.2007.128991
39
DavisKCFarrellyMCDukeJKellyLWillettJ. Antismoking media campaign and smoking cessation outcomes, New York State, 2003-2009. Prev Chronic Dis (2012) 9:110102.10.5888/pcd9.110102
40
WilsonSJSayetteMA. Neuroimaging craving: urge intensity matters. Addiction (2015) 110(2):195–203.10.1111/add.12676
41
HayashiTKoJHStrafellaAPDagherA. Dorsolateral prefrontal and orbitofrontal cortex interactions during self-control of cigarette craving. Proc Natl Acad Sci USA (2013) 110(11):4422–7.10.1073/pnas.1212185110
42
ZhaoLYTianJWangWQinWShiJLiQet alThe role of dorsal anterior cingulate cortex in the regulation of craving by reappraisal in smokers. PLoS One (2012) 7(8):e43598.10.1371/journal.pone.0043598
43
KoberHMende-SiedleckiPKrossEFWeberJMischelWHartCLet alPrefrontal-striatal pathway underlies cognitive regulation of craving. Proc Natl Acad Sci USA (2010) 107(33):14811–6.10.1073/pnas.1007779107
44
ClausEDBlaineSKFilbeyFMMayerARHutchisonKE. Association between nicotine dependence severity, BOLD response to smoking cues, and functional connectivity. Neuropsychopharmacology (2013) 38(12):2363–72.10.1038/npp.2013.134
45
GoudriaanAEde RuiterMBvan den BrinkWOosterlaanJVeltmanDJ. Brain activation patterns associated with cue reactivity and craving in abstinent problem gamblers, heavy smokers and healthy controls: an fMRI study. Addict Biol (2010) 15(4):491–503.10.1111/j.1369-1600.2010.00242.x
46
SmolkaMNBuhlerMKleinSZimmermannUMannKHeinzAet alSeverity of nicotine dependence modulates cue-induced brain activity in regions involved in motor preparation and imagery. Psychopharmacology (2006) 184(3–4):577–88.10.1007/s00213-005-0080-x
47
MendrekADinh-WilliamsLBourqueJPotvinS. Sex differences and menstrual cycle phase-dependent modulation of craving for cigarette: an FMRI pilot study. Psychiatry J (2014) 2014:723632.10.1155/2014/723632
48
WilsonSJSayetteMAFiezJA. Prefrontal responses to drug cues: a neurocognitive analysis. Nat Neurosci (2004) 7(3):211–4.10.1038/nn1200
49
StippekohlBWinklerMHWalterBKagererSMuchaRFPauliPet alNeural responses to smoking stimuli are influenced by smokers’ attitudes towards their own smoking behaviour. PLoS One (2012) 7(11):e46782.10.1371/journal.pone.0046782
50
MoellerSJGoldsteinRZ. Impaired self-awareness in human addiction: deficient attribution of personal relevance. Trends Cogn Sci (2014) 18(12):635–41.10.1016/j.tics.2014.09.003
51
Cepeda-BenitoAReynosoJTErathS. Meta-analysis of the efficacy of nicotine replacement therapy for smoking cessation: differences between men and women. J Consult Clin Psychol (2004) 72(4):712–22.10.1037/0022-006X.72.4.712
52
SieminskaAJassemE. The many faces of tobacco use among women. Med Sci Monit (2014) 20:153–62.10.12659/MSM.889796
53
SnivelyTAAhijevychKLBernhardLAWewersME. Smoking behavior, dysphoric states and the menstrual cycle: results from single smoking sessions and the natural environment. Psychoneuroendocrinology (2000) 25(7):677–91.10.1016/S0306-4530(00)00018-4
54
AllenAMMooneyMChakrabortyRAllenSS. Circadian patterns of ad libitum smoking by menstrual phase. Hum Psychopharmacol (2009) 24(6):503–6.10.1002/hup.1039
55
LynchWJSofuogluM. Role of progesterone in nicotine addiction: evidence from initiation to relapse. Exp Clin Psychopharmacol (2010) 18(6):451–61.10.1037/a0021265
56
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Washington, DC: American Psychiatric Publishing (2013).
57
World Health Organization. International Statistical Classification of Diseases and Related Health Problems – 10th Revision. Geneva: World Health Organization (2010).
58
MoellerFGBarrattESDoughertyDMSchmitzJMSwannAC. Psychiatric aspects of impulsivity. Am J Psychiatry (2001) 158(11):1783–93.10.1176/appi.ajp.158.11.1783
59
DalleyJWEverittBJRobbinsTW. Impulsivity, compulsivity, and top-down cognitive control. Neuron (2011) 69(4):680–94.10.1016/j.neuron.2011.01.020
60
PattonJHStanfordMSBarrattES. Factor structure of the Barratt impulsiveness scale. J Clin Psychol (1995) 51(6):768–74.10.1002/1097-4679(199511)51:6<768::AID-JCLP2270510607>3.0.CO;2-1
61
RobbinsTWGillanCMSmithDGde WitSErscheKD. Neurocognitive endophenotypes of impulsivity and compulsivity: towards dimensional psychiatry. Trends Cogn Sci (2012) 16(1):81–91.10.1016/j.tics.2011.11.009
62
StahlCVossASchmitzFNuszbaumMTuscherOLiebKet alBehavioral components of impulsivity. J Exp Psychol Gen (2014) 143(2):850–86.10.1037/a0033981
63
WhitesideSPLynamDR. The five factor model and impulsivity: using a structural model of personality to understand impulsivity. Pers Individ Dif (2001) 30(4):669–89.10.1016/S0191-8869(00)00064-7
64
EysenckSBGPearsonPREastingGAllsoppJF. Age norms for impulsiveness, venturesomeness and empathy in adults. Pers Individ Dif (1985) 6(5):613–9.10.1016/0191-8869(85)90011-X
65
EysenckHJ. The nature of impulsivity. In: McCownWGJohnsonJLShureMB editors. The Impulsive Client: Theory, Research, and Treatment. Washington, DC: American Psychological Association (1993). p. 57–69.
66
CloningerCRPrzybeckTRSvrakicDM. The tridimensional personality questionnaire: U.S. normative data. Psychol Rep (1991) 69(3 Pt 1):1047–57.10.2466/PR0.69.7.1047-1057
67
BariARobbinsTW. Inhibition and impulsivity: behavioral and neural basis of response control. Prog Neurobiol (2013) 108:44–79.10.1016/j.pneurobio.2013.06.005
68
JuppBDalleyJW. Convergent pharmacological mechanisms in impulsivity and addiction: insights from rodent models. Br J Pharmacol (2014) 171(20):4729–66.10.1111/Bph.12787
69
JuppBDalleyJW. Behavioral endophenotypes of drug addiction: etiological insights from neuroimaging studies. Neuropharmacology (2014) 76(Pt B):487–97.10.1016/j.neuropharm.2013.05.041
70
GlascherJAdolphsRDamasioHBecharaARudraufDCalamiaMet alLesion mapping of cognitive control and value-based decision making in the prefrontal cortex. Proc Natl Acad Sci USA (2012) 109(36):14681–6.10.1073/pnas.1206608109
71
BarchDMBraverTSCarterCSPoldrackRARobbinsTW. CNTRICS final task selection: executive control. Schizophr Bull (2009) 35(1):115–35.10.1093/schbul/sbn154
72
BotvinickMMBraverTSBarchDMCarterCSCohenJD. Conflict monitoring and cognitive control. Psychol Rev (2001) 108(3):624–52.10.1037/0033-295X.108.3.624
73
GutnikLAHakimzadaAFYoskowitzNAPatelVL. The role of emotion in decision-making: a cognitive neuroeconomic approach towards understanding sexual risk behavior. J Biomed Inform (2006) 39(6):720–36.10.1016/j.jbi.2006.03.002
74
RubiaKSmithATaylorE. Performance of children with attention deficit hyperactivity disorder (ADHD) on a test battery of impulsiveness. Child Neuropsychol (2007) 13(3):276–304.10.1080/09297040600770761
75
RubiaKSmithABWoolleyJNosartiCHeymanITaylorEet alProgressive increase of frontostriatal brain activation from childhood to adulthood during event-related tasks of cognitive control. Hum Brain Mapp (2006) 27(12):973–93.10.1002/hbm.20237
76
BecharaADamasioHDamasioAR. Emotion, decision making and the orbitofrontal cortex. Cereb Cortex (2000) 10(3):295–307.10.1093/cercor/10.3.295
77
BoggTFukunagaRFinnPRBrownJW. Cognitive control links alcohol use, trait disinhibition, and reduced cognitive capacity: evidence for medial prefrontal cortex dysregulation during reward-seeking behavior. Drug Alcohol Depend (2012) 122(1–2):112–8.10.1016/j.drugalcdep.2011.09.018
78
FieldsSCollinsCLeraasKReynoldsB. Dimensions of impulsive behavior in adolescent smokers and nonsmokers. Exp Clin Psychopharmacol (2009) 17(5):302–11.10.1037/a0017185
79
ReynoldsBRichardsJBHornKKarrakerK. Delay discounting and probability discounting as related to cigarette smoking status in adults. Behav Processes (2004) 65(1):35–42.10.1016/S0376-6357(03)00109-8
80
PetersJBrombergUSchneiderSBrassenSMenzMBanaschewskiTet alLower ventral striatal activation during reward anticipation in adolescent smokers. Am J Psychiatry (2011) 168(5):540–9.10.1176/appi.ajp.2010.10071024
81
MitchellSH. Measures of impulsivity in cigarette smokers and non-smokers. Psychopharmacology (1999) 146(4):455–64.10.1007/PL00005491
82
MitchellSH. Measuring impulsivity and modeling its association with cigarette smoking. Behav Cogn Neurosci Rev (2004) 3(4):261–75.10.1177/1534582305276838
83
Castellanos-RyanNRubiaKConrodPJ. Response inhibition and reward response bias mediate the predictive relationships between impulsivity and sensation seeking and common and unique variance in conduct disorder and substance misuse. Alcohol Clin Exp Res (2011) 35(1):140–55.10.1111/j.1530-0277.2010.01331.x
84
GaravanHHesterRMurphyKFassbenderCKellyC. Individual differences in the functional neuroanatomy of inhibitory control. Brain Res (2006) 1105(1):130–42.10.1016/j.brainres.2006.03.029
85
MenonVAdlemanNEWhiteCDGloverGHReissAL. Error-related brain activation during a Go/NoGo response inhibition task. Hum Brain Mapp (2001) 12(3):131–43.10.1002/1097-0193(200103)12:3<131::AID-HBM1010>3.0.CO;2-C
86
ChengGLTangJCLiFWLauEYLeeTM. Schizophrenia and risk-taking: impaired reward but preserved punishment processing. Schizophr Res (2012) 136(1–3):122–7.10.1016/j.schres.2012.01.002
87
KringelbachMLRollsET. The functional neuroanatomy of the human orbitofrontal cortex: evidence from neuroimaging and neuropsychology. Prog Neurobiol (2004) 72(5):341–72.10.1016/j.pneurobio.2004.03.006
88
Van LeijenhorstLMoorBGOp de MacksZARomboutsSARBWestenbergPMCroneEA. Adolescent risky decision-making: neurocognitive development of reward and control regions. Neuroimage (2010) 51(1):345–55.10.1016/j.neuroimage.2010.02.038
89
CriaudMBoulinguezP. Have we been asking the right questions when assessing response inhibition in go/no-go tasks with fMRI? A meta-analysis and critical review. Neurosci Biobehav Rev (2013) 37(1):11–23.10.1016/j.neubiorev.2012.11.003
90
BartraOMcGuireJTKableJW. The valuation system: a coordinate-based meta-analysis of BOLD fMRI experiments examining neural correlates of subjective value. Neuroimage (2013) 76:412–27.10.1016/j.neuroimage.2013.02.063
91
RaoHMamikonyanEDetreJASiderowfADSternMBPotenzaMNet alDecreased ventral striatal activity with impulse control disorders in Parkinson’s disease. Mov Disord (2010) 25(11):1660–9.10.1002/mds.23147
92
SchonbergTFoxCRMumfordJACongdonETrepelCPoldrackRA. Decreasing ventromedial prefrontal cortex activity during sequential risk-taking: an fMRI investigation of the balloon analogue risk task. Front Neurosci (2012) 6:80.10.3389/fnins.2012.00080
93
NoonanMPWaltonMEBehrensTESalletJBuckleyMJRushworthMF. Separate value comparison and learning mechanisms in macaque medial and lateral orbitofrontal cortex. Proc Natl Acad Sci USA (2010) 107(47):20547–52.10.1073/pnas.1012246107
94
WillsTAVaccaroDMcNamaraG. Novelty seeking, risk taking, and related constructs as predictors of adolescent substance use: an application of Cloninger’s theory. J Subst Abuse (1994) 6(1):1–20.10.1016/S0899-3289(94)90039-6
95
ErnstMLuckenbaughDAMoolchanETLeffMKAllenREshelNet alBehavioral predictors of substance-use initiation in adolescents with and without attention-deficit/hyperactivity disorder. Pediatrics (2006) 117(6):2030–9.10.1542/peds.2005-0704
96
Audrain-McGovernJRodriguezDEpsteinLHCuevasJRodgersKWileytoEP. Does delay discounting play an etiological role in smoking or is it a consequence of smoking?Drug Alcohol Depend (2009) 103(3):99–106.10.1016/j.drugalcdep.2008.12.019
97
KorhonenTLevalahtiEDickDMPulkkinenLRoseRJKaprioJet alExternalizing behaviors and cigarette smoking as predictors for use of illicit drugs: a longitudinal study among Finnish adolescent twins. Twin Res Hum Genet (2010) 13(6):550–8.10.1375/twin.13.6.550
98
KvaavikERiseJ. How do impulsivity and education relate to smoking initiation and cessation among young adults?J Stud Alcohol Drugs (2012) 73(5):804–10.10.15288/jsad.2012.73.804
99
SpinellaM. Correlations between orbitofrontal dysfunction and tobacco smoking. Addict Biol (2002) 7(4):381–4.10.1080/1355621021000005964
100
FloryJDManuckSB. Impulsiveness and cigarette smoking. Psychosom Med (2009) 71(4):431–7.10.1097/PSY.0b013e3181988c2d
101
BalevichECWeinNDFloryJD. Cigarette smoking and measures of impulsivity in a college sample. Subst Abus (2013) 34(3):256–62.10.1080/08897077.2012.763082
102
KobiellaARipkeSKroemerNBVollmertCVollstadt-KleinSUlshoferDEet alAcute and chronic nicotine effects on behaviour and brain activation during intertemporal decision making. Addict Biol (2014) 19(5):918–30.10.1111/adb.12057
103
LuoSAinslieGGiragosianLMonterossoJR. Striatal hyposensitivity to delayed rewards among cigarette smokers. Drug Alcohol Depend (2011) 116(1–3):18–23.10.1016/j.drugalcdep.2010.11.012
104
XuJMendrekACohenMSMonterossoJSimonSJarvikMet alEffect of cigarette smoking on prefrontal cortical function in nondeprived smokers performing the stroop task. Neuropsychopharmacology (2007) 32(6):1421–8.10.1038/sj.npp.1301272
105
WegmannLBuhlerAStrunkMLangPNowakD. Smoking cessation with teenagers: the relationship between impulsivity, emotional problems, program retention and effectiveness. Addict Behav (2012) 37(4):463–8.10.1016/j.addbeh.2011.12.008
106
Krishnan-SarinSReynoldsBDuhigAMSmithALissTMcFetridgeAet alBehavioral impulsivity predicts treatment outcome in a smoking cessation program for adolescent smokers. Drug Alcohol Depend (2007) 88(1):79–82.10.1016/j.drugalcdep.2006.09.006
107
ShefferCMackillopJMcGearyJLandesRCarterLYiRet alDelay discounting, locus of control, and cognitive impulsiveness independently predict tobacco dependence treatment outcomes in a highly dependent, lower socioeconomic group of smokers. Am J Addict (2012) 21(3):221–32.10.1111/j.1521-0391.2012.00224.x
108
DoranNSpringBMcChargueDPergadiaMRichmondM. Impulsivity and smoking relapse. Nicotine Tob Res (2004) 6(4):641–7.10.1080/14622200410001727939
109
VanderVeenJWCohenLMCukrowiczKCTrotterDR. The role of impulsivity on smoking maintenance. Nicotine Tob Res (2008) 10(8):1397–404.10.1080/14622200802239330
110
VanderVeenJWCohenLMTrotterDRMCollinsFL. Impulsivity and the role of smoking-related outcome expectancies among dependent college-aged cigarette smokers. Addict Behav (2008) 33(8):1006–11.10.1016/j.addbeh.2008.03.007
111
PapachristouHNederkoornCHavermansRvan der HorstMJansenA. Can’t stop the craving: the effect of impulsivity on cue-elicited craving for alcohol in heavy and light social drinkers. Psychopharmacology (2012) 219(2):511–8.10.1007/s00213-011-2240-5
112
PapachristouHNederkoornCHavermansRBongersPBeunenSJansenA. Higher levels of trait impulsiveness and a less effective response inhibition are linked to more intense cue-elicited craving for alcohol in alcohol-dependent patients. Psychopharmacology (Berl) (2013) 228(4):641–9.10.1007/s00213-013-3063-3
113
JoosLGoudriaanAESchmaalLDe WitteNAVan den BrinkWSabbeBGet alThe relationship between impulsivity and craving in alcohol dependent patients. Psychopharmacology (2013) 226(2):273–83.10.1007/s00213-012-2905-8
114
RoozenHGvan der KroftPvan MarleHJFrankenIH. The impact of craving and impulsivity on aggression in detoxified cocaine-dependent patients. J Subst Abuse Treat (2011) 40(4):414–8.10.1016/j.jsat.2010.12.003
115
TziortzisDMahoneyJJIIIKalechsteinADNewtonTFDe la GarzaRII. The relationship between impulsivity and craving in cocaine- and methamphetamine-dependent volunteers. Pharmacol Biochem Behav (2011) 98(2):196–202.10.1016/j.pbb.2010.12.022
116
DoranNSpringBMcChargueD. Effect of impulsivity on craving and behavioral reactivity to smoking cues. Psychopharmacology (2007) 194(2):279–88.10.1007/s00213-007-0832-x
117
DoranNCookJMcChargueDSpringB. Impulsivity and cigarette craving: differences across subtypes. Psychopharmacology (2009) 207(3):365–73.10.1007/s00213-009-1661-x
118
BillieuxJVan der LindenMCeschiG. Which dimensions of impulsivity are related to cigarette craving?Addict Behav (2007) 32(6):1189–99.10.1016/j.addbeh.2006.08.007
119
FranssonPMarrelecG. The precuneus/posterior cingulate cortex plays a pivotal role in the default mode network: evidence from a partial correlation network analysis. Neuroimage (2008) 42(3):1178–84.10.1016/j.neuroimage.2008.05.059
120
QinPNorthoffG. How is our self related to midline regions and the default-mode network?Neuroimage (2011) 57(3):1221–33.10.1016/j.neuroimage.2011.05.028
121
Shaurya PrakashRDe LeonAAKlattMMalarkeyWPattersonB. Mindfulness disposition and default-mode network connectivity in older adults. Soc Cogn Affect Neurosci (2013) 8(1):112–7.10.1093/scan/nss115
122
PotenzaMNHongKILacadieCMFulbrightRKTuitKLSinhaR. Neural correlates of stress-induced and cue-induced drug craving: influences of sex and cocaine dependence. Am J Psychiatry (2012) 169(4):406–14.10.1176/appi.ajp.2011.11020289
123
SchachtJPAntonRFMyrickH. Functional neuroimaging studies of alcohol cue reactivity: a quantitative meta-analysis and systematic review. Addict Biol (2013) 18(1):121–33.10.1111/j.1369-1600.2012.00464.x
124
CieslikECMuellerVIEickhoffCRLangnerREickhoffSB. Three key regions for supervisory attentional control: evidence from neuroimaging meta-analyses. Neurosci Biobehav Rev (2015) 48:22–34.10.1016/j.neubiorev.2014.11.003
125
BatemanAFonagyP. Mentalization based treatment for borderline personality disorder. World Psychiatry (2010) 9(1):11–5. 10.1002/j.2051-5545.2010.tb00255.x
126
BornovalovaMALejuezCWDaughtersSBRosenthalMZLynchTR. Impulsivity as a common process across borderline personality and substance use disorders. Clin Psychol Rev (2005) 25(6):790–812.10.1016/j.cpr.2005.05.005
127
SwannAC. The strong relationship between bipolar and substance-use disorder mechanisms and treatment implications. Ann N Y Acad Sci (2010) 1187:276–93.10.1111/j.1749-6632.2009.05146.x
128
ZhornitskySRizkallahEPampoulovaTChiassonJPLippOStipEet alSensation-seeking, social anhedonia, and impulsivity in substance use disorder patients with and without schizophrenia and in non-abusing schizophrenia patients. Psychiatry Res (2012) 200(2–3):237–41.10.1016/j.psychres.2012.07.046
129
OuzirM. Impulsivity in schizophrenia: a comprehensive update. Aggress Violent Behav (2013) 18(2):247–54.10.1016/j.avb.2012.11.014
130
LasserKBoydJWWoolhandlerSHimmelsteinDUMcCormickDBorDH. Smoking and mental illness: a population-based prevalence study. JAMA (2000) 284(20):2606–10.10.1001/jama.284.20.2606
131
ChapmanSRaggMMcGeechanK. Citation bias in reported smoking prevalence in people with schizophrenia. Aust N Z J Psychiatry (2009) 43(3):277–82.10.1080/00048670802653372
132
de LeonJDiazFJ. A meta-analysis of worldwide studies demonstrates an association between schizophrenia and tobacco smoking behaviors. Schizophr Res (2005) 76(2–3):135–57.10.1016/j.schres.2005.02.010
133
LambertNMHartsoughCS. Prospective study of tobacco smoking and substance dependencies among samples of ADHD and non-ADHD participants. J Learn Disabil (1998) 31(6):533–44.10.1177/002221949803100603
134
PomerleauOFDowneyKKStelsonFWPomerleauCS. Cigarette smoking in adult patients diagnosed with attention deficit hyperactivity disorder. J Subst Abuse (1995) 7(3):373–8.10.1016/0899-3289(95)90030-6
135
DiazFJJamesDBottsSMawLSusceMTde LeonJ. Tobacco smoking behaviors in bipolar disorder: a comparison of the general population, schizophrenia, and major depression. Bipolar Disord (2009) 11(2):154–65.10.1111/j.1399-5618.2009.00664.x
136
FuSSMcFallMSaxonAJBeckhamJCCarmodyTPBakerDGet alPost-traumatic stress disorder and smoking: a systematic review. Nicotine Tob Res (2007) 9(11):1071–84.10.1080/14622200701488418
137
OpaleyeESSanchezZMMouraYGGaldurozJCLocatelliDPNotoAR. The Brazilian smoker: a survey in the largest cities of Brazil. Rev Bras Psiquiatr (2012) 34(1):43–51.10.1016/S1516-4446(12)70009-0
138
GrantBFHasinDSChouSPStinsonFSDawsonDA. Nicotine dependence and psychiatric disorders in the United States: results from the national epidemiologic survey on alcohol and related conditions. Arch Gen Psychiatry (2004) 61(11):1107–15.10.1001/archpsyc.61.12.1226
139
WingVCMossTGRabinRAGeorgeTP. Effects of cigarette smoking status on delay discounting in schizophrenia and healthy controls. Addict Behav (2012) 37(1):67–72.10.1016/j.addbeh.2011.08.012
140
MackowickKMBarrMSWingVCRabinRAOuellet-PlamondonCGeorgeTP. Neurocognitive endophenotypes in schizophrenia: modulation by nicotinic receptor systems. Prog Neuropsychopharmacol Biol Psychiatry (2014) 52:79–85.10.1016/j.pnpbp.2013.07.010
141
SaccoKATermineASeyalADudasMMVessicchioJCKrishnan-SarinSet alEffects of cigarette smoking on spatial working memory and attentional deficits in schizophrenia: involvement of nicotinic receptor mechanisms. Arch Gen Psychiatry (2005) 62(6):649–59.10.1001/archpsyc.62.6.649
142
SmithRCWarner-CohenJMatuteMButlerEKellyEVaidhyanathaswamySet alEffects of nicotine nasal spray on cognitive function in schizophrenia. Neuropsychopharmacology (2006) 31(3):637–43.10.1038/sj.npp.1300881
143
PotterASNewhousePA. Acute nicotine improves cognitive deficits in young adults with attention-deficit/hyperactivity disorder. Pharmacol Biochem Behav (2008) 88(4):407–17.10.1016/j.pbb.2007.09.014
144
WilensTEDeckerMW. Neuronal nicotinic receptor agonists for the treatment of attention-deficit/hyperactivity disorder: focus on cognition. Biochem Pharmacol (2007) 74(8):1212–23.10.1016/j.bcp.2007.07.002
145
CaldirolaDDaccoSGrassiMCitterioAMenottiRCavediniPet alEffects of cigarette smoking on neuropsychological performance in mood disorders: a comparison between smoking and nonsmoking inpatients. J Clin Psychiatry (2013) 74(2):E130–6.10.4088/Jcp.12m07985
146
PotvinSStipERoyJY. [Schizophrenia and addiction: an evaluation of the self-medication hypothesis]. Encephale (2003) 29(3 Pt 1):193–203.
147
KrystalJHD’SouzaDCGallinatJDriesenNAbi-DarghamAPetrakisIet alThe vulnerability to alcohol and substance abuse in individuals diagnosed with schizophrenia. Neurotox Res (2006) 10(3–4):235–52.10.1007/BF03033360
148
WilliamsJMGandhiKKLuSEKumarSShenJFouldsJet alHigher nicotine levels in schizophrenia compared with controls after smoking a single cigarette. Nicotine Tob Res (2010) 12(8):855–9.10.1093/ntr/ntq102
149
WilliamsJMZiedonisDMAbanyieFSteinbergMLFouldsJBenowitzNL. Increased nicotine and cotinine levels in smokers with schizophrenia and schizoaffective disorder is not a metabolic effect. Schizophr Res (2005) 79(2–3):323–35.10.1016/j.schres.2005.04.016
150
LoSHeishmanSJRaleyHWrightKWehringHJMoolchanETet alTobacco craving in smokers with and without schizophrenia. Schizophr Res (2011) 127(1–3):241–5.10.1016/j.schres.2010.06.017
151
TideyJWColbySMXavierEMH. Effects of smoking abstinence on cigarette craving, nicotine withdrawal, and nicotine reinforcement in smokers with and without schizophrenia. Nicotine Tob Res (2014) 16(3):326–34.10.1093/Ntr/Ntt152
152
BerlinIHuMCCoveyLSWinhusenT. Attention-deficit/hyperactivity disorder (ADHD) symptoms, craving to smoke, and tobacco withdrawal symptoms in adult smokers with ADHD. Drug Alcohol Depend (2012) 124(3):268–73.10.1016/j.drugalcdep.2012.01.019
153
KollinsSHEnglishJSRoleyMEO’BrienBBlairJLaneSDet alEffects of smoking abstinence on smoking-reinforced responding, withdrawal, and cognition in adults with and without attention deficit hyperactivity disorder. Psychopharmacology (2013) 227(1):19–30.10.1007/s00213-012-2937-0
154
BeckhamJCDennisMFMcClernonFJMozleySLCollieCFVranaSR. The effects of cigarette smoking on script-driven imagery in smokers with and without posttraumatic stress disorder. Addict Behav (2007) 32(12):2900–15.10.1016/j.addbeh.2007.04.026
155
DedertEACalhounPSHarperLADuttonCEMcClernonFJBeckhamJC. Smoking withdrawal in smokers with and without posttraumatic stress disorder. Nicotine Tob Res (2012) 14(3):372–6.10.1093/Ntr/Ntr142
156
PotvinSLunguOLippOLalondePMelunJMendrekA. Craving for irrelevant stimuli in schizophrenia smokers: an fMRI study. Biol Psychiatry (2015) 77(9): 356S–357S.
157
CourtneyKEGhahremaniDGLondonEDRayLA. The association between cue-reactivity in the precuneus and level of dependence on nicotine and alcohol. Drug Alcohol Depend (2014) 141:21–6.10.1016/j.drugalcdep.2014.04.026
158
KingAMcNamaraPAngstadtMPhanKL. Neural substrates of alcohol-induced smoking urge in heavy drinking nondaily smokers. Neuropsychopharmacology (2010) 35(3):692–701.10.1038/npp.2009.177
159
HajekTAldaMHajekEIvanoffJ. Functional neuroanatomy of response inhibition in bipolar disorders – combined voxel based and cognitive performance meta-analysis. J Psychiatr Res (2013) 47(12):1955–66.10.1016/j.jpsychires.2013.08.015
160
JacobGAZvonikKKamphausenSSebastianAMaierSPhilipsenAet alEmotional modulation of motor response inhibition in women with borderline personality disorder: an fMRI study. J Psychiatry Neurosci (2013) 38(3):164–72.10.1503/jpn.120029
161
VollmBRichardsonPMcKieSReniersRElliottRAndersonIMet alNeuronal correlates and serotonergic modulation of behavioural inhibition and reward in healthy and antisocial individuals. J Psychiatr Res (2010) 44(3):123–31.10.1016/j.jpsychires.2009.07.005
162
SambataroFMattayVSThurinKSafrinMRasettiRBlasiGet alAltered cerebral response during cognitive control: a potential indicator of genetic liability for schizophrenia. Neuropsychopharmacology (2013) 38(5):846–53.10.1038/npp.2012.250
163
VercammenAMorrisRGreenMJLenrootRKulkarniJCarrVJet alReduced neural activity of the prefrontal cognitive control circuitry during response inhibition to negative words in people with schizophrenia. J Psychiatry Neurosci (2012) 37(6):379–88.10.1503/jpn.110088
Summary
Keywords
cigarette, cravings, fMRI, individual differences, impulsivity
Citation
Potvin S, Tikàsz A, Dinh-Williams LL-A, Bourque J and Mendrek A (2015) Cigarette Cravings, Impulsivity, and the Brain. Front. Psychiatry 6:125. doi: 10.3389/fpsyt.2015.00125
Received
29 March 2015
Accepted
26 August 2015
Published
08 September 2015
Volume
6 - 2015
Edited by
Alain Dervaux, Centre Hospitalier Sainte-Anne, France
Reviewed by
Peter G. Enticott, Deakin University, Australia; Brett Froeliger, Medical University of South Carolina, USA
Updates
Copyright
© 2015 Potvin, Tikàsz, Dinh-Williams, Bourque and Mendrek.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: stephane.potvin@umontreal.ca
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.