Cue Exposure Task Research Articles

Alcohol cue reactivity in the brain: Age-related differences in the role of social processes in addiction in male drinkers.

Social attunement (SA)-the tendency to harmonize behavior with the social environment-has been proposed to drive the escalation of alcohol use in adolescence, while reducing use in adulthood. Little is known about how heightened social sensitivity in adolescence may interact with neural alcohol cue reactivity-a marker of alcohol use disorder-and its relationship to alcohol use severity over time. The aims of this study were to test whether (1) adolescents and adults differ in social alcohol cue reactivity in the nucleus accumbens, anterior cingulate cortex, and right medial prefrontal cortex (mPFC), and (2) age moderates the relationship between social alcohol cue reactivity and social attunement, measures of drinking at baseline, and changes in drinking over time. A sample of male adolescents (16-18 years) and adults (29-35 years) completed an fMRI social alcohol cue-exposure task at baseline and an online follow-up two to three years later. No main effects of age or drinking measures were observed in social alcohol cue reactivity. However, age significantly moderated associations of social alcohol cue reactivity in the mPFC and additional regions from exploratory whole-brain analyses with SA, with a positive association in adolescents and negative association in adults. Significant age interactions emerged only for SA in predicting drinking over time. Adolescents with higher SA scores escalated drinking, while adults with higher SA scores reduced drinking. These findings warrant further research on SA as a risk and protective factor and suggest that social processes influence cue reactivity differentially in male adolescents and adults.

Stimulation of the dorsolateral prefrontal cortex modulates brain cue reactivity to reward (un)availability

Brain imaging studies have shown that stimulation of the left dorsolateral prefrontal cortex (dlPFC), which plays a pivotal role in high-order cognitive control processes, modulates brain reactivity to reward-related cues. Nevertheless, the impact of contextual factors such as reward availability (the reward that is depicted in the cue exposure task) on such modulation effect remains unclear. Here we tested whether a single session of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) over the left dlPFC differently impacts brain reactivity to cues signalling either availability or unavailability of a sports betting opportunity. Employing a within-subject design (verum versus sham HF-rTMS) among thirty-two frequent sports bettors, we first observed that, as compared to the sham condition, verum HF-rTMS modulated brain reactivity to game cues prior to being made (un)available for betting, through simultaneous increases (posterior insula and caudate nucleus) and decreases (occipital pole) in brain activation. Second, verum HF-rTMS led to increased ventral striatal activity towards cues available for betting but did not modulate brain response to cues unavailable for betting. Taken together, these findings demonstrate that transient stimulation of the left dlPFC led to a general modulation in brain activity in responses to cues, and that this effect is only partly dependent on cues signalling for reward (un)availability.

The Moderating Role of Sex in the Relation between Cue-Induced Craving and Resting-State Functional Connectivity in the Salience Network of Non-Clinically Diagnosed Drinkers

Introduction: Previous research indicates a relation between craving and increased connectivity in the resting-state salience network. However, the link between cue-induced craving and connectivity in the salience network remains unclear. Further investigation is needed to understand the effect of sex on the relationship between cue-induced craving and the salience network. We investigated the role of sex in the association between the resting-state functional connectivity (RSFC) salience network and subjective cue-induced craving. Methods: Twenty-six males (mean age = 25.3) and 23 females (mean age = 26.0), with a score of 12 or higher on the alcohol use disorder identification test, were included in the current study. No significant difference in age was observed between males and females. Participants underwent a resting-state MRI scan for 6 min. Following the MRI scan, participants completed an alcohol cue-exposure task for 5.5 min to assess cue-induced craving using the desire to drink alcohol questionnaire. We applied independent component analysis methods to determine functional connectivity within the salience network. Subsequently, we investigated how cue-induced craving is related to the salience network’s RSFC and if this relationship is moderated by sex. Results: The association between the salience network and cue-induced craving was not statistically significant nor did we find a moderating effect for sex. Conclusion: The null findings in the study may be explained by a lack of power. Alternatively, alcohol use sex disparities may be more prevalent in the recreational/impulsive stage, whereas participants in our study were in the later stage of addiction.

Multimodal Assessment of Smoking cue Reactivity During a Smoking Cue Exposure Task.

Background. Cue-reactivity as a characteristic symptom of substance use disorders (SUD) is highly context dependent. Paradigms with high context validity need to be established for the investigation of underlying neurobiological mechanisms. While craving can be assessed by self-report as one aspect of cue-reactivity (CR), the assessment of biological measures such as the autonomous response and EEG promises a holistic perspective including CR at an automatized level. In a multimodal approach, smoking cue exposure (CE) effects on heart rate variability (HRV), EEG frequency power, and craving as well as their interrelation were assessed. This pilot study focused on the validity of CR measurements in a naturalistic CE paradigm. Methods. EEG frequency power, HRV, and craving were assessed during resting state (RS) and smoking CE in smokers (n = 14) and nonsmoking controls (n = 10) to investigate the psychophysiological and subjective reactions to CE. Results. Increased beta power was found only in smokers during CE compared to the control condition. There was an inverse correlation of beta power and maximum craving. Likewise, HRV correlated negatively with maximum smoking urges in smokers immediately after the measurements, without differentiation between CE and control condition. Conclusion. The increased beta power in smokers during CE is discussed as increased inhibitory control related to reduced craving in smokers. Furthermore, increased craving during CE seems to be associated to decreased vagal activity. The multimodal measurements during the CE showed ecological validity to be fundamental for CE assessment in clinical populations to evaluate its predictive value.

Using Virtual Reality to Induce and Assess Objective Correlates of Nicotine Craving: Paradigm Development Study.

BackgroundCraving is a clinically important phenotype for the development and maintenance of nicotine addiction. Virtual reality (VR) paradigms are successful in eliciting cue-induced subjective craving and may even elicit stronger craving than traditional picture-cue methods. However, few studies have leveraged the advances of this technology to improve the assessment of craving.ObjectiveThis report details the development of a novel, translatable VR paradigm designed to both elicit nicotine craving and assess multiple eye-related characteristics as potential objective correlates of craving.MethodsA VR paradigm was developed, which includes three Active scenes with nicotine and tobacco product (NTP) cues present, and three Neutral scenes devoid of NTP cues. A pilot sample (N=31) of NTP users underwent the paradigm and completed subjective measures of nicotine craving, sense of presence in the VR paradigm, and VR-related sickness. Eye-gaze fixation time (“attentional bias”) and pupil diameter toward Active versus Neutral cues, as well as spontaneous blink rate during the Active and Neutral scenes, were recorded.ResultsThe NTP Cue VR paradigm was found to elicit a moderate sense of presence (mean Igroup Presence Questionnaire score 60.05, SD 9.66) and low VR-related sickness (mean Virtual Reality Sickness Questionnaire score 16.25, SD 13.94). Scene-specific effects on attentional bias and pupil diameter were observed, with two of the three Active scenes eliciting greater NTP versus control cue attentional bias and pupil diameter (Cohen d=0.30-0.92). The spontaneous blink rate metrics did not differ across Active and Neutral scenes.ConclusionsThis report outlines the development of the NTP Cue VR paradigm. Our results support the potential of this paradigm as an effective laboratory-based cue-exposure task and provide early evidence of the utility of attentional bias and pupillometry, as measured during VR, as useful markers for nicotine addiction.

Effects of electronic cigarette e-liquid flavouring on cigarette craving

BackgroundE-liquid flavour restrictions may discourage electronic cigarette (e-cigarette) uptake among youth. However, possible unintended consequences may include reduced appeal and effectiveness of e-cigarettes for smoking cessation. Non-tobacco flavours appear to...

Pain and reward circuits antagonistically modulate alcohol expectancy to regulate drinking

Expectancy of physical and social pleasure (PSP) promotes excessive drinking despite the potential aversive effects of misuse, suggesting an imbalance in the response to reward and pain in alcohol seeking. Here, we investigated the competing roles of the reward and pain circuits in PSP expectancy and problem drinking in humans. Using fMRI data during resting (n = 180) and during alcohol cue exposure (n = 71), we examined the antagonistic effects of the reward-related medial orbitofrontal cortex (mOFC) and pain-related periaqueductal gray (PAG) connectivities on PSP expectancy and drinking severity. The two regions’ connectivity maps and strengths were characterized to assess their shared substrates and net relationship with PSP expectancy. We evaluated mediation and path models to further delineate how mOFC and PAG connectivities interacted through the shared substrates to differentially impact expectancy and alcohol use. During resting, whole-brain regressions showed mOFC connectivity in positive and PAG connectivity in negative association with PSP scores, with convergence in the precentral gyrus (PrCG). Notably, greater PAG-PrCG relative to mOFC-PrCG connectivity strength predicted lower PSP expectancy. During the alcohol cue exposure task, the net strength of the PAG vs. mOFC cue-elicited connectivity with the occipital cortex again negatively predicted PSP expectancy. Finally, mediation and path models revealed that the PAG and mOFC connectivities indirectly and antagonistically modulated problem drinking via their opposing influences on expectancy and craving. Thus, the pain and reward circuits exhibit functional antagonism such that the mOFC connectivity increases expectancy of drinking pleasure whereas the PAG serves to counter that effect.

Dynamic functional connectivity between nucleus accumbens and the central executive network relates to chronic cannabis use.

The neural mechanisms of drug cue‐reactivity regarding the temporal fluctuations of functional connectivity, namely the dynamic connectivity, are sparsely studied. Quantifying the task‐modulated variability in dynamic functional connectivity at cue exposure can aid the understanding. We analyzed changes in dynamic connectivity in 54 adult cannabis users and 90 controls during a cannabis cue exposure task. The variability was measured as standard deviation in the (a) connectivity weights of the default mode, the central executive, and the salience networks and two reward loci (amygdalae and nuclei accumbens); and (b) topological indexes of the whole brain (global efficiency, modularity and network resilience). These were compared for the main effects of task conditions and the group (users vs. controls), and correlated with pre‐ and during‐scan subjective craving. The variability of connectivity weights between the central executive network and nuclei accumbens was increased in users throughout the cue exposure task, and, was positively correlated with during‐scan craving for cannabis. The variability of modularity was not different by groups, but positively correlated with prescan craving. The variability of dynamic connectivity during cannabis cue exposure task between the central executive network and the nuclei accumbens, and, the level of modularity, seem to relate to the neural underpinning of cannabis use and the subjective craving.

A Preliminary Examination of Nicotine-Free Electronic Cigarette Use During Cessation From Combustible Cigarettes.

Despite the availability of smoking cessation strategies, smoking cue-induced craving remains a relatively untreated relapse risk factor. Utilizing nicotine-free electronic cigarettes (e-cigarettes) to extinguish the motivational influence of smoking cues may be a viable approach to address cue reactivity. In this pilot study, 26 daily tobacco smokers used nicotine-free e-cigarettes while being maintained on daily transdermal sustained-release nicotine replacement therapy (NRT) to mitigate pharmacological withdrawal. Sensitivity to cue-induced craving, measured by the rise in craving after a visual cue exposure task, was assessed at a baseline visit after smoking as usual and again after 2 weeks of nicotine-free e-cigarette and NRT use. Participants’ pattern and amount of tobacco cigarette smoking were evaluated on both visits and 1 month posttreatment. Cue-induced craving significantly decreased after the 2-week intervention, yet withdrawal scores increased during this time. One month after study completion, participants continued to report significantly lower overall cigarette craving and conventional tobacco cigarette use. Including the 34.8% that were totally abstinent, 65.2% reported smoking fewer than 10 cigarettes per week (compared to 87.2 per week at baseline for the entire group). A linear regression revealed that greater baseline cue-induced craving predicted better outcomes, whereas more withdrawal at the e-cigarette visit was related to more smoking at 1 month. This proof-of-concept pilot study suggests that the addition of ad libitum nicotine-free e-cigarettes to an existing strategy of transdermal NRT may attenuate cue-induced craving for tobacco smoking. A larger sample that is powered for detecting additional factors and longer-term outcomes is warranted.

Facing temptation: The neural correlates of gambling availability during sports picture exposure.

Nowadays, sports betting has become increasingly available and easy to engage in. Here we examined the neural responses to stimuli that represent sporting events available for betting as compared to sporting events without a gambling opportunity. We used a cue exposure task in which football (soccer) fans (N = 42) viewed cues depicting scheduled football games that would occur shortly after the scanning session. In the "betting" condition, participants were instructed to choose, at the end of each block, the game (and the team) they wanted to bet on. In the "watching" condition, participants chose the game they would prefer to watch. After the scanning session, participants completed posttask rating questionnaires assessing, for each cue, their level of confidence about the team they believed would win and how much they would enjoy watching the game. We found that stimuli representing sport events available for betting elicited higher fronto-striatal activation, as well as higher insular cortex activity and functional connectivity, than sport events without a gambling opportunity. Moreover, games rated with more confidence towards the winning team resulted in greater brain activations within regions involved in affective decision-making (ventromedial prefrontal cortex), cognitive inhibitory control (medial and superior frontal gyri) and reward processing (ventral and dorsal striatum). Altogether, these novel findings offer a sensible simulation of how the high availability of sports betting in today's environment impacts on the reward and cognitive control systems. Future studies are needed to extend the present findings to a sample of football fans that includes a samilar proportion of female and male participants.

The left dorsolateral prefrontal cortex and caudate pathway: New evidence for cue-induced craving of smokers.

Although the activation of the prefrontal cortex (PFC) and the striatum had been found in smoking cue induced craving task, whether and how the functional interactions and white matter integrity between these brain regions contribute to craving processing during smoking cue exposure remains unknown. Twenty-five young male smokers and 26 age- and gender-matched nonsmokers participated in the smoking cue-reactivity task. Craving related brain activation was extracted and psychophysiological interactions (PPI) analysis was used to specify the PFC-efferent pathways contributed to smoking cue-induced craving. Diffusion tensor imaging (DTI) and probabilistic tractography was used to explore whether the fiber connectivity strength facilitated functional coupling of the circuit with the smoking cue-induced craving. The PPI analysis revealed the negative functional coupling of the left dorsolateral prefrontal cortex (DLPFC) and the caudate during smoking cue induced craving task, which positively correlated with the craving score. Neither significant activation nor functional connectivity in smoking cue exposure task was detected in nonsmokers. DTI analyses revealed that fiber tract integrity negatively correlated with functional coupling in the DLPFC-caudate pathway and activation of the caudate induced by smoking cue in smokers. Moreover, the relationship between the fiber connectivity integrity of the left DLPFC-caudate and smoking cue induced caudate activation can be fully mediated by functional coupling strength of this circuit in smokers. The present study highlighted the left DLPFC-caudate pathway in smoking cue-induced craving in smokers, which may reflect top-down prefrontal modulation of striatal reward processing in smoking cue induced craving processing. Hum Brain Mapp 38:4644-4656, 2017. © 2017 Wiley Periodicals, Inc.

Attentional bias to alcohol stimuli predicts elevated cue-induced craving in young adult social drinkers

Considerable evidence has identified biased cognitive processing of alcohol-related stimuli as an important factor in the maintenance of alcohol-seeking and relapse among individuals suffering from alcohol use-disorders (AUDs). In addition, a large body of research has demonstrated that exposure to alcohol cues can elicit powerful alcohol cravings. Little is known, however, about the possible relationship between attentional bias and cue-induced cravings, and even less is known about these processes in social drinkers without a personal history of AUDs. The goal of this study was to examine the possibility that attentional biases toward alcohol-related stimuli would predict elevated cue-induced alcohol craving in this population. Young adult social drinkers (N=30, Mean age=22.8±1.9, 61% female) recruited from an urban university population completed a visual dot probe task in which they were presented with alcohol and neutral stimulus pictures that were immediately followed by a visual probe replacing one of the pictures. Attentional bias was measured by calculating reaction times to probes that replaced alcohol stimuli vs. neutral stimuli. Participants then completed a classic alcohol cue-exposure task and reported cravings immediately before and after alcohol and neutral cue-exposures. Not surprisingly, exposure to alcohol cues elicited significant cravings. Consistent with the study hypothesis, larger attentional biases toward alcohol stimuli predicted higher levels of alcohol craving. Findings demonstrate that heightened attention to alcohol stimuli can significantly impact motivation to consume in healthy young adults, and suggest a possible pathway linking cognitive processes early in the drinking trajectory to the later development of AUDs.

Quit interest influences smoking cue-reactivity

Interest in quitting smoking is important to model in cue-reactivity studies, because the craving elicited by cue exposure likely requires different self-regulation efforts for smokers who are interested in quitting compared to those without any quit interest. The objective of the current study was to evaluate the role of quit interest in how cigarette cue exposure influences self-control efforts. Smokers interested in quitting (n=37) and smokers with no interest in quitting (n=53) were randomly assigned to a cigarette or neutral cue exposure task. Following the cue exposure, all participants completed two self-control tasks, a measure of risky gambling (the Iowa Gambling Task) and a cold pressor tolerance task. Results indicated that smokers interested in quitting had worse performance on the gambling task when exposed to a cigarette cue compared to neutral cue exposure. We also found that people interested in quitting tolerated the cold pressor task for a shorter amount of time than people not interested in quitting. Finally, we found that for people interested in quitting, exposure to a cigarette cue was associated with increased motivation to take steps toward decreasing use. Overall these results suggest that including quit interest in studies of cue reactivity is valuable, as quit interest influenced smoking cue-reactivity responses.

Overweight adolescents' brain response to sweetened beverages mirrors addiction pathways.

Many adolescents struggle with overweight/obesity, which exponentially increases in the transition to adulthood. Overweight/obesity places youth at risk for serious health conditions, including type 2 diabetes. In adults, neural substrates implicated in addiction (e.g., orbitofrontal cortex (OFC), striatum, amygdala, and ventral tegmental area) have been found to be relevant to risk for overweight/obesity. In this study, we examined three hypotheses to disentangle the potential overlap between addiction and overweight/obesity processing by examining (1) brain response to high vs. low calorie beverages, (2) the strength of correspondence between biometrics, including body mass index (BMI) and insulin resistance, and brain response and (3) the relationship between a measure of food addiction and brain response using an established fMRI gustatory cue exposure task with a sample of overweight/obese youth (M age=16.46; M BMI=33.1). Greater BOLD response was observed across the OFC, inferior frontal gyrus (IFG), nucleus accumbens, right amygdala, and additional frontoparietal and temporal regions in neural processing of high vs. low calorie beverages. Further, BMI scores positively correlated with BOLD activation in the high calorie > low calorie contrast in the right postcentral gyrus and central operculum. Insulin resistance positively correlated with BOLD activation across the bilateral middle/superior temporal gyrus, left OFC, and superior parietal lobe. No relationships were observed between measures of food addiction and brain response. These findings support the activation of parallel addiction-related neural pathways in adolescents'high calorie processing, while also suggesting the importance of refining conceptual and neurocognitive models to fit this developmental period.

Cue reactivity in smokers: An event-related potential study

Drugs-of-abuse may increase the salience of drug cues by sensitizing the dopaminergic (DA) system (Robinson and Berridge, 1993), leading to differential attention to smoking stimuli. Event-related potentials (ERPs) have been used to assess attention to smoking cues but not using an ERP component associated with DA-mediated salience evaluation. In this study the DA-related P2a and the P3, were compared in smokers (N=21) and non-smokers (N=21) during an attention selection cue exposure task including both cigarette and neutral images. We predicted that both the P2a and P3 would be larger to targets than non-targets, but larger to non-target cigarette images than non-target neutral images only in the smokers, reflecting smokers' evaluation of smoking stimuli as relevant even when they were not targets. Results indicated that smokers showed behavioral cue reactivity, with more false alarms to cigarette images (responding to cigarette images when they were not targets) than non-smokers; however, both smokers and non-smokers had a larger P2a and P3 to cigarette images. Thus, while smokers showed behavioral evidence of differential salience evaluation of the cigarette images, this group difference was not reflected in differential brain activity. These findings may reflect characteristics of the ERPs (both ERP components were smaller in the smokers), the smoking sample (they were not more impulsive, i.e. reward sensitive, than the non-smokers, in contrast to prior studies) and the design (all participants were aware that the aim of the study was related to smoking).

Cue-Induced Smoking Urges Deplete Cigarette Smokers’ Self-Control Resources

Exposure to smoking-related cues leads to increased urge to smoke in regular cigarette smokers and resisting these urges requires considerable self-control. Adopting a resource depletion model, two studies tested the hypothesis that resisting smoking urges depletes self-control resources. Adopting a within-participants randomized cross-over design, participants (study 1, N = 19; study 2, N = 32) were exposed to smoking-related (study 1: smoking images; study 2: cigarette cue-exposure task) and neutral (study 1: neutral images; study 2: drinking-straw task) cues with presentation order randomized. After each cue set, participants completed self-control tasks (study 1: handgrip task; study 2: handgrip and Stroop tasks), performance on which constituted dependent measures of self-control. Self-control task performance was significantly impaired when exposed to smoking-related cues compared to neutral cues. No significant presentation-order effects, or interaction effects between stimulus and presentation order, were found. Findings corroborate our hypothesis that resisting smoking urges depletes cigarette smokers' self-control resources and suggests that self-control capacity is governed by a limited resource.

The Effect of d-Cycloserine on Subliminal Cue Exposure in Spider Fearful Individuals

Research on d-cycloserine (DCS) has demonstrated a significant effect on symptom reduction in human studies that utilized conventional exposure-based approaches. Recent studies have offered promising results for targeting fears through subliminal paradigms. In this double-blind, randomized placebo-controlled study, 45 spider fearful individuals received DCS or placebo pills prior to completing a subliminal cue exposure task to images of spiders. Participants completed self-report questionnaires and a behavioral approach task to a live caged tarantula. After repeated exposure to subliminal spider cues, participants in the DCS group reported a greater reduction in disgust than individuals in the placebo group. No difference was observed in fear ratings. These findings suggest that DCS augments the reduction in disgust in spider fearful subjects after subliminal exposure to spider cues.

Evaluation of the Alcohol Craving Questionnaire-Now factor structures: Application of a cue reactivity paradigm

The current study compared the psychometric properties and clinical/research utility of four distinct factor/subscale models of alcohol craving (three factor-derived models, and one rationally derived model) as measured by the Alcohol Craving Questionnaire-Now in social ( n = 52) and alcohol dependent ( n = 71) drinkers. All participants completed a self-report measure of alcohol abuse in addition to engaging in a structured interview and cue reactivity protocol. Participants provided self-reported craving, as well as desire to approach or avoid drinking, during a cue exposure task using separate analog scales. Factor/subscale models were compared in terms of internal consistency, convergent and divergent validity, and ability to predict cue-elicited approach and craving in addition to diagnostic status. All models demonstrated high levels of internal consistency, convergent and divergent validity, and the ability to predict both cue-elicited craving and alcohol dependence status. Specific strengths and weaknesses of each model are examined and the theoretical, clinical, and research utility of the current findings are discussed.

Alcohol-related motivational tendencies in hazardous drinkers: assessing implicit response tendencies using the modified-IAT

This study examined the utility of an implicit measure of cognitive associations, the Implicit Association Test (IAT; Greenwald, McGhee, & Schwartz, 1998), to assess alcohol-related approach dispositions. Forty-seven hazardous drinkers completed a modified IAT procedure that assessed the relation between alcohol and behavioral categories (i.e., approach and avoid). Participants completed a series of individual difference measures before an alcohol cue exposure task in which they anticipated alcohol consumption. Results indicate that the modified IAT is associated with binge drinking episodes, perceived difficulty controlling alcohol use, and appetitive responses to alcohol cues. Findings are discussed in terms of the potential value of this measure to assess alcohol-related memory associations among those whose alcohol use puts them at risk for harm.