Disinhibition over drug use, enhanced salience of drug use and decreased salience of natural reinforcers are thought to play an important role substance dependence. Whether this is also true for pathological gambling is unclear. To understand the effects of affective stimuli on response inhibition in problem gamblers (PRGs), we designed an affective Go/Nogo to examine the interaction between response inhibition and salience attribution in 16 PRGs and 15 healthy controls (HCs).
Four affective blocks were presented with Go trials containing neutral, gamble, positive or negative affective pictures. The No-Go trials in these blocks contained neutral pictures. Outcomes of interest included percentage of impulsive errors and mean reaction times in the different blocks. Brain activity related to No-Go trials was assessed to measure response inhibition in the various affective conditions and brain activity related to Go trials was assessed to measure salience attribution.
PRGs made fewer errors during gamble and positive trials than HCs, but were slower during all trials types. Compared to HCs, PRGs activated the dorsolateral prefrontal cortex, anterior cingulate and ventral striatum to a greater extent while viewing gamble pictures. The dorsal lateral and inferior frontal cortex were more activated in PRGs than in HCs while viewing positive and negative pictures. During neutral inhibition, PRGs were slower but similar in accuracy to HCs, and showed more dorsolateral prefrontal and anterior cingulate cortex activity. In contrast, during gamble and positive pictures PRGs performed better than HCs, and showed lower activation of the dorsolateral and anterior cingulate cortex.
This study shows that gambling-related stimuli are more salient for PRGs than for HCs. PRGs seem to rely on compensatory brain activity to achieve similar performance during neutral response inhibition. A gambling-related or positive context appears to facilitate response inhibition as indicated by lower brain activity and fewer behavioural errors in PRGs.
There is a wealth of evidence showing enhanced attention towards drug-related information (i.e. attentional bias) in substance abusers. However, little is known about attentional bias in deregulated behaviors without substance use such as abnormal gambling. This study examined whether problem gamblers (PrG, as assessed through self-reported gambling-related craving and gambling dependence severity) exhibit attentional bias for gambling-related cues.
Forty PrG and 35 control participants performed a change detection task using the flicker paradigm, in which two images differing in only one aspect are repeatedly flashed on the screen until the participant is able to report the changing item. In our study, the changing item was either neutral or related to gambling. Eye movements were recorded, which made it possible to measure both initial orienting of attention as well as its maintenance on gambling information.
Direct (eye-movements) and indirect (change in detection latency) measures of attention in individuals with problematic gambling behaviors suggested the occurrence of both engagement and of maintenance attentional biases towards gambling-related visual cues. Compared to non-problematic gamblers, PrG exhibited (1) faster reaction times to gambling-cues as compared to neutral cues, (2) higher percentage of initial saccades directed toward gambling pictures; (3) an increased fixation duration and fixation count on gambling pictures. In the PrG group, measures of gambling-related attentional bias were not associated with craving for gambling and gambling dependence severity. Theoretical and clinical implications of these results are discussed.
Gambling; Attentional bias; Dependence; Eye-tracking; Craving
Motivational and cognitive abnormalities are frequently reported in pathological gambling. However, studies simultaneously investigating motivational and cognitive processing in problematic gamblers are lacking, limiting our understanding of the interplay between these systems in problematic gambling. Studies in non-clinical samples indicate that interactions between dorsal “executive” and ventral “affective” processing systems are necessary for adequate responses in various emotive situations.
We conducted a generalized Psycho-Physiological Interaction (gPPI) analysis to assess the influence of affective stimuli on changes in functional connectivity associated with response inhibition in 16 treatment seeking problematic gamblers (PRGs) and 15 healthy controls (HCs) using an affective Go-NoGo fMRI paradigm including neutral, gambling-related, positive and negative pictures as neutral and affective conditions.
Across groups, task performance accuracy during neutral inhibition trials was positively correlated with functional connectivity between the left caudate and the right middle frontal cortex. During inhibition in the gambling condition, only in PRGs accuracy of task performance was positively correlated with functional connectivity within sub-regions of the dorsal executive system. Group interactions showed that during neutral inhibition, HCs exhibited greater functional connectivity between the left caudate and occipital cortex than PRGs. In contrast, during inhibition in the positive condition, PRGs compared to HCs showed greater functional connectivity between the left caudate and occipital cortex. During inhibition trials in the negative condition, a stronger functional connectivity between the left caudate and the right anterior cingulate cortex in PRGs compared to HCs was present. There were no group interactions during inhibition in the gambling condition.
During gamble inhibition PRGs seem to benefit more from functional connectivity within the dorsal executive system than HCs, because task accuracy in this condition in PRGs is positively correlated with functional connectivity, although the groups show similar connectivity patterns during gamble inhibition. Greater functional connectivity between the ventral affective system and the dorsal executive system in PRGs in the affective conditions compared to HCs, suggests facilitation of the dorsal executive system when affective stimuli are present specifically in PRGs.
Twenty-one treatment-seeking pathological gamblers, 21 pathological gamblers in recovery, and 21 recreational gamblers watched two video-taped exciting gambling scenarios and an exciting roller-coaster control scenario while their arousal (heart rate and subjective excitement) and urge to gamble were being measured. The gamblers did not differ significantly in cue-elicited heart rate elevations or excitement. However, the active pathological gamblers reported significantly greater urges to gamble across all cues compared to the abstinent pathological gamblers and, with marginal significance (p = 0.06), also compared to the social gamblers. Further exploration of these findings revealed that active pathological gamblers experience urges to gamble in response to exciting situations, whether or not they are gambling related, whereas abstinent and social gamblers only report urges to an exciting gambling-related cue. This suggests that for pathological gamblers excitement itself, irrespective of its source, may become a conditioned stimulus capable of triggering gambling behavior. Implications for treatment and future research are discussed.
Pathological gambling; Cue reactivity; Urge; Excitement; Addiction
To achieve greater understanding of the brain mechanisms underlying nicotine craving in female smokers, we examined the influence of nicotine non-abstinence vs. acute nicotine abstinence on cue-elicited activation of the ventral striatum. Eight female smokers underwent an event-related functional magnetic resonance imaging (fMRI) paradigm presenting randomized sequences of smoking-related and non-smoking related pictures. Participants were asked to indicate by a key press the gender of individuals in smoking-related and non-smoking related pictures (gender discrimination task), to maintain and evaluate attention to the pictures. There was a significant effect of smoking condition on reaction times (RT) for a gender discrimination task intended to assess and maintain attention to the photographs—suggesting a deprivation effect of acute nicotine abstinence and a statistical trend indicating greater RTs for smoking cues than neutral cues. BOLD contrast (smoking vs. non-smoking cues) was greater in the non-abstinent vs. acutely abstinent conditions in the ventral striatum including the nucleus accumbens (VS/NAc). Moreover, a significant positive correlation was observed between baseline cigarette craving prior to scanning and VS/NAc activation (r=0.84, p=0.009), but only in the non-abstinent condition. These results may either be explained by ceiling effects of nicotine withdrawal in the abstinent condition or, may indicate reduced relative activation (smoking vs. neutral contrast) in the VS/NAc in the abstinent vs. non-abstinent conditions in this group of female smokers.
fMRI; Smoking; Tobacco; Cue reactivity; Ventral striatum; Nucleus accumbens
Reactivity to smoking-related cues may be an important factor that precipitates relapse in smokers who are trying to quit. The neurobiology of smoking cue reactivity has been investigated in several fMRI studies. We combined the results of these studies using activation likelihood estimation, a meta-analytic technique for fMRI data. Results of the meta-analysis indicated that smoking cues reliably evoke larger fMRI responses than neutral cues in the extended visual system, precuneus, posterior cingulate gyrus, anterior cingulate gyrus, dorsal and medial prefrontal cortex, insula, and dorsal striatum. Subtraction meta-analyses revealed that parts of the extended visual system and dorsal prefrontal cortex are more reliably responsive to smoking cues in deprived smokers than in non-deprived smokers, and that short-duration cues presented in event-related designs produce larger responses in the extended visual system than long-duration cues presented in blocked designs. The areas that were found to be responsive to smoking cues agree with theories of the neurobiology of cue reactivity, with two exceptions. First, there was a reliable cue reactivity effect in the precuneus, which is not typically considered a brain region important to addiction. Second, we found no significant effect in the nucleus accumbens, an area that plays a critical role in addiction, but this effect may have been due to technical difficulties associated with measuring fMRI data in that region. The results of this meta-analysis suggest that the extended visual system should receive more attention in future studies of smoking cue reactivity.
smoking; cue reactivity; fMRI; meta-analysis; tobacco; addiction
In cigarette smokers, the most commonly-reported areas of brain activation during visual cigarette cue exposure are: the prefrontal, anterior cingulate, and visual cortices. We sought to determine changes in brain activity in response to cigarette cues when smokers actively resist craving.
Forty-two tobacco dependent smokers underwent functional magnetic resonance imaging, during which they were presented with videotaped cues. Three cue presentation conditions were tested: cigarette cues with subjects allowing themselves to crave (cigarette cue crave), cigarette cues with the instruction to resist craving (cigarette cue resist), and matched neutral cues.
Activation was found in the cigarette cue resist (compared to the cigarette cue crave) condition in the left dorsal anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and precuneus. Lower MR signal for the cigarette cue resist condition was found in the cuneus bilaterally, left lateral occipital gyrus, and right post-central gyrus. These relative activations and deactivations were more robust when the cigarette cue resist condition was compared to the neutral cue condition.
Suppressing craving during cigarette cue exposure involves activation of limbic (and related) brain regions and deactivation of primary sensory and motor cortices.
Nicotine Dependence; functional magnetic resonance imaging; cue-induced cigarette craving; cingulate cortex; visual cortex
Cigarette craving, one hallmark sign of nicotine dependence, is often measured in laboratory settings using cue reactivity methods. How lab measures of cue reactivity relate to real world smoking behavior is unclear, particularly among non-treatment seeking smokers. Within a larger study of hormonal effects on cue reactivity (N=78), we examined the predictive relationship of cue reactivity to smoking, each measured in several ways. Results indicated that cue-evoked craving in response to stressful imagery, and to a lesser extent, in vivo smoking cues, significantly predicted smoking behavior during the week following testing. However, this predictive relationship was absent upon controlling for reactivity to neutral cues. Nicotine dependence may moderate the relationship between cue reactivity and actual smoking, such that this predictive relationship is less robust among highly dependent smokers than among smokers low in nicotine dependence. The question of whether cue-elicited craving predicts smoking among smokers not in treatment is best answered with a qualified yes, depending on how craving is manipulated and measured. Our findings highlight important methodological and theoretical considerations for cue reactivity research.
cue reactivity; craving; dependence; smoking
A distributed network of brain regions is linked to drug-related cue responding. However, the relationships between smoking cue-induced phasic activity and possible underlying differences in brain structure, tonic neuronal activity and connectivity between these brain areas are as yet unclear. Twenty-two smokers and 22 controls viewed smoking-related and neutral pictures during a functional arterial spin labeling scanning session. T1, resting functional, and diffusion tensor imaging data were also collected. Six brain areas, dorsal lateral prefrontal cortex (dlPFC), dorsal medial prefrontal cortex (dmPFC), dorsal anterior cingulate cortex/cingulate cortex, rostral anterior cingulate cortex (rACC), occipital cortex, and insula/operculum, showed significant smoking cue-elicited activity in smokers when compared with controls and were subjected to secondary analysis for resting state functional connectivity (rsFC), structural, and tonic neuronal activity. rsFC strength between rACC and dlPFC was positively correlated with the cue-elicited activity in dlPFC. Similarly, rsFC strength between dlPFC and dmPFC was positively correlated with the cue-elicited activity in dmPFC while rsFC strength between dmPFC and insula/operculum was negatively correlated with the cue-elicited activity in both dmPFC and insula/operculum, suggesting these brain circuits may facilitate the response to the salient smoking cues. Further, the gray matter density in dlPFC was decreased in smokers and correlated with cue-elicited activity in the same brain area, suggesting a neurobiological mechanism for the impaired cognitive control associated with drug use. Taken together, these results begin to address the underlying neurobiology of smoking cue salience, and may speak to novel treatment strategies and targets for therapeutic interventions.
Smoking cue; anatomical; ASL; DTI; VBM; resting state functional connectivity
In untreated smokers, exposure to cigarette-related cues increases both the intensity of cigarette craving and relative glucose metabolism of the perigenual/ventral anterior cingulate cortex (ACC). Given that treatment with bupropion HCl reduces overall cigarette craving levels in nicotine dependent subjects, we performed a preliminary study of smokers to determine if bupropion HCl treatment attenuates cue-induced cigarette craving and associated brain metabolic activation. Thirty-seven, otherwise healthy smokers (20 untreated and 17 who had received open-label treatment with bupropion HCl) underwent two 18F-fluorodeoxyglucose positron emission tomography scanning sessions in randomized order—one when presented with neutral cues and the other when presented with cigarette-related cues. Bupropion-treated smokers had smaller cigarette cue-induced increases in craving scores on the Urge to Smoke (UTS) Scale and less activation of perigenual/ventral ACC metabolism from the neutral to the cigarette cue scan than untreated smokers. Thus, in addition to its known effects on spontaneous cigarette craving and withdrawal symptoms, bupropion HCl diminishes cue-induced cigarette craving and appears to attenuate cigarette cue-induced ACC activation. These results are consistent with the known effects of bupropion HCl, including its enhancement of catecholaminergic neurotransmission.
Positron emission tomography; Nicotine dependence; Brain metabolism; Anterior cingulate cortex; Orbitofrontal cortex; Bupropion hydrochloride
To examine whether gambling cue reactivity is cue-specific, 47 scratch-off lottery players and 47 horse race gamblers were presented with video clips of their preferred and non-preferred modes of gambling, and two control stimuli including an exciting car race and a mental stressor task while heart rates, excitement, and urge to gamble were being measured. Heart rates for both groups of gamblers were highest to the mental stressor and did not differ in response to the other three cues. Excitement for both groups was highest in response to the action cues (horse race and car chase). Urge to gamble was significantly higher for each group to their preferred mode of gambling. A post-hoc exploratory analysis comparing social gamblers (n=54) and probable pathological gamblers (n=40) revealed a similar pattern of responses. However, pathological gamblers reported overall significantly higher urges to gamble than social gamblers. As urges have been shown to play a pivotal role in addictive behaviors and relapse, the current findings may have implications for the development of gambling problems and relapse after successful treatment.
cue-reactivity; gambling; heart rate; excitement; urge
Gambling is a common recreational activity that becomes dysfunctional in a subset of individuals, with DSM ‘pathological gambling’ regarded as the most severe form. During gambling, players experience a range of cognitive distortions that promote an over-estimation of the chances of winning. Near-miss outcomes are thought to fuel these distortions. We observed previously that near-misses recruited overlapping circuitry to monetary wins in a study in healthy volunteers (Clark et al. 2009). The present study sought to extend these observations in regular gamblers and relate brain responses to an index of gambling severity. Twenty regular gamblers, who varied in their involvement from recreational players to probable pathological gamblers, were scanned whilst performing a simplified slot-machine task that delivered occasional monetary wins, as well as near-miss and full-miss non-win outcomes. In the overall group, near-miss outcomes were associated with a significant response in the ventral striatum, which was also recruited by monetary wins. Gambling severity, measured with the South Oaks Gambling Screen, predicted a greater response in the dopaminergic midbrain to near-miss outcomes. This effect survived controlling for clinical co-morbidities that were present in the regular gamblers. Gambling severity did not predict win-related responses in the midbrain or elsewhere. These results demonstrate that near-miss events during gambling recruit reward-related brain circuitry in regular players. An association with gambling severity in the midbrain suggests that near-miss outcomes may enhance dopamine transmission in disordered gambling, which extends neurobiological similarities between pathological gambling and drug addiction.
Gambling; Cognitive; Addiction; Dopamine; Striatum; Midbrain
There is evidence that women may be less successful when attempting to quit smoking than men. One potential contributory cause of this gender difference is differential craving and stress reactivity to smoking-and negative affect/stress-related cues. The present human laboratory study investigated the effects of gender on reactivity to smoking and negative affect/stress cues by exposing nicotine dependent women (n=37) and men (n=53) smokers to two active cue types, each with an associated control cue: 1) in vivo smoking cues and in vivo neutral control cues, and 2) imagery-based negative affect/stress script and a neutral/relaxing control script. Both before and after each cue/script, participants provided subjective reports of smoking-related craving and affective reactions. Heart rate (HR) and skin conductance (SC) responses were also measured. Results indicated that participants reported greater craving and SC in response to smoking vs. neutral cues and greater subjective stress in response to the negative affect/stress vs. neutral/relaxing script. With respect to gender differences, women evidenced greater craving, stress and arousal ratings and lower valence ratings (greater negative emotion) in response to the negative affect/stressful script. While there were no gender differences in responses to smoking cues, women trended towards higher arousal ratings. Implications of the findings for treatment and tobacco-related morbidity and mortality are discussed.
Aim: This functional magnetic resonance imaging (fMRI) study examined reactivity to alcohol, polydrug, marijuana and emotional picture cues in students who were referred to a college alcohol and drug assistance program. Methods: The fMRI data of 10 participants (5 females; 5 males) were collected while they viewed standardized emotional and appetitive cues. Results: Positive and negative emotional cues produced greater activity than neutral cues in the expected brain areas. Compared with neutral cues, alcohol cues produced greater brain activation in the right insula, left anterior cingulate, left caudate and left prefrontal cortex (Z = 2.01, 1.86, 1.82, 1.81, respectively; P < 0.05). Drug cues produced significantly greater left prefrontal activity compared with neutral cues, with polydrug cues activating the right insula and marijuana cues activating left anterior cingulate. Conclusions: Students at-risk for alcohol abuse showed neural reactivity to alcohol cues in four brain regions, which is consistent with their greater use of alcohol. Insula activation to appetitive cues may be an early marker of risk for progression to alcohol/drug abuse.
Pictorial representations of specific environments related to smoking can evoke robust craving to smoke, even in the absence of any proximal cues to smoke (e.g., cigarettes, lighters.) To evaluate the salience of smoking environment cues, we developed a novel procedure for bringing smokers’ real world smoking and nonsmoking environments into the laboratory to compare them with standard (i.e. not personalized) environments within a cue-reactivity paradigm. Seventy-two smokers used digital cameras to take pictures of the environments in which they do and do not smoke. They then completed a cue-reactivity session during which they viewed and rated pictures of smoking and nonsmoking environments, half personal and half standard, all devoid of proximal smoking cues. As hypothesized, personal environments led to a significantly larger smoking-nonsmoking difference in craving, compared with the standard environments. Personalization also enhanced stimuli vividness, relevance, positive affect, and excitement, as well as heart rate changes from baseline. Implications of these findings for exposure-based research and treatment for addiction, as well as other psychological disorders, are discussed.
tobacco; cue reactivity; context; conditioning
The internet represents a new and widely available forum for gambling. However, relatively few studies have examined internet gambling in adolescents. This study sought to investigate the correlates of at-risk or problem gambling amongst adolescents acknowledging or denying gambling on the internet.
Survey data from 2,006 Connecticut high-school-student gamblers were analyzed using chi-square and logistic regression analyses.
At-risk/problem gambling was found more frequently in adolescent internet gamblers than in non-internet gamblers. As compared to at-risk/problem gambling in the non-internet gambling group, at-risk/problem gambling in the internet gambling group was more strongly associated with poor academic performance and substance use (particularly current heavy alcohol use; odds ratio=2.99; p=0.03) and less strongly associated with gambling with friends (odds ratio=0.32; p=0.0003). At-risk/problem gambling in both the internet and non-internet gambling groups, respectively, was associated at p<0.05 each with multiple adverse measures including dysphoria/depression (odds ratios=1.76, 1.96), getting into serious fights (odds ratios=2.50, 1.93), carrying weapons (odds ratios=2.11, 1.90), and use of tobacco (odds ratios=2.05, 1.88 for regular use), marijuana (odds ratios=2.02, 1.39) and other drugs (odds ratios=3.24, 1.67).
Clinically, it is important to assess for teenagers’ involvement in internet gambling, particularly as adolescent at-risk/problem internet gambling appears specifically associated with non-peer involvement, heavy alcohol use and poor academic functioning.
gambling; adolescence; internet; risk behaviors; substance use
In recent years, research applying functional neuroimaging to the study of cue-elicited drug craving has emerged. This research has begun to identify a distributed system of brain activity during drug craving. A review of this literature suggested that expectations regarding the opportunity to use a drug affected the pattern of neural responses elicited by drug cues. Using functional magnetic resonance imaging (fMRI), we examined the effects of smoking expectancy on the neural response to neutral (e.g., roll of tape) and smoking-related (a cigarette) stimuli in male cigarette smokers deprived of nicotine for 8 hr. As predicted, several brain regions (e.g., the anterior cingulate cortex) exhibited differential activation during cigarette versus neutral cue exposure. Moreover, we found that subregions of the prefrontal cortex (i.e., ventromedial, ventrolateral, and dorsolateral prefrontal cortices) showed cue-elicited activation that was modulated by smoking expectancy. These results highlight the importance of perceived drug use opportunity in the neurobiological response to drug cues.
Impulsivity has been shown to play a pivotal role in the onset, pattern of consumption, relapse and, most notably, craving of illicit and licit drugs such as cigarette smoking. The goal of this study was to examine the neurobiological influence of trait impulsivity during cue-induced cigarette craving. Thirty-one chronic smokers passively viewed appetitive smoking-related and neutral images while being scanned and reported their feelings of craving. They completed the Barratt Impulsiveness Scale, a measure of trait impulsivity. We conducted functional connectivity analyses using the psycho-physiological interaction method. During the processing of smoking stimuli, participants presented increased activations in the cingulate and prefrontal cortices. We observed a significant positive relationship between impulsivity scores and reported craving. A negative correlation was observed between the impulsivity score and activity in the posterior cingulate cortex (PCC). The insula, dorsal anterior cingulate cortex (dACC) as well as the dorsolateral prefrontal cortex (DLPFC) presented a negative connectivity with the PCC. Consistent with the view that the PCC is related to the ability to resist cigarette craving, our results suggest that high impulsive smokers have greater difficulty in controlling their cravings, and that this weakness may be mediated by lower PCC activity. Moreover, we argue that the less PCC activity, the greater the probability of a stronger emotional, physiological, and biased attentional response to smoking cues mediated by insula, dACC, and DLPFC activity. This is the first study on this topic, and so, results will need to be replicated in both licit and illicit drug abusers. Our findings also highlight a need for more emphasis on the PCC in drug addiction research, as it is one of the most consistently activated regions in functional magnetic resonance imaging studies examining the neural correlates of cue-induced alcohol, drug, and tobacco cravings.
craving; impulsivity; cigarette smoking; neural correlates; fMRI
The purpose of this study was to compare the socio-demographic characteristics of non-problem gamblers, problem gamblers and pathological gamblers, to investigate the association between gambling related factors and perceived health and well-being among the three subgroups of gamblers, and to analyse simultaneously socio-demographic characteristics, gambling related factors and perceived health and well-being and the severity of disordered gambling (problem gamblers and pathological gamblers).
The data were collected through a nationwide telephone survey in 2011. Participants were selected through a random population sample of 15-74-year-old Finns. From that sample, persons with any past-year gambling involvement (N = 3451) were selected for a subsample for the descriptive and inferential analysis in the present paper. Gambling was assessed using the South Oaks Gambling Screen. Statistical significance was determined by chi-squared tests. The odds ratio and effect size were computed by using multivariate-adjusted multinomial logistic regression analysis.
The most significant socio-demographic characteristics (male gender, young age, education ≤12 years), gambling related factors (slot machine gambling, internet gambling) and perceived health and well-being (feeling lonely, smoking daily, risky alcohol consumption, mental health problems) explained 22.9 per cent of the variation in the severity of disordered gambling.
Male gender and loneliness were found to be associated with problem gambling in particular, along with smoking and risky alcohol consumption. Mental health problems and risky alcohol consumption were associated with pathological gambling. These identified associations between disordered gambling, mental health problems and risky alcohol consumption should be taken into consideration when implementing screenings of disordered gambling.
Disordered gambling; Pathological gambling; Population survey; Problem gambling; Public health; South Oaks Gambling Screen
Cue reactivity paradigms are well-established laboratory procedures used to examine subjective craving in response to substance-related cues. For smokers, the relationship between nicotine dependence and cue reactivity has not been clearly established. The main aim of the present study was to further examine this relationship.
Participants (N=90) were between the ages 18–40 and smoked ≥10 cigarettes per day. Average nicotine dependence (Fagerström Test for Nicotine Dependence; FTND) at baseline was 4.9 (SD=2.1). Participants completed four cue reactivity sessions consisting of two in vivo cues (smoking, neutral) and two affective imagery cues (stressful, relaxed), all counterbalanced. Craving in response to cues was assessed following each cue exposure using the Questionnaire of Smoking Urges—Brief (QSU-B). Differential cue reactivity was operationally defined as the difference in QSU scores between the smoking and neutral cues, and between the stressful and relaxed cues.
Nicotine dependence was significantly and negatively associated with differential cue reactivity scores in regards to hedonic craving (QSU factor 1) for both in vivo and imagery cues, such that those who had low FTND scores demonstrated greater differential cue reactivity than those with higher FTND scores (β = −.082; p = .037; β = −.101; p = .023, respectively). Similar trends were found for the total QSU and for negative reinforcement craving (QSU factor 2), but did not reach statistical significance.
Under partially sated conditions, less dependent smokers may be more differentially cue reactive to smoking cues as compared to heavily dependent smokers. These findings offer methodological and interpretative implications for cue reactivity studies.
cue reactivity; craving; dependence; smoking; nicotine
The cue reactivity paradigm has been used extensively in laboratory settings to study cue-specific craving responses to drug-related cues. However, this procedure has been used in only one study to assess craving in the drug user’s natural environment (Warthen & Tiffany, 2009). The present study combined cue-reactivity with ecological momentary assessment (CREMA) to evaluate smokers’ cue reactions in natural environments as a further validation and extension of this procedure. A total of 66 daily cigarette smokers carried a personal digital assistant (PDA) and had the opportunity to respond to 32 cue reactivity sessions across eight days. Cues were presented through in vivo and photographic modes. During in vivo sessions, participants handled and looked at a cigarette or neutral object, while during photographic sessions, participants looked at a smoking related or neutral photograph on the PDA. Craving and mood were assessed before and after cue presentations. Cues were also presented in the laboratory both before (Lab I) and after (Lab II) the eight-day CREMA procedure. Participants completed over 90% of cue-reactivity sessions delivered with the CREMA procedure. Analyses revealed robust cue-reactivity in the natural environment and laboratory across both modes of presentation. Photographic cues elicited significantly stronger cue-reactivity effects than in vivo cues across all sessions. The CREMA procedure has been shown to elicit robust cue-reactivity effects across multiple modes of cue presentation. Results support the use of the CREMA procedure for examining cue-specific craving in the natural environment of smokers.
Craving; Cue-Reactivity; Ecological Momentary Assessment; Tobacco; Cigarettes
Attenuation of cue-elicited craving with brain stimulation techniques is a growing area of attention in addiction research. This investigation aims to guide these studies by assessing individual variability in the location of peak cortical activity during cue-elicited craving.
Twenty-six nicotine-dependent individuals performed a cue-elicited craving task in a 3T MRI scanner while BOLD signal data was collected. The task included epochs of smoking cues, neutral cues, and rest. The location of peak activity during smoking cues relative to neutral cues (‘hot spot’) was isolated for each individual. The spatial dispersion of the 26 cue-elicited hot spots (1 per participant) was quantified via hierarchical clustering.
When viewing nicotine cues all 26 participants had at least one cluster of significant prefrontal cortex activity (p<0.05, cluster corrected). Only 62% had peak activity in the medial prefrontal cortex cluster (including 100% of the men). In 15% of the participants peak activity was located in either the left lateral prefrontal cortex or left insula cluster. Peak activity in the remaining 23% was dispersed throughout the prefrontal cortex.
There is considerable individual variability in the location of the cue-elicited ‘hot spot’ as measured by BOLD activity. Men appear to have a more uniform location of peak BOLD response to cues than women. Consequently, acquiring individual functional imaging data may be advantageous for either tailoring treatment to the individual or filtering participants before enrollment in treatment.
nicotine; craving; functional MRI; transcranial magnetic stimulation
The behavioral approach system (BAS) from Gray’s reinforcement sensitivity theory is a neurobehavioral system involved in the processing of rewarding stimuli that has been related to dopaminergic brain areas. Gray’s theory hypothesizes that the functioning of reward brain areas is modulated by BAS-related traits. To test this hypothesis, we performed an fMRI study where participants viewed erotic and neutral pictures, and cues that predicted their appearance. Forty-five heterosexual men completed the Sensitivity to Reward scale (from the Sensitivity to Punishment and Sensitivity to Reward Questionnaire) to measure BAS-related traits. Results showed that Sensitivity to Reward scores correlated positively with brain activity during reactivity to erotic pictures in the left orbitofrontal cortex, left insula, and right ventral striatum. These results demonstrated a relationship between the BAS and reward sensitivity during the processing of erotic stimuli, filling the gap of previous reports that identified the dopaminergic system as a neural substrate for the BAS during the processing of other rewarding stimuli such as money and food.
Drug-associated stimuli (cues) have a prominent role in addiction research because they are able to provoke craving and relapses. Generally, drug cues are seen as conditioned excitatory stimuli, which elicit drug seeking and usage. However, newer data suggest differential effects for smoking stimuli depending on their stage in the smoking ritual. Specifically, stimuli associated with the terminal stage of smoke consumption (END-stimuli) may evoke reactivity opposite to the reactivity evoked by stimuli associated with the beginning of smoke consumption (BEGIN-stimuli). This fMRI study compared 20 nondeprived smokers with 20 nonsmokers to unravel the influence of smoking-related pictures displaying the beginning (BEGIN-stimuli) and termination (END-stimuli) of the smoking ritual on neural activity in the addiction network. In addition, 20 deprived smokers (12 h deprivation) were investigated to explore the effects of deprivation on the processing of these stimuli. In nondeprived smokers, BEGIN-stimuli reliably activated the addiction network (for example, the ventral striatum, orbitofrontal cortex, and anterior cingulate cortex (ACC)). In contrast, END-stimuli triggered a differential pattern of activations as well as deactivations; deactivations were found in the ventral striatum and the ACC. Deprivation had no clear effect on the responses triggered by BEGIN-stimuli, but affected the reactivity to END-stimuli. Our data clearly suggest that stimuli associated with different stages of the smoking ritual trigger differential neuronal responses. While BEGIN-stimuli generally seem to activate the addiction network, END-stimuli presumably have some inhibitory properties. This new finding might add to a more differentiated understanding of cue reactivity and addiction.
addiction; smoking; cue reactivity; fMRI; deprivation; terminal stimuli; Addiction & Substance Abuse; Biological Psychiatry; Learning & Memory; Imaging; Clinical or Preclinical; addiction; smoking; cue-reactivity; fMRI; deprivation; terminal stimuli
Attentional bias for drug-related stimuli, as measured by emotional Stroop (ES) tasks, is predictive of treatment outcomes for tobacco smoking and other abused drugs. Characterizing relationships between smoking-related attentional bias and brain reactivity to smoking images may help identify neural substrates critical to relapse vulnerability. To this end, we investigated putative relations between interference effects in an offline smoking ES task and functional MRI (fMRI) measures of brain reactivity to smoking versus neutral images in women smokers. Positive correlations were found between attentional bias and reactivity to smoking images in brain areas involved in emotion, memory, interoception, and visual processing including the amygdala, hippocampus, parahippocampal gyrus, insula, and occipital cortex. These findings suggest that smokers with elevated attentional biases to smoking-related stimuli may more readily shift attention away from other external stimuli and toward smoking stimuli-induced internal states and emotional memories. Such attentional shifts may contribute to increased interference by smoking cues, possibly increasing relapse vulnerability. Treatments capable of inhibiting shifts to drug cue-induced memories and internal states may lead to personalized tobacco dependence treatment for smokers with high attentional bias to smoking-related stimuli.
fMRI; smoking; Smoking Emotional Stroop; interference; interoception; memory