Neuroimaging of situational urgency and incontinence provoked by personal urgency cues.

INTRODUCTION: Situational triggers for urinary urgency and incontinence (UUI) such as "latchkey incontinence" and running water are often reported clinically, but no current clinical tools exist to directly address symptoms of UUI provoked by environmental stimuli. Previously we have shown that urgency and leakage can be reproduced during urodynamic studies with exposure to personal urgency-related images. Here we investigate the neural signatures associated with such situational triggers to inform potential therapies for reducing reactivity to these personal urgency-related cues among women with situational UUI. METHOD: We recruited 23 women with situational UUI who took photographs of their personal "urgency trigger" and "safe" situations and were exposed to them in a magnetic resonance imaging (MRI) scanner. We identified brain areas that were more active during urgency versus safe image exposure. RESULTS: We found that, during urgency image exposure, main components of the attention network and decision-related processes, the middle and medial frontal gyri, were more active (p < 0.01). In addition, areas well known to be involved in the continence mechanism, such as the cingulate and parahippocampal areas, were also more active during urgency image exposure. CONCLUSION: Exposure to personal situational urgency images activated different areas of the brain compared with safe environments, highlighting the complex brain mechanisms that provoke real-world urgency. Using brain and behavioral-based therapies which target the attentional areas identified here and extinguish cue reactivity might reduce symptom burden in this subset of UUI sufferers.

Reproducing situationally triggered urgency incontinence in a controlled environment.

INTRODUCTION: Patients with lower urinary tract symptoms often report urgency and incontinence episodes which are triggered by environmental scenarios, for example, "latch-key incontinence." To better understand the extent of this phenomenon, and how best to reduce its impact, we tested ways to recreate these situational cues in a controlled environment and obtain cue reactivity measures. METHODS: We developed a standardized set of urgency cue scenarios from interviews with sufferers of situational urgency urinary incontinence (UUI), personalized urgency, and safe cue sets consisting of photographs of specific locations, and measurements of cue reactivity during computer-based presentation and urodynamic monitoring. RESULTS: Common urgency and safe cues were identified for the standardized cue set. Exposure to these standardized cues elicited change in bladder sensation in 7 of 12 participants. Participants created personalized cue sets with photographs depicting their own urgency triggering scenarios; exposure to personalized cue photos elicited change in sensation in 11 of 12 participants. In addition, personalized cues elicited measurable detrusor overactivity and leakage during urodynamic monitoring. Safe cues reduced bladder sensation in five participants. CONCLUSION: We developed a computer-based means of displaying cue photos which elicited cue reactivity from women suffering from situational urgency incontinence. Cue reactivity was increased by personalizing photos of cue scenarios and obtaining physiological measures from urodynamics. We have developed an appropriate way to test cue reactivity in women with situational UUI.

Combined Smoking Cues Enhance Reactivity and Predict Immediate Subsequent Smoking.

Introduction: Cue reactivity (CR) research has reliably demonstrated robust cue-induced responding among smokers exposed to common proximal smoking cues (eg, cigarettes, lighter). More recent work demonstrates that distal stimuli, most notably the actual environments in which smoking previously occurred, can also gain associative control over craving. In the real world, proximal cues always occur within an environment; thus, a more informative test of how cues affect smokers might be to present these two cue types simultaneously. Methods: Using a combined-cue counterbalanced CR paradigm, the present study tested the impact of proximal (smoking and neutral) + personal environment (smoking and nonsmoking places) pictorial cues, on smokers' subjective and behavioral CR; as well as the extent to which cue-induced craving predicts immediate subsequent smoking in a within-subjects design. Results: As anticipated, the dual smoking cue combination (ProxS + EnvS) led to the greatest cue-induced craving relative to the other three cue combinations (ProxS + EnvN, ProxN + EnvS, and ProxN ± EnvN), ps < .004. Dual smoking cues also led to significantly shorter post-trial latencies to smoke, ps < .01. Overall CR difference score (post-trial craving minus baseline craving) was predictive of subsequent immediate smoking indexed by: post-trial latency to smoke [B = -2.69, SE = 9.02; t(143) = -2.98, p = .003]; total puff volume [B = 2.99, SE = 1.13; t(143) = 2.65, p = .009]; and total number of puffs [B = .053, SE = .027; t(143) = 1.95, p = .05]. Conclusions: The implications of these findings for better understanding the impact of cues on smoking behavior and cessation are discussed. Implications: This novel cue reactivity study examined smokers' reactivity to combined proximal and distal smoking cues. Exposure to a combination of two smoking cues (proximal and environment) led to the greatest increases in cue-induced craving and smoking behavior compared to all other cue combinations. Further, the overall magnitude of cue-induced craving was found to significantly predict immediate subsequent smoking. This work provides new insight on how exposure to various cues and cue combinations directly affect smokers' craving and actual smoking behavior, as well as the relationship between those two indices of reactivity.

Initial Evaluation of Fenofibrate for Efficacy in Aiding Smoking Abstinence.

INTRODUCTION: Primate and rodent models show that peroxisome proliferator-activated receptor-alpha (PPAR-α) ligands, including fibrate medications, reduce nicotine reinforcement, reward, and related effects. We tested fenofibrate, the most common U.S. Food and Drug Administration-approved fibrate for lipid control versus placebo for initial evidence of efficacy in smoking cessation using a validated cross-over procedure for early Phase 2 evaluations. METHODS: Adult dependent smokers (N = 38) in this 4-week within-subjects study were those already intending to try to quit in the next 2 months. All smoked ad libitum during weeks 1 (baseline) and 3 (washout) and began fenofibrate (160 mg/d; dosing approved for lipid control) or placebo near the end of weeks 1 and 3. Following each 4-day dose run-up, they were then instructed to try to quit for 4 days (Tuesday-Friday) during weeks 2 and 4, with the order of medication conditions counter-balanced and administered double-blind. Abstinence was verified daily in each 4-day quit period by self-report of no smoking in the prior 24 hours and carbon monoxide < 5 ppm. Secondary measures of acute smoking reinforcement and cue reactivity prior to quitting, and smoking reduction when trying to quit, were also assessed. RESULTS: No differences between fenofibrate versus placebo were found on days quit (means ± SEM of 1.8±0.3 vs. 1.9±0.3, respectively). Similarly, there were no differences in any of the secondary measures (all P > .20). CONCLUSIONS: Although higher dosing or other proliferator-activated receptor-alpha agonists may show efficacy, this study indicates that fenofibrate does not aid ability to stop smoking during a brief practice quit period in dependent smokers high in current quit interest.

Do people serve as cues to smoke?

INTRODUCTION: Recent research has identified that the environments in which smoking has previously occurred can alone, in the absence of any explicit smoking stimuli (e.g., cigarettes, lighters), serve as cues that induce robust craving to smoke. The goal of the present study was to determine if people can similarly function as smoking and nonsmoking cues capable of directly affecting smokers' cue-induced craving. METHODS: Smokers (N = 72) borrowed cameras to take photos of the people in their lives around whom they do and do not smoke ("personal" smoking and nonsmoking people, PS and PN, respectively). Self-report and physiological cue reactivity to those photos were compared with smokers' reactivity to photos of people unknown to them ("standard" smoking and nonsmoking people, SS and SN, respectively). RESULTS: Results suggest that the people around whom smokers regularly smoke (PS) can alone function as cues capable of eliciting patterns of reactivity similar to that evoked by proximal and environment smoking cues, namely, increased craving to smoke, negative affect, and excitement. In contrast, the people around whom smokers do not smoke become associated with not smoking (PN) and serve a potential protective function by reducing craving and increasing calm. CONCLUSIONS: This novel investigation and its results have implications for promoting smoking cessation by developing strategies to manage a smoker's social environment.

Smoking in response to negative mood in men versus women as a function of distress tolerance.

INTRODUCTION: Negative mood situations often increase smoking behavior and reward, effects that may be greater among women and smokers low in tolerance for distress. METHODS: Adult dependent smokers (N = 164; 86 men, 78 women) first completed measures of distress tolerance via self-report and by mirror-tracing and breath-holding tasks. They then participated in 2 virtually identical laboratory sessions, involving induction of negative versus neutral mood (control) via pictorial slides and music. They rated negative affect (NA) before and during mood induction and smoked their preferred brand ad libitum during the last 14 min of mood induction. Our aim was to examine mood effects on NA, smoking reward ("liking"), and smoking intake (puff volume and number) as a function of sex and distress tolerance. RESULTS: Negative mood induction increased NA, as planned, and smoking reward and intake compared with neutral mood. Increases in NA and puff volume due to negative mood were greater in women compared with men, as hypothesized, but no main effects of the self-report or behavioral distress tolerance measures were seen in responses to mood induction. However, unexpectedly, lower self-reported distress tolerance was associated with greater smoking intake due to negative (but not neutral) mood in men and generally due to neutral (but not negative) mood in women. CONCLUSIONS: Negative mood may increase smoking intake more in women compared with men. Yet, low distress tolerance may enhance smoking intake due to negative versus neutral mood differentially between women and men, suggesting that sex and distress tolerance may interact to influence smoking responses to negative mood.

The reliability of puff topography and subjective responses during ad lib smoking of a single cigarette.

INTRODUCTION: Acute smoking behavior (i.e., puff topography) and subjective responses during the ad lib smoking of a single cigarette in the laboratory may provide useful measures of smoking reinforcement and reward, respectively. However, the reliability of such measures is not clear, leaving uncertain the utility of a single assessment of smoking behavior as an individual difference measure. METHODS: Dependent smokers (N = 94) smoked normally prior to each of 4 laboratory sessions during which they were instructed to smoke 1 cigarette of their preferred brand in ad libitum and unblinded fashion and then rate it for subjective effects. Puff topography (puff number, total volume, and maximum volume) was assessed via portable Clinical Research Support System device. Subjective reward and perception were assessed by visual analog scales of "liking" and "how strong," respectively. The reliability of puff topography and subjective measures was determined across days by intra-class correlations (ICCs). Differences due to sex and nicotine dependence (high and low Fagerström Test for Nicotine Dependence score) were also examined. RESULTS: Reliability was highly significant for each measure. ICCs were .70 for total puff volume, .60 for maximum puff volume, .73 for puff number, .64 for liking, and .78 for how strong. Reliability generally did not differ by sex or dependence, but absolute values for total volume and maximum puff volume were greater in men and in high dependent smokers. Liking was also greater in high dependent smokers. CONCLUSIONS: Puff topography and subjective measures during the ad lib smoking of a single cigarette are highly reliable. Smoking responses during a single ad lib smoking session may be useful in identifying stable individual differences in smoking reinforcement and reward.

Smokers' Self-Report and Behavioral Reactivity to Combined Personal Smoking Cues (Proximal + Environment + People): A Pilot Study.

Cue reactivity (CR) among smokers exposed to smoking-related stimuli, both proximal (e.g., cigarettes, lighter) and distal (environments, people), has been well-demonstrated. Furthermore, past work has shown that combining proximal smoking cues with smoking environment cues increases cue-provoked craving and smoking behavior above that elicited by either cue type alone. In this pilot study, we examined the impact of combining three personal cues, proximal + environment + people, on subjective and behavioral cue reactivity among smokers. To further understand the impact of this method, we also tested reactivity under the conditions of both smoking satiety and deprivation. In addition, we examined the extent to which cue-induced craving predicted immediate subsequent smoking. Fifteen smokers completed six sessions, of which two focused on the intake and development of personal cues and four involved personal cue reactivity sessions: (1) deprived, smoking cue combination, (2) deprived, nonsmoking cue combination, (3) sated, smoking combination, and (4) sated, nonsmoking cue combination. Cue-provoked craving was greater and smokers were quicker to light a cigarette and smoked more during their exposure to smoking rather than nonsmoking cues and in deprived compared to sated conditions, with no interaction between these variables. While deprived, greater cue-provoked craving in response to smoking cues was correlated with a quicker latency to light a cigarette. This work supports the feasibility of presenting three personal smoking-related combinations of cues within a cue reactivity paradigm and highlights the robust reactivity that this methodology can evoke in smokers.

Can exercise alleviate sleep disturbances during acute nicotine withdrawal in cigarette smokers?

Sleep disturbances, including insomnia (difficulty falling or staying asleep), are common nicotine withdrawal symptoms particularly during the initial stage of nicotine abstinence, and increase the likelihood of relapse within the first 4 weeks of quitting. Although clinically recognized as a key symptom of nicotine withdrawal, sleep disturbances are not addressed in the clinical guidelines for nicotine dependence treatment. Unfortunately, Nicotine Replacement Therapy (NRT) and other pharmacologic interventions do not attenuate withdrawal-provoked sleep disturbances, with several even exacerbating sleep disruption. The present study tested the impact of 30-min of daily moderate exercise, morning versus evening, on key polysomnographic indicators of sleep disturbances during initial 3 days (72 hr) of nicotine withdrawal. Forty-nine daily smokers (53% male) completed 3 separate abstinence periods, during which they completed either morning exercise, evening exercise, or a nonexercising magazine reading control condition. Order of condition was counterbalanced across subjects with a 1-week wash out in between each 3-day abstinence period. Exercise engagement mitigated several changes in sleep architecture associated with acute nicotine deprivation and other time-related effects on sleep, specifically frequency of arousals (B = -2.8, SE = .95; t(1271) = -3.0, p = .003) and reductions in sleep maintenance (B = .58, SE = .21; t(1270) = 2.8, p = .005). Additionally, smokers who reported greater perceived withdrawal severity had the longest latency to fall asleep but experienced the greatest attenuation of this effect following PM exercise. Overall, results suggest a role for exercise as an adjunct smoking cessation treatment to specifically target sleep disturbances during early acute nicotine withdrawal. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Exposure to attachment figure cue reduces cigarette craving.

Cue-induced craving among smokers is a well-documented phenomenon. Conditioning theory is used to explain how stimuli elicit cravings. Attachment theory may explain additional influences on cue-induced craving. This study tested the effects of cigarette cues and attachment figure cues on craving and affect. Cue-reactivity as a function of cue type was examined to explore the magnitude of craving effect sizes for each cue type. Thirty-six smokers (27 men) were exposed to cigarette cues (i.e., cigarette) and attachment figure cues (i.e., digital photos of people identified as attachment figures). Neutral to cue exposure differences in craving and affect were assessed. Sixty-one percent of participants reported increased craving to the cigarette cue (M = 61.1, SD = 29.4) compared to the neutral cue (M = 46.6, SD = 28.8), Mdiff = 20.7 (10.60, 30.73), Yt (23) = 4.24, p = .0003. When exposed to an attachment figure photo, 56% participants reported decreased craving (M = 38.2, SD = 31.6) compared to the neutral photo (M = 50.9, SD = 29.8), Mdiff = -15.73 (-30.83, -0.63), Yt (21) = -2.17, p = .042. There was a significant difference in the craving for cigarette cues (M = 14.5, SD = 22.8 (CI: 6.94, 22.39)), and attachment figure photos (M = -12.7, SD = 28.6 (CI: -22.38, -3.01); t(35) = 4.3, p < .001). The effect sizes for cigarette cues and attachment figure photos were d = .50, d = .42, respectively. Participants' responses to attachment cues were not influenced by their reactivity to cigarette cues or their attachment figure's smoking status. Findings support a plausible model in which an attachment figure photo decreases craving via affect regulation. Further research on cues that have an inhibitory effect on craving may inform new cessation strategies. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Mood, nicotine, and dose expectancy effects on acute responses to nicotine spray.

INTRODUCTION: We recently showed effects of nicotine dose and nicotine expectancy on some responses to cigarette smoking, with generally no influence of induced mood on these effects. The present study extended this line of research to Nicotrol nasal spray, to determine whether formulation (spray vs. smoking) alters responses. METHODS: Smokers abstained overnight before each of two virtually identical sessions, involving negative or positive mood induction. They were randomized to one of five groups, four comprising the 2 x 2 balanced placebo design, varying actual and expected dose of nicotine in the nasal spray, and the fifth group a no-spray control. Dependent measures included self-reported affect, craving, withdrawal, and spray ratings of "liking" and "how much nicotine." Analyses were limited to those whose nicotine expectancies were manipulated successfully (N = 48). RESULTS: The following results matched those from our smoking study: expecting nicotine increased liking; expected, but not actual, nicotine dose increased dose perception; neither actual nor expected nicotine dose had much influence on affect or withdrawal; and mood had no influence on these effects. However, both actual and expected nicotine dose decreased craving in response to spray, contrary to our prior study with smoking. DISCUSSION: Formulation made little difference in some effects of nicotine and expectancies, but other effects differed by formulation. Some of these findings, particularly for craving reduction, may have implications for enhancing the acute therapeutic effects of nasal spray and, perhaps, other medications in smokers trying to maintain abstinence after quitting.

Randomized Trial of Low-Nicotine Cigarettes and Transdermal Nicotine.

INTRODUCTION: A mandated reduction in the nicotine content of cigarettes may decrease smoking, but also increase demand for other nicotine products. The present study tested the impact of smoking cigarettes with very low nicotine content and concurrent use of a transdermal nicotine patch. STUDY DESIGN: A balanced 2 × 2 factorial randomized clinical trial investigating the impact of cigarette nicotine content (double-blind, very low nicotine content versus normal nicotine content) and use of a transdermal nicotine patch (open label, patch versus no patch). SETTING/PARTICIPANTS: Adult daily smokers (n=240) in the Pittsburgh, PA area. INTERVENTION: Participants were provided with research cigarettes and transdermal nicotine patches (if assigned to patch condition) for 7 weeks. Cigarettes were Spectrum brand (National Institute on Drug Abuse) and either 15.8 mg nicotine/g tobacco (normal nicotine content) or 0.4 mg nicotine/g tobacco (very low nicotine content). In the 7th week, participants were monetarily incentivized to abstain from smoking. MAIN OUTCOME MEASURES: Participants reported daily cigarette use throughout the trial and the primary outcome was average number of cigarettes smoked per day (study + nonstudy) during Week 6. Participants were recruited from 2015 to 2017 and data were analyzed between 2017 and 2018. RESULTS: Assignment to very low nicotine content cigarettes and assignment to wear a nicotine patch both reduced the number of cigarettes smoked per day during Week 6 (p=0.001 and 0.04, respectively). However, assignment to the patch along with very low nicotine content cigarettes did not significantly reduce cigarette smoking compared with assignment to very low nicotine content cigarettes alone. CONCLUSIONS: A mandated reduction in the nicotine content of cigarettes is likely to reduce the number of cigarettes smoked per day, but the added benefit of concurrent transdermal nicotine is unclear. Future studies should investigate whether alternative sources of noncombusted tobacco, such as e-cigarettes, enhance the effects of very low nicotine content cigarettes on smoking. TRIAL REGISTRATION: This study is registered at www.clinicaltrials.gov NCT02301325.

Mood influences on acute smoking responses are independent of nicotine intake and dose expectancy.

Acute responses to smoking are influenced by nicotine and by nonpharmacological factors such as nicotine dose expectancy and sensory effects of smoke inhalation. Because negative mood increases smoking reinforcement, the authors examined whether these effects may be altered by mood context. Smokers (n=200) participated in 2 sessions, negative or positive mood induction, and were randomized to 1 of 5 groups. Four groups comprised the 2x2 balanced placebo design, varying actual (0.6 mg vs. 0.05 mg yield) and expected nicotine dose (expected nicotine vs. denicotinized [denic]) of cigarettes. A fifth group was a no-smoking control. Smoking, versus not smoking, attenuated negative affect, as well as withdrawal and craving. Negative mood increased smoking reinforcement. However, neither actual nor expected nicotine dose had much influence on these responses; even those smokers receiving and expecting a denic cigarette reported attenuated negative affect. A follow-up comparison suggested that the sensory effects of smoke inhalation, but not the simple motor effects of smoking behavior, were responsible. Thus, sensory effects of smoke inhalation had a greater influence on relieving negative affect than actual or expected nicotine intake.

Proximal versus distal cues to smoke: the effects of environments on smokers' cue-reactivity.

Smokers are highly reactive to smoking-related cues that are directly linked, or most proximal, to actual smoking behavior (e.g., lit cigarettes). However, over the course of smoking, proximal cues may not be the only stimuli to become strongly associated with smoking. Distal cues, such as the environments in which smoking occurs (e.g., bar) might also gain associative properties and come to evoke robust reactivity from smokers. To test this, a pilot study was first conducted to develop standard pictorial stimuli of smoking and nonsmoking environments, all of which were completely devoid of proximal smoking cues. A comparison set of smoking and nonsmoking proximal cues was then created. Using the 12 total pictorial cues developed, 62 adult smokers participated in a cue-reactivity study during which they viewed and rated pictorial smoking and nonsmoking environment and proximal cues. Results demonstrate that, similar to proximal cues, environments associated with smoking can alone function as stimuli capable of evoking strong subjective reactivity from smokers. This work supports a broader conceptualization of drug-related cues in cue-based research and treatment development that includes proximal and distal cues as distinct categories. (PsycINFO Database Record (c) 2008 APA, all rights reserved).

Smoking environment cues reduce ability to resist smoking as measured by a delay to smoking task.

INTRODUCTION: Environments associated with smoking may promote lapse and relapse in smokers attempting to quit. Here we examined the effects of exposure to visual smoking environment cues on smoking urge and the ability to resist smoking, as measured with a delay-to-smoking task in which monetary contingencies are provided for resisting smoking. METHODS: Adult daily smokers (n=22) completed two experimental sessions, each following 6h smoking abstinence. Sessions differed only in the type of cue participants were exposed to (smoking environments vs. nonsmoking environments). Participants completed subjective ratings of smoking urge, withdrawal and other reactions (i.e. craving, affect). Behavioral outcomes on the delay-to-smoking task included latency to first cigarette, number of cigarettes smoked and average number of puffs per cigarette. RESULTS: Across cue exposure sessions, 64% of participants initiated smoking (no effect of condition was observed). However, exposure to smoking environments as compared to the nonsmoking environments resulted in greater craving, faster initiation of smoking, and more smoked cigarettes. Greater craving was associated with a shorter time to initiate smoking, but this effect did not differ across sessions. In contrast, withdrawal was more strongly associated with number of cigarettes smoked during smoking environment sessions. CONCLUSION: Together, these results suggest smoking environments increase smoking urge and promote smoking behavior. Further research is necessary to examine the specific and interactive effects of smoking-related environments on real-world smoking lapse and relapse.

Exercise attenuates negative effects of abstinence during 72 hours of smoking deprivation.

Exercise is presumed to be a potentially helpful smoking cessation adjunct reputed to attenuate the negative effects of deprivation. The present study examined the effectiveness of moderate within-session exercise to reduce 4 key symptoms of smoking deprivation during 3 72-hr nicotine abstinence blocks in both male and female smokers. Forty-nine (25 male, 24 female) sedentary smokers abstained from smoking for 3 consecutive days on 3 separate occasions. At each session, smokers' abstinence-induced craving, cue-induced craving, negative mood, and withdrawal symptom severity were assessed prior to and after either exercise (a.m. exercise, p.m. exercise) or a sedentary control activity (magazine reading). Abstinence-induced craving and negative mood differed as a function of condition, F(2, 385) = 21, p < .0001; and, F(2, 385) = 3.38, p = .03. Planned contrasts revealed no difference between a.m. and p.m. exercise, but exercise overall led to greater pre-post reduction in abstinence-induced craving, t(385) = 6.23, p < .0001, effect size Cohen's d = 0.64; and negative mood, t(385) = 2.25, p = .03, d = 0.23. Overall exercise also led to a larger pre-post reduction in cue-induced craving in response to smoking cues, F(2, 387) = 8.94, p = .0002; and withdrawal severity, F(2, 385) = 3.8, p = .02. Unlike the other 3 measures, p.m. exercise reduced withdrawal severity over control, t(385) = 2.64, p = .009, d = 0.27, whereas a.m. exercise did not. The results support the clinical potential of exercise to assist smokers in managing common and robust negative symptoms experienced during the first 3 days of abstinence. (PsycINFO Database Record

Environments as cues to smoke: implications for human extinction-based research and treatment.

Animal research has shown that the environments, or contexts, in which drug use occurs can play a key role in how animals respond to drug-related cues. Less is known about the role of environmental contexts in human drug-dependence research. Traditionally, cue-based studies and treatments focus on conditioned cues most proximal to drug administration (e.g., lit cigarettes, pictorial stimuli of drug paraphernalia). However, there is reason to believe that more distal cues, such as the environments in which drugs were previously used, might similarly gain associative control over human responding. This article describes a body of systematic research aimed at identifying and studying the impact of environmental contexts on smokers' cue reactivity in the laboratory. Overall, results of this program of research demonstrate that exposure to environments associated with smoking, but completely devoid of proximal smoking cues, can function as conditioned stimuli capable of evoking strong subjective responding from abstinent smokers. Furthermore, more robust reactivity can be achieved if environmental context cues are personalized using novel techniques described in this article.

Hippocampal and Insular Response to Smoking-Related Environments: Neuroimaging Evidence for Drug-Context Effects in Nicotine Dependence.

Environments associated with prior drug use provoke craving and drug taking, and set the stage for lapse/relapse. Although the neurobehavioral bases of environment-induced drug taking have been investigated with animal models, the influence of drug-environments on brain function and behavior in clinical populations of substance users is largely unexplored. Adult smokers (n=40) photographed locations personally associated with smoking (personal smoking environments; PSEs) or personal nonsmoking environment (PNEs). Following 24-h abstinence, participants underwent fMRI scanning while viewing PSEs, PNEs, standard smoking and nonsmoking environments, as well as proximal smoking (eg, lit cigarette) and nonsmoking (eg, pencil) cues. Finally, in two separate sessions following 6-h abstinence they viewed either PSEs or PNEs while cue-induced self-reported craving and smoking behavior were assessed. Viewing PSEs increased blood oxygen level-dependent signal in right posterior hippocampus (pHPC; F(2,685)=3.74, p<0.024) and bilateral insula (left: F(2,685)=6.87, p=0.0011; right: F(2,685)=5.34, p=0.005). In the laboratory, viewing PSEs, compared with PNEs, was associated with higher craving levels (F(2,180)=18.32, p<0.0001) and greater ad lib smoking (F(1,36)=5.01, p=0.032). The effect of PSEs (minus PNEs) on brain activation in right insula was positively correlated with the effect of PSEs (minus PNEs) on number of puffs taken from a cigarette (r=0.6, p=0.001). Our data, for the first time in humans, elucidates the neural mechanisms that mediate the effects of real-world drug-associated environments on drug taking behavior under conditions of drug abstinence. These findings establish targets for the development and evaluation of treatments seeking to reduce environment provoked relapse.

Subjective and reinforcing effects of smoking during negative mood induction.

Two notions strongly held by many smokers are that negative mood increases smoking behavior and that this increase is due to the ability of smoking to alleviate negative affect. This study used a modified mood induction procedure to examine both the impact of smoking on induced mood, as well as the effect of induced mood on actual smoking behavior. Forty-eight smokers were randomly assigned to a smoking or a water-drinking comparison group. Each participant attended 3 sessions during which 1 of 3 mood states (positive, negative, or neutral) was induced. Contrary to expectation, smoking did not attenuate negative affect. However, negative mood induction subsequently quickened latency to smoke and increased number of puffs consumed ad lib.

Examining the relationship between cue-induced craving and actual smoking.

Smoking cue-reactivity studies have consistently demonstrated heightened self-report craving, as well as moderate autonomic reactivity, among smokers exposed to salient drug-related cues. However, significantly fewer studies have examined whether exposure to smoking cues affects smokers' actual smoking, or examined the predictive relationship between cue-induced craving and smoking behavior. Using our well-tested pictorial cues in a cue-reactivity paradigm, we investigated the impact of smoking-related cues relative to neutral cues on subjective craving and smoking behavior (assessed via CReSS; Plowshare Technologies, Baltimore, MD) measures of latency to smoke, puff volume, and number of puffs). Further, we examined the predictive value of cue-induced craving on subsequent smoking behavior. Sixty nondeprived daily smokers completed 2 experimental sessions involving exposure to either smoking-related or neutral pictorial cues. Following initial exposure to cues, smokers rated their craving and were then allowed to smoke freely if they chose to during a subsequent 6-min cue exposure period. Result showed that exposure to smoking cues relative to neutral predicted significantly greater craving and increases in smoking behavior. Likewise, the magnitude of the difference in cue-induced craving when exposed to smoking cues relative to neutral cues (i.e., the cue-reactivity effect) was highly predictive of shorter latency to smoke, as well as increased number of puffs and puff volume.