McClernon FJ, Kozink RV, Lutz AM, Rose JE. 24-h smoking abstinence potentiates fMRI-BOLD activation to smoking cues in cerebral cortex and dorsal striatum. Psychopharmacology (Berl) 204: 25-35

Duke University Medical Center Box 2701 Durham NC 27708 USA
Psychopharmacology (Impact Factor: 3.88). 05/2009; 204(1):25-35. DOI: 10.1007/s00213-008-1436-9

ABSTRACT RationaleExposure to smoking-related cues can trigger relapse in smokers attempting to maintain abstinence.

ObjectivesIn the present study, we evaluated the effect of 24-h smoking abstinence on brain responses to smoking-related cues using
functional magnetic resonance imaging (fMRI).

Materials and methodsEighteen adult smokers underwent fMRI scanning following smoking as usual (satiated condition) and following 24-h abstinence
(abstinent condition). During scanning, they viewed blocks of photographic smoking and control cues.

ResultsFollowing abstinence, greater activation was found in response to smoking cues compared to control cues in parietal (BA 7/31),
frontal (BA 8/9), occipital (BA 19), and central (BA 4) cortical regions and in dorsal striatum (putamen) and thalamus. In
contrast, no smoking cue greater than control cue activations were observed following smoking as usual. Direct comparisons
between conditions (satiated vs. abstinent) showed greater brain reactivity in response to smoking cues following abstinence.
In addition, positive correlations between pre-scan craving in the abstinent condition and smoking cue activation were observed
in right dorsomedial prefrontal cortex (dmPFC) including superior frontal gyrus (BA 6/10), anterior cingulate gyrus (BA 32),
and supplementary motor area (BA 6).

ConclusionsThe present findings indicate that smoking abstinence significantly potentiates neural responses to smoking-related cues in
brain regions subserving visual sensory processing, attention, and action planning. Moreover, greater abstinence-induced craving
was significantly correlated with increased smoking cue activation in dmPFC areas involved in action planning and decision
making. These findings suggest that drug abstinence can increase the salience of conditioned cues, which is consistent with
incentive-motivation models of addiction.

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Available from: Francis Joseph McClernon, Sep 25, 2015
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    • "Despite these limitations, CR studies have yielded findings indicating that smokers (and other drug users) react to smoking/drug cues (Carter and Tiffany, 1999), that such responses are reproducible (LaRowe et al., 2007), that some smokers react more strongly than others (Shiffman et al., 2003), and that these individual differences are sometimes (but not consistently) correlated with other variables of interest (Abrams et al., 1988; Powell et al., 2010; Waters et al., 2004; Watson et al., 2010). This has been seen not only for subjective measures of craving, but also for objective measures such as changes in regional brain activity (Engelmann et al., 2012; Janes et al., 2010; McClernon et al., 2009). This suggests that CR studies are measuring something, even if they are not representing real-world reaction to particular cues. "
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    ABSTRACT: Laboratory cue reactivity (CR) assessments are used to assess smokers' responses to cues. Likewise, EMA recording is used to characterize real-world response to cues. Understanding the relationship between CR and EMA responses addresses the ecological validity of CR. In 190 daily smokers not currently quitting, craving and smoking responses to cues were assessed in laboratory CR and by real-world EMA recording. Separate CR sessions involved 5 smoking-relevant cues (smoking, alcohol, negative affect, positive affect, smoking prohibitions), and a neutral cue. Subjects used EMA to monitor smoking situations for 3 weeks, completing parallel situational assessments (presence of others smoking, alcohol consumption, negative affect, positive affect, and smoking prohibitions, plus current craving) in smoking and non-smoking occasions (averaging 70 and 60 occasions each). Analyses correlated CR craving and smoking cue responses with EMA craving and smoking correlations with similar cues. Although some cues did not show main effects on average craving or smoking, a wide range of individual differences in response to cues was apparent in both CR and EMA data, providing the necessary context to assess their relationship. Laboratory CR measures of cue response were not correlated with real-world cue responses assessed by EMA. The average correlation was 0.03; none exceeded 0.32. One of 40 correlations examined was significantly greater than 0. Laboratory CR measures do not correlate with EMA-assessed craving or smoking in response to cues, suggesting that CR measures are not accurate predictors of how smokers react to relevant stimuli in the real world. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Drug and alcohol dependence 07/2015; 155. DOI:10.1016/j.drugalcdep.2015.07.673 · 3.42 Impact Factor
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    • "Heavy smokers significantly inhibited the startle reflex in response to tobacco-related cues compared with light smokers (Cui et al. 2012). Twenty-four hour abstinence periods increased the startle reflex to tobacco-related cues (McClernon et al. 2009), whereas abstinence periods of 12 h or less have shown mixed results (Cinciripini et al. 2006; McBride et al. 2006; McClernon et al. 2005). Few studies have explored the influence of motivation to change on modulation of the startle reflex in smokers with low and high motivation to change (Dempsey et al. 2007; Muñoz et al. 2011); but not in ex-smokers, these results provide a better understanding of the changes in the motivational response through the entire process of change. "
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    ABSTRACT: Studies that have investigated the effect of motivation to change on the startle reflex have been limited to comparisons among smokers with low and high motivation, but differences in the startle reflex throughout all stages of change have not been studied. Therefore, the aim of the present study was to identify differences in the startle reflex in response to tobacco-related cues in smokers in the initial, intermediate, and final stages of change. The startle reflex was recorded in 67 smokers and ex-smokers while they viewed pleasant, neutral, unpleasant, and tobacco-related pictures. The results showed that the pattern of the startle reflex in response to tobacco-related pictures varied according to the motivation to change. In smokers in the initial stages, the magnitude of the startle reflex was similar between tobacco-related pictures and pleasant pictures. In smokers in intermediate stages, the magnitude of the startle reflex was similar between tobacco-related pictures and unpleasant pictures. In ex-smokers in the final stages, the magnitude of the startle reflex was similar between tobacco-related pictures and neutral pictures. These results suggest that motivational systems that are activated by tobacco-related cues vary according to smokers’ motivation to change.
    Motivation and Emotion 03/2015; 39(2):293-298. DOI:10.1007/s11031-014-9449-7 · 1.55 Impact Factor
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    • "Of utmost importance, limbic activation and inception of craving following the presentation of drug cues are relatively independent of a pharmacological abstinence state and may also be elicited after drug administration (Franklin et al., 2007). Moreover , abstinence and withdrawal states may potentiate cue-induced craving in the PFC and striatum (McClernon et al., 2008). Studies using positron emission tomography (PET) imaging, which allows the imaging of a radioactive compound acting as a competitive agonist to certain receptors, have shown that cocaine-and nicotine-related cues induce changes in metabolic activity in the striatum, ACC, and different regions of the PFC (Brody et al., 2002; Volkow et al., 2007). "
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    ABSTRACT: Craving is recognized as an important diagnosis criterion for substance use disorders (SUDs) and a predictive factor of relapse. Various methods to study craving exist; however, suppressing craving to successfully promote abstinence remains an unmet clinical need in SUDs. One reason is that social and environmental contexts recalling drug and alcohol consumption in the everyday life of patients suffering from SUDs often initiate craving and provoke relapse. Current behavioral therapies for SUDs use the cue-exposure approach to suppress salience of social and environmental contexts that may induce craving.They facil- itate learning and cognitive reinforcement of new behavior and entrain craving suppression in the presence of cues related to drug and alcohol consumption. Unfortunately, craving often overweighs behavioral training especially in real social and environmental contexts with peer pressure encouraging the use of substance, such as parties and bars. In this perspective, virtual reality (VR) is gaining interest in the development of cue-reactivity par- adigms and practices new skills in treatment. VR enhances ecological validity of traditional craving-induction measurement. In this review, we discuss results from (1) studies using VR and alternative virtual agents in the induction of craving and (2) studies combining cue- exposure therapy with VR in the promotion of abstinence from drugs and alcohol use. They used virtual environments, displaying alcohol and drugs to SUD patients. Moreover, some environments included avatars. Hence, some studies have focused on the social interac- tions that are associated with drug-seeking behaviors and peer pressure. Findings indicate that VR can successfully increase craving. Studies combining cue–exposure therapy with virtual environment, however, reported mitigated success so far.
    Frontiers in Human Neuroscience 10/2014; 8(1):1-15. DOI:10.3389/fnhum.2014.00844/abstract · 2.99 Impact Factor
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