Brain Responses to Cigarette-Related and Emotional Images in Smokers During Smoking Cessation: No Effect of Varenicline or Bupropion on the Late Positive Potential.

Introduction: Varenicline and bupropion are two effective smoking cessation pharmacotherapies. Researchers have hypothesized that they might be effective, in part, because they reduce cue reactivity and cue-induced cravings. Here, we used event-related potentials (ERPs) to directly measure brain responses to cigarette-related and other motivationally relevant images during a pharmacologically aided quit attempt. Methods: Smokers involved in a 12-week placebo-controlled double-blind clinical trial of smoking cessation medications (varenicline, bupropion, placebo) took part in the study. We assessed participants at two time points: 24 h (n = 140) and 4 weeks (n = 176) after the quit date. At both sessions, we measured the amplitude of the late positive potential (LPP), an ERP component reliably associated with motivational relevance, and self-reported tonic craving using the brief version of the Questionnaire of Smoking Urges (QSU-Brief). Results: At both sessions, emotional and cigarette-related images evoked significantly larger LPPs than neutral images. Neither drug type nor smoking abstinence altered this effect at either session. At both sessions, varenicline and bupropion significantly reduced self-reported tonic craving relative to the placebo condition. Conclusions: While both varenicline and bupropion reduced self-reported tonic craving, neither medication altered the amplitude of the LPP to cigarette-related or emotional pictures in smokers attempting to quit. These medications may influence abstinence by means other than by reducing neuroaffective responses to cigarette-related cues. Smokers should be prepared for the likelihood that even after several weeks of successful abstinence, once treatment ends, cigarette-related cues may remain motivationally relevant and trigger cravings that might lead to relapse. Implications: Bupropion and varenicline do not alter electrophysiological responses, as measured by the LPP, to cigarette-related and emotional images. These findings help explain why cigarette-related cues can trigger relapse when smoking cessation medication treatments end.

Beyond Cue Reactivity: Non-Drug-Related Motivationally Relevant Stimuli Are Necessary to Understand Reactivity to Drug-Related Cues.

Neurobiological models of addiction posit that drug use can alter reward processes in two ways: (1) by increasing the motivational relevance of drugs and drug-related cues and (2) by reducing the motivational relevance of non-drug-related rewards. Here, we discuss the results from a series of neuroimaging studies in which we assessed the extent to which these hypotheses apply to nicotine dependence. In these studies, we recorded smokers' and nonsmokers' brain responses to a wide array of motivationally relevant visual stimuli that included pleasant, unpleasant, cigarette-related, and neutral images. Based on these findings, we highlight the flaws of the traditional cue reactivity paradigm and we conclude that responses to non-drug-related motivationally relevant stimuli should be used to appropriately gauge the motivational relevance of cigarette-related cues and to identify smokers attributing higher motivational relevance to drug-related cues than to non-drug-related rewards. Identifying these individuals is clinically relevant as they achieve lower rates of long-term smoking abstinence when attempting to quit. Finally, we show how this approach may be extended beyond nicotine dependence to inform theoretical and clinical research in the study of obesity. Implications: The cue reactivity paradigm (ie, comparing responses evoked by drug-related cues to those evoked by neutral cues) cannot provide conclusive information about the motivational relevance of drug-related cues. Responses to non-drug-related motivationally relevant stimuli should be used to appropriately gauge the level of motivational relevance that substance-dependent individuals attribute to drug-related cues.

Prequit fMRI responses to pleasant cues and cigarette-related cues predict smoking cessation outcome.

INTRODUCTION: The reasons that some smokers find it harder to quit than others are unclear. Understanding how individual differences predict smoking cessation outcomes may allow the development of more successful personalized treatments for nicotine dependence. Theoretical models suggest that drug users might be characterized by increased sensitivity to drug cues and by reduced sensitivity to nondrug-related natural rewards. We hypothesized that baseline differences in brain sensitivity to natural rewards and cigarette-related cues would predict the outcome of a smoking cessation attempt. METHODS: Using functional magnetic resonance imaging, we recorded prequit brain responses to neutral, emotional (pleasant and unpleasant), and cigarette-related cues from 55 smokers interested in quitting. We then assessed smoking abstinence, mood, and nicotine withdrawal symptoms during the course of a smoking cessation attempt. RESULTS: Using cluster analysis, we identified 2 groups of smokers who differed in their baseline responses to pleasant cues and cigarette-related cues in the posterior visual association areas, the dorsal striatum, and the medial and dorsolateral prefrontal cortex. Smokers who showed lower prequit levels of brain reactivity to pleasant stimuli than to cigarette-related cues were less likely to be abstinent 6 months after their quit attempt, and they had higher levels of negative affect during the course of the quit attempt. CONCLUSIONS: Smokers with blunted brain responses to pleasant stimuli, relative to cigarette-related stimuli, had more difficulty quitting smoking. For these individuals, the lack of alternative forms of reinforcement when nicotine deprived might be an important factor underlying relapse. Normalizing these pathological neuroadaptations may help them achieve abstinence.

Using eye tracking to evaluate the impact of smartphone-delivered attentional bias modification training for smokers.

Attentional bias modification (ABM) has been proposed to treat tobacco use disorder by reducing attentional bias (AB) to smoking-related cues. We sought to determine the extent to which AB to smoking cues, as measured by eye-tracking technology, was sensitive to multisession ABM among treatment-seeking adult smokers. The participants (N = 203; 74 women) completed 13 days of daily ABM or sham training using a smartphone, followed by 8 weeks of nicotine replacement therapy and cessation counseling. ABM and sham training were administered using the modified dot-probe task (i.e., neutral cues probed 100% of the time) and the unmodified dot-probe task (i.e., cue types probed equally), respectively. Eye gaze dwell time proportions to paired presentations of smoking and neutral cues were measured at baseline, 1 day post-ABM training, and 8 weeks post-ABM training. At baseline, younger, more dependent smokers and those with higher smoking satisfaction scores looked longer at smoking cues than neutral ones. ABM training resulted in greater gaze preference for the smoking cues than sham training at 1 day posttraining. Gaze preference for smoking cues was positively associated with AB to smoking cues as measured by reaction time during the laboratory dot-probe assessment. At 8 weeks posttraining, gaze preference was not associated with any of the smoking outcome measures. These findings suggest that multisession ABM training resulted in changes in AB by increasing time spent looking at neutral compared with smoking cues in the short term. However, this effect was not sustained and was not associated with smoking behavior outcomes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Alpha oscillations in response to affective and cigarette-related stimuli in smokers.

INTRODUCTION: The presence of cigarette-related cues has been associated with smoking relapse. These cues are believed to activate brain mechanisms underlying emotion, attention, and memory. Electroencephalography (EEG) alpha desynchronization (i.e., reduction in alpha power) has been suggested to index the engagement of these mechanisms. Analyzing EEG alpha desynchronization in response to affective and smoking cues might improve our understanding of how smokers process these cues, and the potential impact of this processing on relapse. METHODS: Before the start of a medication-assisted cessation attempt, we recorded EEG from 179 smokers during the presentation of neutral, pleasant, unpleasant, and cigarette-related pictures. Wavelet analysis was used to extract EEG alpha oscillations (8-12 Hz) in response to these pictures. Alpha oscillations were analyzed as a function of picture valence and arousal dimensions. RESULTS: Emotional and cigarette-related stimuli induced a higher level of alpha desynchronization (i.e., less power in the alpha frequency band) than neutral stimuli. In addition, the level of alpha desynchronization induced by cigarette-related stimuli was similar to that induced by highly arousing stimuli (i.e., erotica and mutilations). CONCLUSIONS: These results suggest that, for smokers, cigarette-related cues are motivationally significant stimuli that may engage emotional, attentional, and memory-related neural mechanisms at a level comparable to that seen in response to highly arousing stimuli. This finding suggests that activation of emotional, attentional, and memory-related brain mechanisms may be an important contributor to cue-induced smoking relapse.

Neural substrates of smoking cue reactivity: a meta-analysis of fMRI studies.

Reactivity to smoking-related cues may be an important factor that precipitates relapse in smokers who are trying to quit. The neurobiology of smoking cue reactivity has been investigated in several fMRI studies. We combined the results of these studies using activation likelihood estimation, a meta-analytic technique for fMRI data. Results of the meta-analysis indicated that smoking cues reliably evoke larger fMRI responses than neutral cues in the extended visual system, precuneus, posterior cingulate gyrus, anterior cingulate gyrus, dorsal and medial prefrontal cortex, insula, and dorsal striatum. Subtraction meta-analyses revealed that parts of the extended visual system and dorsal prefrontal cortex are more reliably responsive to smoking cues in deprived smokers than in non-deprived smokers, and that short-duration cues presented in event-related designs produce larger responses in the extended visual system than long-duration cues presented in blocked designs. The areas that were found to be responsive to smoking cues agree with theories of the neurobiology of cue reactivity, with two exceptions. First, there was a reliable cue reactivity effect in the precuneus, which is not typically considered a brain region important to addiction. Second, we found no significant effect in the nucleus accumbens, an area that plays a critical role in addiction, but this effect may have been due to technical difficulties associated with measuring fMRI data in that region. The results of this meta-analysis suggest that the extended visual system should receive more attention in future studies of smoking cue reactivity.

Beyond cue reactivity: blunted brain responses to pleasant stimuli predict long-term smoking abstinence.

Identifying addicts with higher risk of relapse would provide the opportunity to implement individualized interventions and increase cessation success rates. Unfortunately, the ability to predict the long-term success of drug cessation treatments continues to elude researchers. We tested whether brain responses to emotional and cigarette-related pictures were predictive of the ability to abstain from smoking. Smokers interested in quitting (n=180) participated in a smoking cessation clinical trial. Before the initiation of any treatment, we recorded event-related potentials (ERPs) evoked by emotional (both pleasant and unpleasant), neutral, and cigarette-related images. Cluster analysis was used to assign smokers to two groups based on the amplitude of the late positive potential (LPP) to the experimental stimuli. While both groups showed enhanced responses to cigarette-related cues, one group (n=81) also showed blunted brain responses to intrinsically pleasant stimuli. Smokers in the latter group were significantly less likely to be abstinent at 10, 12 and 24 weeks after their quit date. In conclusion, using ERPs, a direct measure of brain activity, we found that smokers with blunted brain responses to intrinsically pleasant stimuli had lower rates of long-term smoking abstinence. This response offers a new biomarker for identifying smokers at higher risk of relapse and for testing the efficacy of new interventions aimed at normalizing brain reward systems' responses to intrinsically pleasant stimuli.

Sustained reduction of attentional bias to smoking cues by smartphone-delivered attentional bias modification training for smokers.

OBJECTIVE: Cigarette smoking is thought to be at least partially maintained by the attentional bias (AB) toward smoking cues that develops as a consequence of drug dependence. This study evaluated the impact of smartphone-delivered, in-home attentional bias modification (ABM) to reduce AB to smoking cues and to reduce smoking behavior and withdrawal-related symptoms when used as an adjunct to conventional smoking cessation treatment. METHOD: Participants (N = 246) were treatment-seeking smokers who completed up to 13 days of either ABM designed to train attention away from smoking cues, using a modified dot-probe task, or sham training, followed by 8 weeks of nicotine replacement therapy and counseling. Outcomes measured at baseline, 1-day post-ABM training, and 8 weeks post-ABM training included AB to smoking images and words using the dot-probe and smoking Stroop tasks, respectively, along with cigarettes per day, craving, and smoking abstinence. RESULTS: We found that ABM training reduced AB to smoking stimuli on both the dot-probe task, ηp² = 0.056, 90% CI [0.024, 0.097], and the smoking Stroop task, ηp² = 0.017, 90% CI [0.002, 0.044], up to 8 weeks after ABM training when covarying for baseline response, but did not concurrently decrease smoking behavior or craving. CONCLUSIONS: Thirteen days of smartphone-delivered ABM training, as an adjunct to smoking cessation treatment, reduced AB to both modality-specific and cross-modality smoking cues but did not impact smoking-related behavior. While ABM can reduce AB to smoking cues across modalities, it is unclear whether it has therapeutic potential as an adjunct to conventional smoking cessation therapy. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Do brain responses to emotional images and cigarette cues differ? An fMRI study in smokers.

Chronic smoking is thought to cause changes in brain reward systems that result in overvaluation of cigarette-related stimuli and undervaluation of natural rewards. We tested the hypotheses that, in smokers, brain circuits involved in emotional processing: (i) would be more active during exposure to cigarette-related than neutral pictures; and (ii) would be less active to pleasant compared with cigarette-related pictures, suggesting a devaluation of intrinsically pleasant stimuli. We obtained whole-brain blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging data from 35 smokers during the presentation of pleasant (erotica and romance), unpleasant (mutilations and sad), neutral, and cigarette-related pictures. Whole-brain analyses showed significantly larger BOLD responses during presentation of cigarette-related pictures relative to neutral ones within the secondary visual areas, the cingulate gyrus, the frontal gyrus, the dorsal striatum, and the left insula. BOLD responses to erotic pictures exceeded responses to cigarette-related pictures in all clusters except the insula. Within the left insula we observed larger BOLD responses to cigarette-related pictures than to all other picture categories. By including intrinsically pleasant and unpleasant pictures in addition to neutral ones, we were able to conclude that the presentation of cigarette-related pictures activates brain areas supporting emotional processes, but we did not find evidence of overall reduced activation of the brain reward systems in the presence of intrinsically pleasant stimuli.

The impact of nicotine dose and instructed dose on smokers' implicit attitudes to smoking cues: An ERP study.

It is unclear whether nicotine and perceived nicotine exposure can influence automatic evaluations of cigarette stimuli. In the present study, we investigated the effects of nicotine dose and instructed dose on motivational responses to smoking cues. Forty overnight nicotine-deprived smokers completed an Implicit Association Test (IAT) at each of the four laboratory sessions in a balanced-placebo design that crossed nicotine dose (Given-NIC [given nicotine] vs. Given-DENIC [given denicotinized]) with instructed dose expectancy (Told-NIC [told-nicotine] vs. Told-DENIC. [told-denicotinized]). We measured participants' behavioral performance, including reaction time (RT) and accuracy rate, and the early posterior negativity (EPN) component using the event-related potential (ERP) technique to the target pictures. During congruent trials when the categorization condition was smoking or unpleasant, smokers had greater classification accuracy, shorter RT latency, and greater EPN amplitudes compared to the incongruent trials when the categorization condition was smoking or pleasant. The Given-NIC condition was associated with increased classification accuracy, longer RT latency, and decreased EPN amplitudes compared to the Given-DENIC condition. Similarly, the Told-NIC condition was associated with increased accuracy and decreased EPN amplitudes compared to the Told-DENIC condition, but with shorter RT latency. Cigarette-related pictures produced greater EPN amplitudes than neutral pictures. Both behavioral and ERP results suggest that smokers have negative implicit attitudes toward smoking. While both nicotine dose and expected dose facilitated stimulus categorization, there was no evidence that either factor altered smokers' negative attitudes toward smoking cues. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

The Late Positive Potentials Evoked by Cigarette-Related and Emotional Images Show no Gender Differences in Smokers.

When trying to quit, women are less likely than men to achieve long-term smoking abstinence. Identifying the neuropsychological mechanisms underlying women's higher relapse vulnerability will help clinicians to develop effective tailored smoking cessation interventions. Here we used event-related potentials (ERPs), a direct measure of brain activity, to evaluate the extent to which neurophysiological responses to cigarette-related and other emotional stimuli differ between female and male smokers. Both women and men showed similar patterns of brain reactivity across all picture categories; pleasant and unpleasant images prompted larger Late Positive Potentials (LPPs, a robust measure of motivational relevance) than neutral images in both groups, and cigarette-related images prompted lower LPPs than high arousing emotional images in both groups. Unlike previous studies, there were no differences between male and female smokers with regard to LPP responses to cigarette-related images. This suggests that the LPP may not be ideally suited to discriminate neurophysiological gender differences or that there are simply no gender differences in the neurophysiological responses to cigarette-related stimuli. We collected ERPs from 222 non-nicotine-deprived smokers (101 women) while they watched a slideshow that included high and low emotionally arousing pleasant and unpleasant pictures, cigarette-related, and neutral pictures. We used the mean amplitude of the LPP to assess the affective significance that participants attributed to these pictures.

Pharmacological intervention and abstinence in smokers undergoing cessation treatment: A psychophysiological study.

As a composite concept, negative affect comprises various aversive emotional experiences, such as irritability and nervousness. It is a critical motivational factor that helps maintain smoking behavior, and contributes significantly to smoking cessation failure as a core withdrawal symptom. Prior research has indicated an important role of nicotinic mechanisms in negative affect processing. The most effective smoking cessation medication, varenicline, targets nicotinic acetylcholine receptors (nAChRs) as a partial agonist, while another first-line cessation medication, bupropion, has shown antagonistic effects on nAChRs. Therefore, it is possible that both medications work to reduce smoking behavior through modulating negative affect processing. To evaluate this hypothesis, we examined the impact of varenicline tartrate and bupropion hydrochloride sustained-release on electrophysiological responses to affective, cigarette-related, and neutral cues before and during smoking cessation treatment in a randomized placebo-controlled clinical trial. The participants were 206 smokers, a subset of 294 participants that were enrolled in a larger smoking cessation clinical trial who were randomly assigned to one medication group for 12weeks. Orbicularis oculi (startle eyeblink response) and corrugator supercilii facial electromyographic (EMG) reactivity toward emotional pictures (i.e., pleasant and unpleasant) in a picture-viewing task were measured before treatment and 2 and 6weeks after treatment was started. The startle and corrugator EMG activities increase with the exposure to unpleasant cues, and served as indices for negative emotional reactivity (NER). We found that after 6weeks, drug reduced startle-related NER in the varenicline group, but not in the bupropion or placebo group. Independent of medication treatment, lower baseline NER, as measured by the corrugator EMG activity, predicted a higher likelihood of smoking abstinence 1 and 3months after quitting smoking. These findings indicate the important roles of varenicline in negative affect processing and negative emotional reactivity in the course of smoking cessation.

An RCT with the combination of varenicline and bupropion for smoking cessation: clinical implications for front line use.

BACKGROUND AND AIMS: Despite the availability of several efficacious smoking cessation treatments, fewer than 25% of smokers who quit remain abstinent 1 year post-treatment. This study aimed to determine if varenicline and bupropion combination treatment would result in higher abstinence rates than varenicline alone. DESIGN: A double-blind, randomized, parallel-group smoking cessation clinical trial in which participants were exposed to 12 weeks of treatment and followed for 12 months. SETTING: Hospital-based out-patient clinic in Texas, USA specializing in cancer prevention. PARTICIPANTS: A total of 385 community smokers (58.44% male) who smoked 1 pack of cigarettes/day [mean = 19.66 cigarettes/day, standard deviation (SD) = 9.45]; had average carbon monoxide (CO) of 26.43 parts per million (SD = 13.74); and were moderately dependent (Fagerström Test for Cigarette Dependence = 4.79; SD = 2.07). INTERVENTIONS AND COMPARATOR: Smokers were randomized in a 3 : 1 (active: Placebo) ratio to 12 weeks of treatment as follows: placebo (n = 56), varenicline (Var; n = 166), and varenicline + bupropion (Combo; n = 163). MEASUREMENTS: A priori primary outcome: prolonged abstinence at 12 months. SECONDARY OUTCOMES: 7-day point prevalence abstinence and continuous abstinence; all abstinence measures at end of treatment and 6-month follow-ups. FINDINGS: Intention-to-treat analysis: the Combo group (n = 163) failed to demonstrate superiority to the Var group (n = 166) for prolonged abstinence at 12 months [odds ratio (OR) = 0.91, 95% confidence interval (CI) = 0.50-1.64], supported by Bayes factor = 0.06. Both the Var (OR = 6.66, 95% CI = 1.61-59.27) and Combo groups (OR = 6.06, 95% CI = 1.45-54.09) demonstrated superiority to the Placebo group (n = 56; score = 8.38, P < 0.016). CONCLUSIONS: The addition of bupropion to varenicline treatment does not appear to increase smoking abstinence rates above that of varenicline alone. The findings support previous research showing a consistently favorable effect of both varenicline and the combination of varenicline and bupropion on smoking cessation compared with placebo.

Benefits of varenicline vs. bupropion for smoking cessation: a Bayesian analysis of the interaction of reward sensitivity and treatment.

RATIONALE: We have shown that differences in the level of neural activation to stimuli associated with smoking vs. natural rewards, a biomarker related to reward sensitivity, predict treatment outcome. OBJECTIVES: This paper examined whether this biomarker moderates the impact of bupropion or varenicline on smoking cessation. METHODS: Prior to treatment randomization, smokers (N = 180) in a placebo-controlled trial using bupropion and varenicline completed event-related potential recording (late positive potential, LPP) while viewing pleasant (P), cigarette (C)-related, and other pictures. We used Bayesian models to estimate the probability of interaction between treatment and the LPP for both efficacy and comparative effectiveness analyses. RESULTS: Efficacy analysis showed that smokers with more neural activation to pleasant vs. cigarette-related stimuli (P > C) had a 98-99% chance of achieving greater abstinence than placebo (OR >1.00), using either medication from the end of treatment (EOT, primary outcome) through the 3-month follow-up. Relative to placebo, smokers with higher activation to cigarette-related vs. pleasant stimuli (C > P) had a 99% chance of increased benefit from varenicline at both time points (OR >1), but only 67 and 43% with bupropion at the EOT and 3-month follow-up, respectively. Comparative effectiveness analysis found that smokers with the C > P activation pattern had a 95-98% chance of benefit from varenicline vs. bupropion, while P > C smokers had a 50-58% chance of similar improvement with varenicline at the EOT and 3 months. CONCLUSIONS: Varenicline appears to be the treatment of choice for smokers with the C > P pattern of neural activation, while for those showing P > C, varenicline and bupropion have similar efficacy.

Individual differences in brain responses to cigarette-related cues and pleasant stimuli in young smokers.

BACKGROUND: Decreased sensitivity to pleasant stimuli is associated with a higher vulnerability to nicotine dependence in youths and with difficulty quitting in adult smokers. Recently, we showed that smokers showing lower brain reactivity to non-cigarette-related pleasant images than to cigarette-related ones have lower chances of achieving long-term abstinence during a quit attempt. METHODS: We tested whether individual differences in brain responses to cigarette-related and pleasant stimuli require a long history of smoking to develop by measuring the late positive potential (LPP) to cigarette cues, emotional, and neutral stimuli in 45 young, light smokers (ages 18-25). k-means cluster analysis was used to partition smokers into two groups based on the magnitude of their LPPs. RESULTS: Group 1 was characterized by larger LPPs to pleasant pictures than cigarette-related pictures whereas Group 2 showed the opposite pattern. CONCLUSIONS: Our results suggest that individual differences in brain responses to cigarette-related and pleasant cues do not require a long smoking history to develop.

Emotional eating and routine restraint scores are associated with activity in brain regions involved in urge and self-control.

Researchers have proposed a variety of behavioral traits that may lead to weight gain and obesity; however, little is known about the neurocognitive mechanisms underlying these weight-related eating behaviors. In this study, we measured activation of reward circuitry during a task requiring response and inhibition to food stimuli. We assessed participants' emotional eating, external eating, and two subscales of dietary restraint-routine restraint and compensatory restraint-using the Weight-Related Eating Questionnaire. For routine restraint, we found positive associations with activation in the insula, dorsolateral prefrontal cortex, anterior cingulate cortex, orbitofrontal cortex and ventromedial prefrontal cortex in response to high-calorie versus low-calorie foods. For emotional eating, we found positive associations with insula and dorsolateral prefrontal cortex activation in response to high-calorie versus low-calorie foods. We also found positive associations between emotional eating and dorsolateral prefrontal cortex activation in response to approach versus inhibition towards high-calorie foods. Thus, our results demonstrate an increase in activation across brain regions related to self-control and urges in response to high-calorie food associated with both emotional eating and routine restraint. Overall, these results support the construct validity of both emotional eating and routine restraint and provide preliminary evidence that these subscales have similar neural correlates.

Reinforcement sensitivity underlying treatment-seeking smokers' affect, smoking reinforcement motives, and affective responses.

Nicotine dependence has been suggested to be related to reinforcement sensitivity, which encompasses behavioral predispositions either to avoid aversive (behavioral inhibition) or to approach appetitive (behavioral activation) stimuli. Reinforcement sensitivity may shape motives for nicotine use and offer potential targets for personalized smoking cessation therapy. However, little is known regarding how reinforcement sensitivity is related to motivational processes implicated in the maintenance of smoking. Additionally, women and men differ in reinforcement sensitivity, and such difference may cause distinct relationships between reinforcement sensitivity and motivational processes for female and male smokers. In this study, the authors characterized reinforcement sensitivity in relation to affect, smoking-related reinforcement motives, and affective responses, using self-report and psychophysiological measures, in over 200 smokers before treating them. The Behavioral Inhibition/Activation Scales (BIS/BAS; Carver & White, 1994) was used to measure reinforcement sensitivity. In female and male smokers, BIS was similarly associated with negative affect and negative reinforcement of smoking. However, positive affect was positively associated with BAS Drive scores in male smokers, and this association was reversed in female smokers. BIS was positively associated with corrugator electromyographic reactivity toward negative stimuli and left frontal electroencephalogram alpha asymmetry. Female and male smokers showed similar relationships for these physiological measures. These findings suggest that reinforcement sensitivity underpins important motivational processes (e.g., affect), and gender is a moderating factor for these relationships. Future personalized smoking intervention, particularly among more dependent treatment-seeking smokers, may experiment to target individual differences in reinforcement sensitivity. (PsycINFO Database Record

Brain responses to erotic and other emotional stimuli in breast cancer survivors with and without distress about low sexual desire: a preliminary fMRI study.

Many breast cancer survivors report a loss of sexual desire and arousability, consonant with the new DSM-V category of female sexual interest/arousal disorder. The cause of decreased sexual desire and pleasure after treatment for cancer is unknown. One possibility is that cancer, or treatment for cancer, damages brain circuits that are involved in reward-seeking. To test the hypothesis that brain reward systems are involved in decreased sexual desire in breast cancer survivors, we used functional magnetic resonance imaging (fMRI) to compare brain responses to erotica and other emotional stimuli in two groups of women previously treated for breast cancer with chemotherapy: those who were distressed about a perceived loss of sexual desire and those who may have had low desire, but were not distressed about it. Women distressed about their desire had reduced brain responses to erotica in the anterior cingulate and dorsolateral prefrontal cortex, which are part of the brain reward system. This study is the first to demonstrate, in cancer survivors, that problems with sexual desire/arousability are associated with blunted brain responses to erotica in reward systems. Future research is necessary to determine whether brain responses differ as a result of chemotherapy, hormone therapy, and menopausal status. This may contribute to the development of new, evidence-based interventions for one of the most prevalent and enduring side effects of cancer treatment.

The late positive potential (LPP) in response to varying types of emotional and cigarette stimuli in smokers: a content comparison.

Identifying neural mechanisms associated with addiction has substantially improved the overall understanding of addictive processes. Indeed, research suggests that drug-associated cues may take advantage of neural mechanisms originally intended for emotional processing of stimuli relevant to survival. In this study, we investigated cortical responses to several categories of emotional cues (erotic, romance, pleasant objects, mutilation, sadness, and unpleasant objects) as well as two types of smoking-related cues (people smoking and cigarette-related objects). We recorded ERPs from 180 smokers prior to their participation in a smoking cessation clinical trial and assessed emotional salience by measuring the amplitude of the late positive potential (LPP; 400 to 600 ms after picture onset). As expected, emotional and cigarette-related pictures prompted a significantly larger LPP than neutral pictures. The amplitude of the LPP increased as a function of picture arousal level, with high-arousing erotic and mutilation pictures showing the largest response in contrast to low-arousing pleasant and unpleasant objects, which showed the smallest response (other than neutral). Compared to females, male participants showed larger LPPs for high-arousing erotic and mutilation pictures. However, unlike emotional pictures, no difference was noted for the LPP between cigarette stimuli containing people versus those containing only objects, suggesting that in contrast to emotional objects, cigarette-related objects are highly relevant for smokers. We also compared the smokers to a small (N=40), convenience sample of never-smokers. We found that never-smokers had significantly smaller LPPs in response to erotic and cigarette stimuli containing only objects compared to smokers.

Effects of varenicline and bupropion sustained-release use plus intensive smoking cessation counseling on prolonged abstinence from smoking and on depression, negative affect, and other symptoms of nicotine withdrawal.

IMPORTANCE: Given the actions of varenicline tartrate and bupropion hydrochloride sustained-release (SR) on neurobiological targets related to affect and reward, it is thought that the modulation of nicotine withdrawal symptoms may contribute to their effectiveness. OBJECTIVE: To assess the relative efficacy of varenicline and bupropion SR plus intensive counseling on smoking cessation and emotional functioning. DESIGN AND SETTING: Placebo-controlled randomized clinical trial at a university medical center. PARTICIPANTS: In total, 294 community volunteers who wanted to quit smoking. INTERVENTIONS: Twelve weeks of varenicline, bupropion SR, or placebo plus intensive smoking cessation counseling (10 sessions, for a total of approximately 240 minutes of counseling). MAIN OUTCOME MEASURES: Prolonged abstinence from smoking and weekly measures of depression, negative affect, and other symptoms of nicotine withdrawal. RESULTS: Significant differences were found in abstinence at the end of treatment and through the 3-month postquit follow-up visit, favoring both active medications compared with placebo. At the 6-month postquit follow-up visit, only the varenicline vs placebo comparison remained significant. Varenicline use was also associated with a generalized suppression of depression and reduced smoking reward compared with the other treatments, while both active medications improved concentration, reduced craving, and decreased negative affect and sadness compared with placebo, while having little effect (increase or decrease) on anxiety and anger. No differences were noted in self-reported rates of neuropsychiatric adverse events. CONCLUSIONS AND RELEVANCE: In a community sample, varenicline exerts a robust and favorable effect on smoking cessation relative to placebo and may have a favorable (suppressive) effect on symptoms of depression and other affective measures, with no clear unfavorable effect on neuropsychiatric adverse events. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00507728.