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The U.S. Food and Drug Administration has the authority to regulate characteristics of electronic nicotine delivery systems (ENDS). Prior research indicates that regulation of certain characteristics of these products may have an effect on their appeal and use. Policies that affect appeal and use of ENDS are relevant to attempts to reduce use among young people-including young adults-but are also relevant to adults who use these products as harm reduction tools. Using a novel concurrent choice task, we evaluated the relative reinforcement of JUUL brand ENDS products that varied in flavor (n = 8) and nicotine (n = 8) among samples of young adults who use JUUL. Findings suggest that restricting JUUL flavor to tobacco-only results in decreased appeal, while reducing the nicotine content of JUUL pods to 3%-from the conventional 5%-does not have an effect on product appeal. Findings also validate a novel methodology for delivering fixed doses of ENDS vapor within the context of a task that assesses the relative reinforcement of ENDS products with varying characteristics. This methodology can be applied to assessing the relative reinforcing effects of a wide variety of tobacco products with varied characteristics. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

INTRODUCTION: The aim of this pilot study was to assess young adult dual e-cigarette (EC) and combustible cigarette (CC) users’ anticipated responses to hypothetical market restrictions regarding key e-cigarette characteristics. METHODS: Data came from 240 young adult dual EC and CC users recruited via Amazon Mechanical Turk in June 2017. Descriptive statistics were used to report sociodemographic, CC smoking, and EC use characteristics. McNemar’s chi-square tests and chi-square tests were used to assess differences between groups in terms of anticipated responses to hypothetical EC market restrictions. RESULTS: Hypothetical regulations resulted in reported intentions to reduce EC use and increase CC use; the greatest impact was found for restrictions regarding e-liquid nicotine content, followed by flavor and ability to modify EC devices. Moreover, individuals reporting use of flavored e-liquid, high nicotine content e-liquid, and customizable EC were most likely to report intentions to reduce EC use and increase CC use. CONCLUSIONS: This work provides preliminary evidence that restrictive regulations regarding key EC characteristics may increase intentions to increase CC use among young adult dual EC and CC users.

In the United States, the Food and Drug Administration (FDA) has initiated a public dialogue about reducing the nicotine content of cigarettes. A reduced-nicotine standard could increase withdrawal symptoms among current smokers. We examined the impact of switching smokers to cigarettes that varied in nicotine content on withdrawal symptoms over 6 weeks. A secondary analysis (N = 839) of a 10-site, double-blind clinical trial of nontreatment-seeking smokers was completed. Participants were instructed to smoke study cigarettes, containing 0.4 to 15.8 mg of nicotine/g of tobacco, for 6 weeks and were then abstinent overnight. Using latent growth curves, trajectories of individual withdrawal symptoms were compared between the reduced nicotine content (RNC) conditions and a normal nicotine content (NNC) condition. Path analyses compared symptoms after overnight abstinence. Relative to NNC cigarettes, participants smoking RNC cigarettes had increased anger/irritability/frustration and increased appetite/weight gain during the initial weeks, but the symptoms resolved by Week 6. Individuals who were biochemically verified as adherent with using only the 0.4 mg/g cigarettes had higher sadness levels (Cohen's d = .40) at Week 6 compared with the NNC condition, although symptoms were mild. After a post-Week 6 overnight abstinence challenge, some RNC conditions relative to NNC condition exhibited reduced withdrawal. Individuals who were biochemically confirmed as adherent to the lowest nicotine condition experienced only mild and transient symptom elevations. Thus, a reduced-nicotine standard for cigarettes produced a relatively mild and temporary increase in withdrawal among nontreatment-seeking smokers (ClinicalTrials.gov No. NCT01681875). (PsycINFO Database Record

Smoking withdrawal negatively impacts inhibitory control, and these effects are greater for smokers with preexisting attention problems, such as attention deficit/hyperactivity disorder (ADHD). The current study preliminarily evaluated changes in inhibitory control-related behavior and brain activation during smoking withdrawal among smokers with ADHD. Moreover, we investigated the role of catecholamine transmission in these changes by examining the effects of 40 mg methylphenidate (MPH) administration. Adult daily smokers with (n=17) and without (n=20) ADHD completed fMRI scanning under each of three conditions: (a) smoking as usual+placebo; (b) 24 h smoking abstinence+placebo and (c) 24 h smoking abstinence+MPH. Scan order was randomized and counterbalanced. Participants completed a modified Go/No-Go task to assess both sustained and transient inhibitory control. Voxelwise analysis of task-related BOLD signal revealed a significant group-by-abstinence interaction in occipital/parietal cortex during sustained inhibition, with greater abstinence-induced decreases in activation observed among ADHD smokers compared with non-ADHD smokers. Changes in behavioral performance during abstinence were associated with changes in activation in regions of occipital and parietal cortex and bilateral insula during sustained inhibition in both groups. MPH administration improved behavioral performance and increased sustained inhibitory control-related activation for both groups. During transient inhibition, MPH increased prefrontal activation for both groups and increased striatal activation only among ADHD smokers. These preliminary findings suggest that abstinence-induced changes in catecholamine transmission in visual attention areas (eg, occipital and superior parietal cortex) may be associated with inhibitory control deficits and contribute to smoking vulnerability among individuals with ADHD.

Cigarette pack graphic warning labels (GWLs) are associated with increased knowledge of tobacco-related harms, scant research has evaluated their effects on behavior among vulnerable populations. We used a behavioral economic approach to measure the effects of GWLs and price on hypothetical cigarette purchasing behavior among HIV-positive smokers. Participants (n = 222) completed a cigarette valuation task by making hypothetical choices between GWL cigarette packs at a fixed price ($7.00) and text-only warning label cigarette packs at increasing prices ($3.50 to $14.00, $0.25 increments). More than one-quarter (28.8%) of participants paid more to avoid GWLs. The remaining participants&rsquo, purchasing decisions appear to have been driven by price: 69.8% of participants chose the cheaper pack. Across all participants, overall monetary choice value observed for GWL cigarette packs (mean = $7.75) was greater than if choice was driven exclusively by price ($7.00). Most (87.4%) preferred the text-only warning label when GWL and text-only cigarette packs were equally priced. Correlation analysis indicated GWL pack preference was associated with agreement with statements that GWLs would stop individuals from having a cigarette or facilitate thoughts about quitting. These data suggest that GWLs may influence some HIV-positive smokers in such a way that they are willing to pay more to void seeing GWLs.

The urinary metabolites cyanoethyl mercapturic acid (CEMA) and 3-hydroxypropyl mercapturic acid (3-HPMA) have been widely used as biomarkers of exposure to acrylonitrile and acrolein, respectively, but there are no published data on their consistency over time in the urine of cigarette smokers. We provided, free of charge over a 20 week period, Spectrum NRC600/601 research cigarettes to cigarette smokers in the control arm of a randomized clinical trial of the reduced nicotine cigarette. Urine samples were collected at weeks 4, 8, 12, 16, and 20 and analyzed for CEMA and 3-HPMA, and total nicotine equivalents (TNE) using validated methods. Creatinine-corrected intra-class correlation coefficients for CEMA, 3-HPMA, and TNE were 0.67, 0.46, and 0.68, respectively, indicating good longitudinal consistency for CEMA, while that of 3-HPMA was fair. A strong correlation between CEMA and TNE values was observed. These data support the use of CEMA as a reliable biomarker of tobacco smoke exposure. This is the first report of the longitudinal stability of the biomarkers of acrylonitrile and acrolein exposure in smokers. The data indicate that CEMA, the biomarker of acrylonitrile exposure, is consistent over time in cigarette smokers, supporting its use. While 3-HPMA levels were less stable over time, this biomarker is nevertheless a useful monitor of human acrolein exposure because of its specificity to this toxicant.

Food image fMRI paradigms are used widely for investigating the neural basis of ingestive behavior. However, these paradigms have not been validated in terms of ingestive behavior constructs, engagement of food-relevant neural systems, or test-retest reliability, making the generalizability of study findings unclear. Therefore, we validated the Macronutrient Picture System (MaPS) (McClernon et al., 2013), which includes food images from the six categories represented in the Geiselman Food Preference Questionnaire (FPQ) (Geiselman et al., 1998). Twenty-five healthy young adults (n = 21 female, mean age = 20.6 ± 1.1 years, mean BMI = 22.1 ± 1.9 kg/m2) rated the MaPS images in terms of visual interest, appetitive quality, nutrition, emotional valence, liking, and frequency of consumption, and completed the FPQ. In a second study, 12 individuals (n=8 female, mean age = 25.0 ± 6.5 years, mean BMI = 28.2 ± 8.7 kg/m2) viewed MaPS and control images (vegetables and non-food) during two separate 3T BOLD fMRI scans after fasting overnight. Intuitively, high fat/high sugar (HF/HS) and high fat/high complex carbohydrate (HF/HCCHO) images achieved higher liking and appetitive ratings, and lower nutrition ratings, than low fat/low complex carbohydrate/high protein (LF/LCHO/HP) images on average. Within each food category, FPQ scores correlated strongly with MaPS image liking ratings (p < 0.001). Brain activation differences between viewing images of HF/HS and vegetables, and between HF/HCCHO and vegetables, were seen in several reward-related brain regions (e.g., putamen, insula, and medial frontal gyrus). Intra-individual, inter-scan agreement in a summary measure of brain activation differences in seven reward network regions of interest was high (ICC = 0.61), and was even higher when two distinct sets of food images with matching visual ratings were shown in the two scans (ICC = 0.74). These results suggest that the MaPS provides valid representation of food categories and reliably activates food-reward-relevant neural systems.

Given that the vast majority of functional magnetic resonance imaging (fMRI) studies of drug cue reactivity use unisensory visual cues, but that multisensory cues may elicit greater craving-related brain responses, the current study sought to compare the fMRI BOLD response to unisensory visual and multisensory, visual plus odor, smoking cues in 17 nicotine-dependent adult cigarette smokers. Brain activation to smoking-related, compared to neutral, pictures was assessed under cigarette smoke and odorless odor conditions. While smoking pictures elicited a pattern of activation consistent with the addiction literature, the multisensory (odor + picture) smoking cues elicited significantly greater and more widespread activation in mainly frontal and temporal regions. BOLD signal elicited by the multi-sensory, but not unisensory cues, was significantly related to participants’ level of control over craving as well. Results demonstrated that the co-presentation of cigarette smoke odor with smoking-related visual cues, compared to the visual cues alone, elicited greater levels of craving-related brain activation in key regions implicated in reward. These preliminary findings support future research aimed at a better understanding of multisensory integration of drug cues and craving.

Why do people gamble? Conventional views hold that gambling may be motivated by irrational beliefs, risk-seeking, impulsive temperament, or dysfunction within the same reward circuitry affected by drugs of abuse. An alternate, unexplored perspective is that gambling is an extension of natural foraging behavior to a financial environment. However, when these foraging algorithms are applied to stochastic gambling outcomes, undesirable results may occur. To test this hypothesis, we recruited participants based on their frequency of gambling – yearly (or less), monthly, and weekly – and investigated how gambling frequency related to irrational beliefs, risk-taking/impulsivity, and foraging behavior. We found that increased gambling frequency corresponded to greater gambling-related beliefs, more exploratory choices on an explore/exploit foraging task, and fewer points earned on a patchy foraging task. Gambling-related beliefs negatively related to performance on the patchy foraging task, indicating that individuals with more gambling-related cognitions tended to leave a patch too quickly. This indicates that frequent gamblers have reduced foraging ability to maximize rewards; however, gambling frequency- and by extension, poor foraging ability- was not related to risk-taking or impulsive behavior. These results suggest that gambling reflects the application of a dysfunctional foraging process to financial outcomes.

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

Cue-elicited reactivity is a significant factor in relapse during smoking quit attempts. Previous research has focused primarily on visual smoking cues, with very limited research examining reactivity to olfactory triggers. Twenty-six adult non-treatment-seeking, nicotine-dependent smokers were exposed to 7 odorants during a cue-reactivity session measuring heart rate, skin conductance, and subjective craving. Cues included 2 cigarette odors (fresh tobacco and cigarette smoke), 2 odors previously identified as smoking-related (freshly mowed grass and coffee), 2 odors previously identified as unrelated to smoking (lavender and burned rubber), and 1 odorless control (propylene glycol). Pairwise comparisons demonstrated that subjective intensity of craving was significantly higher following exposure to the fresh tobacco odor compared with the odorless control (p < .01). A significant main effect for cue type on a physiological measure of arousal was also revealed, with a fresh tobacco odor-elicited significant increase in skin conductance level compared with the odorless control. However, no main effect of cue type on heart rate was found (p = .25). The results of the present study indicate that cigarette odor is an effective olfactory cue that heightens both subjective craving and increases skin conductance in smokers. Future research is needed to evaluate whether avoidance of these odors, or extinction of responses to them, can reduce relapse risk during smoking quit attempts.

INTRODUCTION: Techniques employed in the field of neuroscience, such as eye tracking, electroencephalography, and functional magnetic resonance imaging, have been important in informing our understanding of the cognitive mechanisms underlying tobacco smoking. These techniques are now increasingly being used to investigate the likely impact of tobacco control policies. AIMS AND METHODS: In this narrative review, we outline the value of these methodological approaches in answering policy-relevant tobacco control research questions, with a particular focus on their use in examining the impact of standardized cigarette packaging and health warnings. We also examine the limitations of these methodologies and provide examples of how they can be used to answer other policy-relevant questions. RESULTS: We argue that neuroscience techniques can provide more objective evidence of the impacts of policy measures, allow investigation where it is not possible to conduct behavioral manipulations, and facilitate a deeper understanding of the cognitive mechanisms underlying the impacts of tobacco control policies such as standardized packaging, health warnings, point-of-sale displays, and mass media campaigns. CONCLUSIONS: Rather than replacing more traditional methods of examining tobacco control measures, such as observational experiments, surveys, and questionnaires, neuroscience techniques can complement and extend these methods. IMPLICATIONS: Neuroscience techniques facilitate objective examination of the mechanisms underlying the impacts of tobacco control measures. These techniques can therefore complement and extend other methodologies typically used in this field, such as observational experiments, surveys, and questionnaires.

Background Fueled by rapid technological advances over the past decade, there is growing interest in the use of smartphones to aid in smoking cessation. Hundreds of applications have been developed for this purpose, but little is known about how these applications are accessed and used by smokers or what features smokers believe would be most useful. Purpose The present study sought to understand the prevalence of smartphone ownership and patterns of use among smokers as well as the perceived utility of various smartphone application features for smoking cessation that are currently in development or already available. Methods Daily cigarette smokers (n = 224) reported on smartphone ownership, their patterns of smartphone usage, and perceived utility of features. Features were ranked according to perceived utility and differences in both perceived utility and general smartphone use patterns were examined as a function of demographic and smoking-related variables. Results Most smokers (80.4%) own a smartphone, but experience with smoking cessation applications is extremely rare (6.1%). Ownership and patterns of usage differed as a function of demographic and smoking-related variables. Overall, gain-framed features were rated as most useful, while loss-framed and interpersonal features were rated as least useful. Conclusions Mobile health interventions have the potential to reach a large number of smokers but are currently underutilized. Additional effort is needed to ensure parity in treatment access. Gain-framed messages may be especially useful for engaging smokers, even if other features ultimately drive treatment effects. Implications This study describes patterns of smartphone usage among smokers and identifies the smartphone application features smokers believe would be most useful during a quit attempt. Findings indicate which subgroups of smokers are most likely to be reached with mobile health interventions and suggests that inclusion of specific features may be helpful for engaging smokers in the smoking cessation process.

Tobacco has a higher rate of dependence than other drugs of abuse. However, the psychopharmacological effects of nicotine are incongruent with the tenacity of tobacco addiction since nicotine does not produce robust euphoria in humans or self-administration in rodents. A potential explanation is that nicotine amplifies the salience of other stimuli that have some incentive value, which could influence the initiation and persistence of smoking. However, the neural mechanisms of this process are unknown. One way that nicotine may amplify the salience of other stimuli is by enhancing reward prediction errors. We hypothesized that nicotine would enhance the neural response to unexpected (relative to expected) rewards compared to placebo. Twenty-three nonsmokers underwent two fMRI scans, following nicotine (1 mg) or placebo administration, while performing an outcome expectation task. In the task, a pair of cues was associated with either a subsequent reward (the image of a $100 bill) or a nonreward (the image of a blurry rectangle). On 20% of trials, the cue was followed by an unexpected outcome. Although nicotine did not affect the magnitude of prediction errors relative to placebo, nicotine did increase BOLD activation in the anterior insula/inferior frontal gyrus and decrease activation in the caudate across all outcome types (including both rewards and nonrewards). The insula and caudate could play a role in the initial effects of nicotine in nonsmokers, and these changes in baseline may be the mechanism that underlies how nicotine amplifies the salience of nondrug stimuli.

Purpose Electronic cigarette (e-cigarette) use continues to rise among adolescents, but little is known regarding their risk perceptions of e-cigarette use. We aimed to describe the lifetime use and perceived risk of e-cigarette use in the context of other risk-taking behaviors among adolescents in North Carolina. Methods Data were derived from the 2015 North Carolina Youth Risk Behavior Survey, which was administered to 503 middle school and 444 high school students in the Chapel Hill-Carrboro public school district. Survey participants self-reported their sex; ethnicity; school grade; ever-use of cigarettes, e-cigarettes, alcohol, and other illicit substances; perceived risk of harm of these products; and perceived view of their parents' and friends' perceptions of these products. Logistic regression analyses were used to assess associations between student-reported characteristics, risk behaviors, perceived product risk, and ever-use of e-cigarettes. Results This study found that 4.6% of middle school students and 37.2% of high school students reported ever-use of e-cigarettes. E-cigarette use increased and perception of e-cigarette risk decreased with advancing grade. Ever-use of e-cigarettes surpassed ever-use of combustible cigarettes at all grades; 49.4% of e-cigarette users had never smoked cigarettes. The perception that friends view e-cigarette use as "wrong" correlated negatively with e-cigarette use (adjusted odds ratio = 0.43; 95% confidence interval, 0.19-0.97). Limitations Self-reported results from students in one school district have limited generalizability to larger groups. Conclusion E-cigarette use among adolescents in North Carolina correlates positively with perceived friends' views of e-cigarettes, and use correlates negatively with personal perception of the risk of e-cigarettes. Based on our survey results, education and public health intervention regarding e-cigarette use may be best targeted at youth prior to their transition to high school.

Rationale Research is needed on initial smoking abstinence and relapse risk. Objective This study aims to investigate the effects of different durations of initial abstinence on sensitivity to smokingrelated stimuli and response inhibition in the context of a larger battery of outcome measures. Methods Smokers were randomly assigned to receive payment contingent on smoking abstinence across all 15 study days (15C) or just the final 2 days (2C). Smoking status and subject ratings were assessed daily. Participants completed fMRI sessions at baseline and day 14 during which they completed craving ratings after exposure to smoking-related and neutral stimuli and performed a response inhibition task. On day 15, participants completed a smoking preference session involving 20 exclusive choices between smoking and money. Results The payment contingencies were effective in producing greater smoking abstinence in the 15C vs. 2C conditions. Ratings of withdrawal decreased, while ratings of ease and confidence in abstaining increased in the 15C vs. 2C conditionsacrossthe15-daystudy.15Cparticipantswerelesslikely to choose the smoking option in the preference session. 15C participants reported greater reductions in craving compared to the 2C participants in the presence of smoking-related and neutral stimuli (i.e., decreases in generalized craving), but no differences were noted in cue reactivity per se or in response inhibition. Conclusions Results systematically replicate prior observations that a period 2 weeks of initial abstinence decreases the relative reinforcing effects of smoking and improves other outcomes associated with relapse risk compared to the initial day or two of a cessation effort, and extends them by underscoring the importance of generalized rather than cueinduced craving in relation to relapse risk during the initial weeks of smoking cessation.

Advantageous decision-making is an adaptive trade-off between exploring alternatives and exploiting the most rewarding option. This trade-off may be related to maladaptive decision-making associated with nicotine dependence; however, explore/exploit behavior has not been previously investigated in the context of addiction. The explore/exploit trade-off is captured by the multi-armed bandit task, in which different arms of a slot machine are chosen to discover the relative payoffs. The goal of this study was to preliminarily investigate whether smokers differ from non-smokers in their degree of exploratory behavior. Smokers (n = 18) and non-smokers (n = 17) completed a six-armed bandit task as well as self-report measures of behavior and personality traits. Smokers were found to exhibit less exploratory behavior (i.e. made fewer switches between slot machine arms) than non-smokers within the first 300 trials of the bandit task. The overall proportion of exploratory choices negatively correlated with self-reported measures of delay aversion and nonplanning impulsivity. These preliminary results suggest that smokers make fewer initial exploratory choices on the bandit task. The bandit task is a promising measure that could provide valuable insights into how nicotine use and dependence is associated with explore/exploit decision-making.

Individuals with Attention Deficit Hyperactivity Disorder (ADHD) smoke cigarettes at rates higher than the general population and questions have been raised about how stimulant drugs – the frontline pharmacological treatment for ADHD – influence smoking risk and behavior in those with ADHD. In the present study adult regular smokers with (n=16) and without (n=17) ADHD participated in 3 experimental sessions in which they completed a Progressive Ratio (PR) task to measure the relative reinforcing effects of cigarette smoking and money following oral administration of placebo and 2 active doses of methylphenidate (10 mg and 40 mg). We also measured attention and inhibitory control via a Continuous Performance Test (CPT). Methylphenidate had no effect on smoking-reinforced responding, attention, or inhibitory control in either group. Attention and inhibitory control were associated with smoking-reinforced responding, but unsystematically and only in the non-ADHD group. Several design features, such as the value of the monetary response option, the PR schedule, and the potential effects of smoking on attention and inhibitory control, could have contributed to the negative findings and are discussed as such. Although inconsistent with some previous human laboratory studies of stimulant drugs and smoking, results are consistent with recent trials of stimulant drugs as adjuncts for smoking cessation in adult smokers with ADHD. In general, methylphenidate at mild and moderate doses did not influence the relative reinforcing effects of cigarette smoking in adults with and without ADHD.

Smoking withdrawal-induced disruption of affect and cognition is associated with dysregulated prefrontal brain function, although little is known regarding the neural foci of smoker–nonsmoker differences during affective cognition. Thus, the current study used functional magnetic resonance imaging (fMRI) to identify smoker–nonsmoker differences in affective cognition. Thirty-four healthy volunteers (17 smokers, 17 nonsmokers) underwent fMRI during an affective Stroop task (aST). The aST includes emotional cue-reactivity trials, and response selection trials that contain either neutral or negative emotional distractors. Smokers had less activation during negative cue-reactivity trials in regions subserving emotional awareness (i.e., posterior cingulate), inhibitory control (i.e., inferior frontal gyrus) and conflict resolution (i.e., anterior cingulate); during response-selection trials with negative emotional distractors, smokers had greater activation in a frontoparietal attentional network (i.e., middle frontal and supramarginal gyri). Exploratory analyses revealed that task accuracy was positively correlated with anterior cingulate cortex and inferior frontal gyrus response on fMRI. These findings suggests that chronic nicotine use may reduce inhibitory control and conflict resolution of emotional distraction, and result in recruiting additional attentional resources during emotional interference on cognition.

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 6 h 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.

The ventral and dorsal striatum are critical substrates of reward processing and motivation and have been repeatedly linked to addictive disorders, including nicotine dependence. However, little is known about how functional connectivity between these and other brain regions is modulated by smoking withdrawal and may contribute to relapse vulnerability. In the present study, 37 smokers completed resting state fMRI scans during both satiated and 24-h abstinent conditions, prior to engaging in a 3-week quit attempt supported by contingency management. We examined the effects of abstinence condition and smoking outcome (lapse vs non-lapse) on whole-brain connectivity with ventral and dorsal striatum seed regions. Results indicated a significant condition by lapse outcome interaction for both right and left ventral striatum seeds. Robust abstinence-induced increases in connectivity with bilateral ventral striatum were observed across a network of regions implicated in addictive disorders, including insula, superior temporal gyrus, and anterior/mid-cingulate cortex among non-lapsers; the opposite pattern was observed for those who later lapsed. For dorsal striatum seeds, 24-h abstinence decreased connectivity across both groups with several regions, including medial prefrontal cortex, posterior cingulate cortex, hippocampus, and supplemental motor area. These findings suggest that modulation of striatal connectivity with the cingulo-insular network during early withdrawal may be associated with smoking cessation outcomes.

Background Attention-deficit/hyperactivity disorder (ADHD) is a risk factor for problematic cannabis use. However, clinical and anecdotal evidence suggest an increasingly popular perception that cannabis is therapeutic for ADHD, including via online resources. Given that the Internet is increasingly utilized as a source of healthcare information and may influence perceptions, we conducted a qualitative analysis of online forum discussions, also referred to as threads, on the effects of cannabis on ADHD to systematically characterize the content patients and caregivers may encounter about ADHD and cannabis. Methods A total of 268 separate forum threads were identified. Twenty percent (20%) were randomly selected, which yielded 55 separate forum threads (mean number of individual posts per forum thread = 17.53) scored by three raters (Cohen’s kappa = 0.74). A final sample of 401 posts in these forum threads received at least one endorsement on predetermined topics following qualitative coding procedures. Results Twenty-five (25%) percent of individual posts indicated that cannabis is therapeutic for ADHD, as opposed to 8% that it is harmful, 5% that it is both therapeutic and harmful, and 2% that it has no effect on ADHD. This pattern was generally consistent when the year of each post was considered. The greater endorsement of therapeutic versus harmful effects of cannabis did not generalize to mood, other (non-ADHD) psychiatric conditions, or overall domains of daily life. Additional themes emerged (e.g., cannabis being considered sanctioned by healthcare providers). Conclusions Despite that there are no clinical recommendations or systematic research supporting the beneficial effects of cannabis use for ADHD, online discussions indicate that cannabis is considered therapeutic for ADHD—this is the first study to identify such a trend. This type of online information could shape ADHD patient and caregiver perceptions, and influence cannabis use and clinical care.

Although functional brain imaging has established that individuals with unipolar major depressive disorder (MDD) are characterized by frontostriatal dysfunction during reward processing, no research to date has examined the chronometry of neural responses to rewards in euthymic individuals with a history of MDD.A monetary incentive delay task was used during fMRI scanning to assess neural responses in frontostriatal reward regions during reward anticipation and outcomes in 19 participants with remitted major depressive disorder (rMDD) and in 19 matched control participants.During the anticipation phase of the task, the rMDD group was characterized by relatively greater activation in bilateral anterior cingulate gyrus, in right midfrontal gyrus, and in the right cerebellum. During the outcome phase of the task, the rMDD group was characterized by relatively decreased activation in bilateral orbital frontal cortex, right frontal pole, left insular cortex, and left thalamus. Exploratory analyses indicated that activation within a right frontal pole cluster that differentiated groups during reward anticipation predicted the number of lifetime depressive episodes within the rMDD group.Replication with larger samples is needed.Results suggest a double dissociation between reward network reactivity and temporal phase of the reward response in rMDD, such that rMDD is generally characterized by reward network hyperactivation during reward anticipation and reward network hypoactivation during reward outcomes. More broadly, these data suggest that aberrant frontostriatal response to rewards may potentially represent a trait marker for MDD, though future research is needed to evaluate the prospective utility of this functional neural endophenotype as a marker of MDD risk.

INTRODUCTION Smoking prevalence among individuals with posttraumatic stress disorder (PTSD) is elevated relative to non-PTSD smokers, and there is evidence to suggest that affect regulation may be a motivation for smoking among those with this disorder. Previous studies have also indicated that (a) PTSD is frequently comorbid with attention-deficit/hyperactivity disorder (ADHD), (b) individuals with ADHD smoke at significantly higher rates than the general population, (c) subclinical ADHD symptoms are a risk factor for smoking, and (d) affect regulation is a motivation for smoking in ADHD. The goal of this study was to assess the degree to which ADHD symptoms were uniquely associated with smoking-related affective functioning (SRAF) variables above and beyond the variance already explained by PTSD symptoms. METHODS Smokers with (n = 55) and without PTSD (n = 68) completed measures assessing PTSD symptoms, ADHD symptoms, and SRAF. RESULTS The PTSD group endorsed significantly more severe levels of DSM-IV inattentive and hyperactive-impulsive ADHD symptoms. A series of hierarchical regressions among the entire sample indicated that, after accounting for PTSD symptoms, ADHD symptoms were associated with lower positive affect, higher negative affect, higher emotion dysregulation, higher anxiety sensitivity, and higher urges to smoke to increase positive affect. CONCLUSIONS Taken together, these findings suggest that ADHD symptoms may increase affective dysregulation difficulties already faced by smokers, particularly those with PTSD, which may, in turn, confer increased risk for smoking relapse in those with higher levels of symptomatology of both disorders.

Background Previous functional magnetic resonance imaging studies have shown strong correlations between cue-elicited craving for cigarettes and activation of the superior frontal gyrus (SFG). Repetitive transcranial magnetic stimulation (rTMS) offers a noninvasive means to reversibly affect brain cortical activity, which can be applied to testing hypotheses about the causal role of SFG in modulating craving. Methods Fifteen volunteer smokers were recruited to investigate the effects of rTMS on subjective responses to smoking versus neutral cues and to controlled presentations of cigarette smoke. On different days, participants were exposed to three conditions: 1) high-frequency (10 Hz) rTMS directed at the SFG; 2) low-frequency (1 Hz) rTMS directed at the SFG; and 3) low-frequency (1 Hz) rTMS directed at the motor cortex (control condition). Results Craving ratings in response to smoking versus neutral cues were differentially affected by the 10-Hz versus 1-Hz SFG condition. Craving after smoking cue presentations was elevated in the 10-Hz SFG condition, whereas craving after neutral cue presentations was reduced. Upon smoking in the 10-Hz SFG condition, ratings of immediate craving reduction as well as the intensity of interoceptive airway sensations were also attenuated. Conclusions These results support the view that the SFG plays a role in modulating craving reactivity; moreover, the results suggest that the SFG plays a role in both excitatory and inhibitory influences on craving, consistent with prior research demonstrating the role of the prefrontal cortex in the elicitation as well as inhibition of drug-seeking behaviors.

Attention-deficit hyperactivity disorder (ADHD) is associated with multiple cognition-related phenotypic features in both children and adults. This review aims to clarify the role of cognition in ADHD and how prevailing treatments, which are often highly effective at reducing the clinical symptoms of the disorder, fare in modulating ADHD-related cognitive processes. First, we consider how the broad construct of cognition can be conceptualized in the context of ADHD. Second, we review the available evidence for how a range of both pharmacological and non-pharmacological interventions have fared with respect to enhancing cognition in individuals affected by this pervasive disorder. Findings from the literature suggest that the effects across a broad range of pharmacological and non-pharmacological interventions on the characteristic symptoms of ADHD can be distinguished from their effects on cognitive impairments. As such the direct clinical relevance of cognition enhancing effects of different interventions is somewhat limited. Recommendations for future research are discussed, including the identification of cognition-related end ophenotypes, the refinement of the ADHD clinical phenotype, and studying the difference between acute and chronic treatment regimens.

Acute nicotine abstinence is associated with disruption of executive function and reward processes; however, the neurobiological basis of these effects has not been fully elucidated.The effects of nicotine abstinence on brain function during reward-based probabilistic decision making were preliminarily investigated by scanning adult smokers (n = 13) following 24 h of smoking abstinence and in a smoking-satiated condition. During fMRI scanning, participants completed the wheel of fortune task (Ernst et al. in Neuropsychologia 42:1585-1597, 2004), a decision-making task with probabilistic monetary outcomes. Brain activation was modeled during selection of options, anticipation of outcomes, and outcome feedback.During choice selection, reaction times were slower, and there was greater neural activation in the postcentral gyrus, insula, and frontal and parietal cortices in the abstinent condition compared to the satiated condition. During reward anticipation, greater activation was observed in the frontal pole, insula, and paracingulate cortex in the abstinent condition compared to the satiated condition. Greater activation was also shown in the precentral gyrus and putamen in the satiated condition compared to the abstinent condition. During the outcome phase, rewards (compared to no rewards) resulted in significant activation in the paracingulate cortex in the satiated condition compared to the abstinent condition.The results of this preliminary study suggest that smoking withdrawal results in greater recruitment of insular, frontal, and parietal cortical areas during probabilistic decision making.

Individuals with attention-deficit/hyperactivity disorder (ADHD) smoke cigarettes at higher rates and have greater difficulty quitting than their non-diagnosed peers. This study examined differences between smokers with and without ADHD on a range of smoking-related variables. Twenty-two subjects with ADHD and 22 controls completed self-report measures of withdrawal symptoms, smoking motivation, sensory experience of smoking, and positive and negative affect. Compared to control smokers, smokers with ADHD reported greater craving and negative affect; perceived smoking as providing greater enhancement of concentration and alertness, as more calming, and as providing a greater decrease in irritability; found cigarette puffs to be more enjoyable and satisfying; and rated smoking as providing greater positive and negative reinforcement and greater cognitive enhancement. Women with ADHD reported the greatest effects of smoking on improving concentration and reducing irritability. Findings support the hypothesi...

Exaggerated startle response is a prominent feature of posttraumatic stress disorder (PTSD) although results examining differences in the acoustic startle response (ASR) between those with and without PTSD are mixed. One variable that may affect ASR among persons with PTSD is smoking. Individuals with PTSD are more likely to smoke and have greater difficulty quitting smoking. While smokers with PTSD report that smoking provides significant relief of negative affect and PTSD symptoms, the effects of smoking or nicotine deprivation on startle reactivity among smokers with PTSD are unknown.The purposes of the current study were to (1) examine baseline acoustic startle response (ASR) in smokers with and without PTSD under conditions of overnight abstinence, (2) evaluate the effect of smoking on ASR, and (3) evaluate the contextual effects of trauma versus neutral script presentations.ASR was measured among 48 smokers with and without PTSD in the context of a 2 (group: PTSD vs. non-PTSD) x 2 (context: trauma vs. neutral) x 3 (smoking condition: usual brand cigarette vs. denicotinized cigarette vs. no smoking) design.Effects of modest size indicated that (1) PTSD participants demonstrated higher ASR (2) compared to non-PTSD participants, PTSD participants reported greater negative affect following a trauma-related script, and (3) following a trauma-related script and smoking a usual brand cigarette, PTSD participants demonstrated higher ASR.Although many smokers with PTSD report that smoking reduces PTSD symptoms, results suggest that smoking may actually potentiate or maintain an exaggerated startle response.

Smoking withdrawal is associated with significant deficits in the ability to initiate and maintain attention for extended periods of time (i.e. sustained attention; SA). However, the effects of smoking abstinence on the temporal dynamics of neurocognition during SA have not been evaluated. Twenty adult smokers underwent functional magnetic resonance imaging scans following smoking as usual and after 24-hours abstinence. During scanning they completed a SA task with two levels of task difficulty, designed to measure both sustained (i.e. over the duration of the task) and transient (i.e. event-related) activation. Smoking abstinence significantly decreased task accuracy regardless of task difficulty. Compared to smoking as usual, abstinence resulted in decreased sustained activation in right inferior and middle frontal gyri but increased transient activation across dispersed cortical areas including precuneus and right superior frontal gyrus. Greater task difficulty was associated with even greater transient activation during abstinence in mostly right hemisphere regions including right inferior frontal gyrus. These findings suggest smoking withdrawal shifts the temporal and spatial dynamics of neurocognition from sustained, right prefrontal activation reflecting proactive cognitive control (Braver, Gray & Burgess 2009) to more dispersed and transient activation reflecting reactive control.

Smokers exhibit decrements in inhibitory control (IC) during withdrawal. The objective of this study was to investigate the neural basis of these effects in critical substrates of IC--right inferior frontal cortex (rIFC) and presupplementary motor area (pre-SMA). Smokers were scanned following smoking as usual and after 24-h smoking abstinence. During scanning they completed a Go/No-Go task that required inhibiting responses to infrequent STOP trials. Event-related brain activation in response to successfully inhibited STOP trials was evaluated in two regions of interest: rIFC (10 mm sphere, x=40, y=30, z=26) and pre-SMA (10 mm sphere, x=2, y=18, z=40). Smoking abstinence robustly increased errors of commission on STOP trials (37.1 vs 24.8% in the satiated condition, p

Compared to nonsmokers, smokers exhibit a number of potentially important differences in regional brain structure including reduced gray matter (GM) volume and/or density in areas including frontal and cingulate cortices, thalamus, and insula. However, associations between brain structure and smoking cessation treatment outcomes have not been reported.In the present analysis we sought to identify associations between regional GM volume--as measured by voxel-based morphometry (VBM)--and a smoking cessation treatment outcome (point prevalence abstinence at 4 weeks).Adult smokers underwent high-resolution anatomical MRI scanning prior to an open label smoking cessation treatment trial. VBM was conducted in SPM5 using the DARTEL algorithm and relapser vs. quitter groups were compared using independent sample t tests (p0.001, uncorrected). Analyses controlled for potentially confounding factors including years smoked, cigarettes per day, total intracranial volume (TIV), and sex.Of 18 smokers, 8 achieved a 4-week point prevalence abstinence, confirmed by CO level (or=8 ppm). After controlling for all covariates, compared to relapsers, quitters had significantly higher GM volume in the left putamen and right occipital lobe, while also significantly lower GM volume in bilateral hippocampus and right cuneus.These preliminary results suggest that maintaining smoking abstinence is associated with higher pre-quit brain volume in regions that subserve habit learning and visual processing, and lower brain volume in regions that subserve long-term memory processes and visual information processing. Future, large-scale studies can determine whether brain structure variables can serve as clinically useful predictors of smoking cessation treatment outcome.

Dependent smokers exhibit deficits in attentional and memory processes when smoking abstinent as compared to when satiated. While nicotine replacement therapy improves attention during abstinence, it is unclear whether this is due to the alleviation of withdrawal-related deficits or inherent beneficial effects of nicotine. The primary aim of these studies was to test whether nicotine exerts a beneficial effect on novelty detection and whether such effects occur in nonsmokers as well as habitual smokers. In two parallel, double-blind, placebo-controlled studies, 24 smokers (study 1) and 24 nonsmokers (study 2) were tested in two counterbalanced sessions: once while wearing a nicotine patch (smokers = 14 mg; nonsmokers = 7 mg) and once while wearing a placebo patch. On each day, participants performed three content-specific oddball tasks (perceptual, semantic, and emotional) that required them to press a button whenever they saw a novel target (20% of stimuli) embedded in a stream of common nontarget stimuli (80% of stimuli). Recognition memory for targets was subsequently tested. Reports of mood, smoking withdrawal, patch side effects, and blind success were collected in each session. Among smokers, compared to placebo, nicotine decreased target reaction time during all oddball tasks. Among nonsmokers, nicotine increased target detection accuracy and subsequent memory recognition. Nicotine’s enhancement on each respective measure was not task-content specific in either sample. These data suggest that acute nicotine administration may exert direct beneficial effects on novelty detection and subsequent memory recognition in both smokers and nonsmokers. Moreover, these effects are not content-specific.

To assess the effects of postnatal parental smoking on subsequent parent and teacher ratings of DSM-IV attention deficit hyperactivity disorder (ADHD) symptoms and oppositional behaviors in children diagnosed with ADHD and their siblings. Children between 5 and 12 years of age with ADHD and their siblings were included. DSM-IV ADHD symptom subscales (Inattentive and hyperactive-impulsive), and oppositionality subscale scores from Conners’ Rating Scales were predicted on the basis of parental smoking status in the first 7 years after birth using Generalized Estimating Equations controlling for a range of relevant covariates. Postnatal parental smoking was associated with both parent and teacher ratings of ADHD symptoms and oppositional behavior. After controlling for a number of covariates, several of these relationships were still significant. The risk of maternal smoking for the development of ADHD symptoms does not end during pregnancy. Research on the mechanisms underlying the observed associations is needed.

Modern neuroimaging techniques offer the opportunity to non-invasively study neuroanatomical and neurofunctional correlates of nicotine dependence and its treatment. In the present review, the most widely used neuroimaging techniques—magnetic resonance imaging (MRI), positron emission tomography (PET) and functional MRI (fMRI)—are briefly described and their strengths and limitations discussed. The use of these techniques has resulted in new insights into the neuropharmacology of tobacco addiction. Studies comparing smokers and nonsmokers have shown that smokers have less grey matter density in frontal brain regions and greater concentrations of nicotinic receptors. Research on the effects of smoking a cigarette confirms that smoking leads to the release of dopamine in brain reward areas and to nicotinic receptor binding. Studies of smoking abstinence have identified functional brain correlates of increased reactivity to smoking-related cues, and worsening of concentration. To date, neuroimaging studies of nicotine dependence among individuals with mental illness have focused almost exclusively on schizophrenia. A conceptual/methodological framework for studying dual diagnosis using neuroimaging measures is provided with the aim of spurring additional research in this area.

Depression and Genetic variation in serotonin and monoamine transmission have both been associated with body mass index (BMI), but their interaction effects are not well understood. We examined the interaction between depressive symptoms and functional polymorphisms of serotonin transporter (SLC6A4) and monoamine oxidase A (MAOA) on categories of BMI. Participants were from the National Longitudinal Study of Adolescent Health. Multiple logistic regression was used to investigate interactions between candidate genes and depression on risk of obesity (BMIor = 30) or overweight + obese combined (BMIor = 25). Males with an MAOA active allele with high depressive symptoms were at decreased risk of obesity (OR 0.22; 95% CI 0.06-0.78) and overweight + obesity (OR 0.48; 95% CI 0.26-0.89). No similar effect was observed among females. These findings highlight that the obesity-depression relationship may vary as a function of gender and genetic polymorphism, and suggest the need for further study.

Smoking abstinence differentially affects cognitive functioning in smokers with ADHD, compared to non-ADHD smokers. Alternative approaches for analyzing reaction time data from these tasks may further elucidate important group differences. Adults smoking ≥15 cigarettes with (n = 12) or without (n = 14) a diagnosis of ADHD completed a continuous performance task (CPT) during two sessions under two separate laboratory conditions—a ‘Satiated’ condition wherein participants smoked up to and during the session; and an ‘Abstinent’ condition, in which participants were abstinent overnight and during the session. Reaction time (RT) distributions from the CPT were modeled to fit an ex-Gaussian distribution. The indicator of central tendency for RT from the normal component of the RT distribution (mu) showed a main effect of Group (ADHD Satiated), Group × Session interaction (ADHD increased significantly under Abstinent condition compared to Control), and a trend toward a main effect of Group (ADHD > Control). Alternative approaches to analyzing RT data provide a more detailed description of the effects of smoking abstinence in ADHD and non-ADHD smokers and results differ from analyses using more traditional approaches. These findings have implications for understanding the neuropsychopharmacology of nicotine and nicotine withdrawal.

Exposure to smoking-related cues can trigger relapse in smokers attempting to maintain abstinence.In 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).Eighteen 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.Following 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).The 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.

Attention-deficit/hyperactivity disorder (ADHD) symptoms are associated with an increased risk of smoking, and genetic studies have identified similar candidate genes associated with both ADHD and smoking phenotypes. This paper addresses the question of whether ADHD symptoms interact with candidate gene variation to predict smoking risk. Participants were a subsample of individuals from the National Longitudinal Study of Adolescent Health (Add Health), a nationally representative sample of adolescents followed from 1995 to 2002. The sample analyzed included a subset from Add Health of 1,900 unrelated individuals with genotype data. Multiple logistic regression was used to examine relationships between self-reported ADHD symptoms, genotype, and lifetime history of regular smoking. Polymorphisms in the DRD2 gene and, among females, the MAOA gene interacted with retrospective reports of ADHD symptoms in contributing to risk for smoking. Trends were observed for interactions between the DRD4 gene and, among males, the MAOA gene and ADHD symptoms to predict smoking risk. No main effect for any of these polymorphisms was observed. We observed neither main effects nor interactions with CYP2A6, DAT, and SLC6A4 genes. These findings suggest that genotypes associated with catecholamine neurotransmission interact with ADHD symptoms to contribute to smoking risk.

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).

The study investigated the effects of smoking a nicotinized or denicotinized cigarette on craving, affect and posttraumatic stress disorder (PTSD) symptoms while recalling neutral, stressful and traumatic events in smokers with and without PTSD. Smokers completed laboratory sessions during which they were presented with audiotapes of personalized scripts followed by smoking a cigarette. The effect of the script and cigarette conditions on dependent variables was evaluated. There was a main effect of script type across groups for smoking craving, negative affect and PTSD symptoms, with increased symptoms in trauma and stressful conditions. Responses were significantly higher in PTSD smokers. Smoking either cigarette type resulted in decreased craving, negative affect and PTSD symptoms in both groups. A second script presentation following smoking elicited similar responses, suggesting the ameliorative effect of having smoked a cigarette was short-lived. These results support that context and non-pharmacologic effects of smoking are important variables in smoking craving and mood, particularly in smokers with PTSD.

Trait impulsivity and response inhibition have been shown to be related to smoking behavior. One measure of response inhibition - antisaccade performance, or the ability to inhibit looking at a novel stimulus - has been shown to be worsened by smoking abstinence, improved by nicotine administration and predictive of smoking cessation outcomes. However, relations between antisaccade performance and measures of trait impulsivity have not been extensively evaluated in smokers. In the present study, twelve dependent smokers (n=12) completed an eye tracking task following smoking as usual and overnight abstinence; and they completed baseline measures of trait impulsivity, smoking history and provided biological samples. As expected, overnight abstinence significantly increased antisaccade errors (p

In this chapter, we review the last decade of research on the effects of smoking abstinence on various forms of neurocognition, including executive function (working memory, sustained attention, response inhibition), reward processing, and cue-reactivity. In our review we identify smoking abstinence-induced deficits in executive function mediated by effects on frontal circuitry, which in turn is known to be affected by modulation of cholinergic, dopaminergic, and other neurotransmitter systems. We also review evidence that smoking abstinence blunts reactivity to non-drug reinforcers—a finding that is consistent with results in the animal literature. Finally, our review of cue-reactivity indicates that smoking abstinence does not appear to amplify cue-provoked craving, although it may increase attentional bias to smoking-related cues. Inconsistencies across findings and potential contributing factors are discussed. In addition, we review the literature on the effects of nicotine and non-nicotine factors in neurocognition. Finally, we provide a multi-factor model and an agenda for future research on the effects of smoking abstinence on neurocognition. The model includes four distinct yet interacting factors, including: Negative Reinforcement, Drug-Reward Bias, Goal and Skill Interference, and Non-Cognitive Factors. Additional research is needed to further evaluate the scope and time-course of abstinence-induced changes in neurocognition, the mechanisms that underlie these changes and the specific role of these processes in drug reinforcement, lapse, and relapse.

Current evidence indicates that, although African Americans (AA) are more likely to attempt to quit smoking than Caucasians (CC) in any given year, success rates are lower for AA. However, factors contributing to these differences are not well known. In order to explore potential factors, this study assessed differences in attention to smoking cues between ethnic groups. Participants underwent morning functional magnetic resonance imaging scanning while viewing images of AA models and CC models who were either smoking (smoking cues) or engaging in everyday activities (neutral cues), interspersed with a fixation baseline period. The study was conducted at the Hoglund Brain Imaging Center of the University of Kansas Medical Center in Kansas City, KS. We studied 17 smokers (eight AA, nine CC) after 12-hour abstinence and 17 non-smokers (eight AA, nine CC) matched by age, gender, years of education, and handedness. The AA and CC smoking groups were also matched for number of cigarettes smoked per day. All results are P < 0.01, corrected for whole brain. There was a strong ethnicity by condition interaction among smokers in several a priori regions of interest. AA smokers showed a greater increase in response to smoking (versus neutral cues) than CC smokers in the medial prefrontal cortex, right lateral orbitofrontal cortex, and bilateral ventrolateral prefrontal cortex. In smoking versus baseline contrasts, additional areas of greater activation were found in AA, including the right amygdala and left caudate nucleus. No significant differences in cue-elicited brain activation were found between AA and CC non-smokers. These preliminary findings demonstrate variation in brain activation in response to smoking cues between AA and CC smokers in structures known to be associated with nicotine addiction. Differences in neural response may reflect fundamental differences in attention to smoking cues, which may in turn contribute to differences in effectiveness of nicotine dependence treatments among ethnic populations.

Drug cues have been shown to activate brain regions involved in attention, motivation, and reward in addicted users. However, as studies have typically measured responses in only one state (ie drug abstinence), it is unclear whether observed activations represent amplification by abstinence or stable responses. Thus, the present study was designed to evaluate the stability of event-related responses to visual drug cues in dependent smokers (n = 13) using event-related functional magnetic resonance imaging measures. Imaging was conducted following smoking as usual and following overnight abstinence, and self-reported craving measures were obtained before, during, and after scanning. Analysis of hemodynamic response (HDR) amplitudes in each of 13 regions of interest revealed larger responses to smoking compared to control cues in ventral anterior cingulate gyrus (vACG) and superior frontal gyrus. Responses to smoking cues in these and all other regions revealed no effects of abstinence/satiety, thus supporting the notion that cue-elicited brain responses are relatively stable. However, while the abstinence manipulation did not alter group-level responses to smoking cues, at the individual level, abstinence-induced changes in craving (abstinence minus satiety) were positively correlated with changes in HDR amplitude to smoking cues in frontal regions including left inferior frontal gyrus, left vACG, and bilateral middle frontal gyrus. These results suggest that brain responses to smoking cues, while relatively stable at the group level following short-term abstinence, may be modulated by individual differences in craving in response to abstinence—particularly in regions subserving attention and motivation.

Given that nicotine reduces negative affect, one would expect nicotine to have different effects on brain responses to emotionally negative stimuli than it does on responses to emotionally neutral or positive stimuli. However, no studies have assessed this possibility. The present study assessed the effects of nicotine patch versus placebo patch on brain event-related potential (ERP) responses to emotion-inducing negative, positive, and neutral color pictures in 16 smokers in a double-blind, counterbalanced, within-subjects design. The study included four experimental sessions. After overnight smoking deprivation (12 hr or more), active nicotine patches were applied to participants during one of the first two sessions and during one of the last two sessions. Placebo patches were applied during the other two sessions. Nicotine reduced frontal ERP processing voltage negativity (from 144-488 ms poststimulus onset) evoked by viewing emotionally negative pictures to a greater extent than it did when emotionally neutral pictures were viewed, whereas it had no effect on processing negativity evoked by positive pictures. Nicotine also enhanced P390 amplitudes evoked by emotionally negative pictures more than it did when emotionally neutral and positive pictures were viewed. Across picture types, nicotine (relative to placebo) reduced N300 amplitude (more at anterior and dorsal sites) and increased P390 amplitude. Overall, nicotine influenced ERPs to emotionally neutral and positive pictures less than it did to negative pictures.

Changes in physiology and attentional performance associated with smoking abstinence were characterized in 67 female smokers during low-stress and high-stress conditions. Abstinence was associated with decreases in cognitive performance, heart rate, and electroencephalographic (EEG) activation but with no change in serum estradiol or progesterone. Effects of quitting showed no tendency to resolve across the 31 days of abstinence. EEG deactivation and heart rate slowing were greater during a math task (high stress) than during relaxation (low stress). Individuals high in trait depression or nicotine dependence or with at least one dopamine D(2) receptor A1 allele experienced greater EEG deactivation following abstinence, especially in the right hemisphere during the stressful task. Thus, findings support the situation x trait adaptive response model of abstinence effects and emphasize the value of multiple dependent measures when characterizing abstinence responses.

It has been proposed that nicotine may enhance performance on tasks requiring primarily left hemisphere (LH) resources while impairing right hemisphere (RH)-based performance. However, this hypothesis has not been directly tested using a lateralized cognitive task. The effects of transdermal nicotine administration on lateralized consonant identification and memory interference were examined in dependent smokers and never-smokers. In a double-blind placebo-controlled design, smokers (n = 24) and never-smokers (n = 24) were assigned to receive a nicotine or placebo patch. Subjects completed a lateralized letter identification task that required them to identify strings of three consonants presented in the left or right visual field while keeping a word in memory. A distinct right-visual-field (RVF) advantage was observed for consonant identification, but this effect was unaltered by nicotine or smoking status. However, nicotine decreased word memory errors on trials where consonants were presented in the RVF and increased errors on LVF trials. Nicotine may enhance LH-based cognitive performance by increasing LH cognitive resources or by reducing the influence of RVF distracting stimuli. These findings are consistent with a model of the lateralized effects of nicotine on cognitive performance. Copyright © 2003 John Wiley & Sons, Ltd.