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Smokers with stronger neuroaffective responses to drug-related cues compared to nondrug-related pleasant images (C > P) are more vulnerable to compulsive smoking than individuals with the opposite brain reactivity profile (P > C). However, it is unknown if these neurobehavioral profiles exist in individuals abusing other drugs. We tested whether individuals with cocaine use disorder (CUD) show similar neuroaffective profiles to smokers. We also monitored eye movements to assess attentional bias toward cues and we further performed exploratory analyses on demographics, personality, and drug use between profiles. Participants with CUD (n = 43) viewed pleasant, unpleasant, cocaine, and neutral images while we recorded electroencephalogram. For each picture category, we computed the amplitude of the late positive potential (LPP), an event-related potential component that reflects motivational relevance. k-means clustering classified participants based on their LPP responses. In line with what has been observed in smokers, clustering participants using LPP responses revealed the presence of two groups: one with larger LPPs to pleasant images compared to cocaine images (P > C) and one group with larger LPPs to cocaine images compared to pleasant images (C > P). Individuals with the C > P reactivity profile also had higher attentional bias toward drug cues. The two groups did not differ on demographic and drug use characteristics, however individuals with the C > P profile reported lower distress tolerance, higher anhedonia, and higher posttraumatic stress symptoms compared to the P > C group. This is the first study to report the presence of these neuroaffective profiles in individuals with CUD, indicating that this pattern may cut across addiction populations. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Breast Cancer is the most frequently diagnosed cancer among women. Despite the decreasing death-rate, a large portion of patients experience long-term side effects. One of the most common is “chemobrain”: a series of subtle but persistent cognitive deficits that affect attention, memory, and speed of processing. There is a lack of consensus regarding the exact rate of “chemobrain” incidence(from 12% to 86% of patients complaining cognitive sequelae after adjuvant-therapies) primarily due to the heterogeneity of assessment measures used to quantify it. Our first aim was to estimate the prevalence of perceived cognitive deficits in breast cancer-survivors, and to address the relevance of psycho-social factors that might affect perceived cognitive functioning. The second aim was to better understand the specific impact on patients comparing possible differences in perceived cognitive functioning between a cohort of breast cancer-survivors and an age-matched group of women without oncologic diagnosis. A total of 216 subjects submitted an anonymous online questionnaire that included FACTCog v.3and 41 items investigating clinical history, cognitive reserve, sleep quality, dietary and health habits. Inclusion criteria were being female, aged between 25 and 75, lack of known psychiatric or neurological diseases. The study was approved by the Ethical Committee of University of Trieste. The study sample comprised 90 oncological patients, recruited through clinical oncology practices between Trieste - ASU GI and Cremona - ASST Breast Cancer Units, and 126 age-matched controls enrolled through LILT (Lega Italiana Lotta Tumori) - Trieste (Italy). To perform within and between groups comparisons, both populations (Breast-cancer patients’ and age-matched controls’) were subdivided in two subgroups each, based on FACTCog PCI18 score according to Van Dyk et al.(2020), cutpoints: Subjective Cognitive Complaints - SCC (PCI18 Citation Format: Thomas West, Bruna Scaggiante, Rita Ceccherini, Silva Foladore, Daniele Generali, Francesco Versace, Corrado Cavallero. The relevance of chemobrain in breast cancer survivors: An Italian exploratory study to measure incidence and psycho-social impact [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-10-12.

BACKGROUND: There is preliminary evidence that the anticonvulsant topiramate increases the likelihood of both smoking and alcohol abstinence among smokers with alcohol use disorder (AUD), but its therapeutic mechanism has not been determined. We used event-related potentials (ERPs) to evaluate topiramate’s effect on the salience of drug-related, emotional, and neutral pictorial cues to identify whether one of its potential therapeutic mechanisms involves reduction of the salience of motivationally relevant cues. METHODS: Participants, who were enrolled in a multisite clinical trial treating smokers with AUD, were randomized to receive placebo, low-dose topiramate (up to 125 mg/day), or high-dose topiramate (up to 250 mg/day), along with brief behavioral compliance enhancement treatment. A subsample (n=101) completed ERP assessments at baseline (1 week pre-medication) and week 5 (5 weeks on medication; 1 week pre-quit). We assessed the salience of pleasant, unpleasant, cigarette-related, alcohol-related, and neutral pictorial cues using the late positive potential (LPP) ERP component, and measured self-reported substance use, reinforcement, craving, and withdrawal. RESULTS: Five weeks of high-dose topiramate treatment decreased LPP amplitudes to both emotional (pleasant and unpleasant) and drug-related cues (alcohol and cigarette), but not to neutral cues. However, results showed that the LPPs were not significant mediators of the relationship between topiramate dose and post-quit measures of substance use, reinforcement, craving, or withdrawal. CONCLUSIONS: These findings suggest that high-dose topiramate (up to 250 mg/day) decreases the motivational salience of both drug-related and emotional cues among smokers with AUD. However, the nonsignificant mediation analyses preclude any firm conclusions about whether this effect represents one of topiramate’s therapeutic mechanisms of action.

The behavioral economic measure drug demand and the neural measure late positive potential (LPP) are two measures of motivational value that have been associated with drug relapse risk and treatment outcomes. Despite having overlapping themes, no studies have directly compared drug demand and LPP. Participants (

Continuing to eat even when full leads to excessive calorie consumption and obesity. Thus, understanding brain responses to food cues when satiated has important implications for weight control interventions. We used the late positive potential (LPP, a component of the event-related potentials (ERP) indexing motivational relevance) to determine the extent to which satiety affects brain responses to images of highly palatable foods (high-fat, high-sugar), high and low motivationally relevant (pleasant, unpleasant) and neutral stimuli in a sample of obese (body mass index [BMI] ≥ 30 kg/m2) and lean (BMI < 25 kg/m2) individuals. Satiated individuals (N = 55, 21 with BMI ≥ 30 kg/m2) were fed a nutritional drink prior to the experimental session and were individually matched with 55 unsatiated individuals who saw the same images during a passive viewing task. Satiety did not affect LPP response to food-related or motivationally relevant cues in either BMI < 25 kg/m2 or BMI ≥ 30 kg/m2 individuals (p = .6). Irrespective of satiety, all participants showed larger LPPs as a function of the images' motivational relevance. There were no differences in LPP amplitude between BMI < 25 kg/m2 and BMI ≥ 30 kg/m2 individuals for any picture category, including food. However, within-group comparisons showed that BMI < 25 kg/m2 individuals had larger LPPs to low motivationally relevant pleasant images than to food-related cues (p < .001); this difference was not significant for BMI ≥ 30 kg/m2 individuals. Although satiety does not affect LPP responses to food-related cues, these results highlight the importance of evaluating reactivity to food-related cues in relation to other motivationally relevant stimuli. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

To create reproducible emotional probes, affective scientists rely on sets of standardized pictures that are normed using subjective ratings of valence and emotional arousal. However, when emotional responses are investigated using neurophysiological measures, it might be more appropriate to select pictures integrating information from normative subjective reports and normative neurophysiological responses. Here, we provide electrophysiological normative responses for 323 emotional pictures (215 from the IAPS) covering a wide range of categories (erotica, romantic, appetizing foods, landscapes, people engaged in mundane activities, household objects, disgusting objects, accidents, sad people, violence, mutilations, and cigarette-related contents). Event-related potentials (ERPs) and subjective ratings of pleasure and emotional arousal were collected from 763 individuals (52% females, 41% white) aged between 18 and 65 (mean = 43). For each image, the mean amplitude of the late positive potential (LPP, an electrophysiological index of motivational relevance) and the mean subjective ratings of valence and arousal were calculated. We validated our procedure by showing that the subjective ratings of valence and arousal from this sample were highly correlated to the IAPS' published norms (Pearson r = .97 for pleasure and r = .82 for emotional arousal). LPP responses and subjective ratings of emotional arousal also were correlated (Pearson r = .61), but some categories reported being significantly more arousing than neutral (i.e., food, landscapes, and unpleasant objects) did not evoke LPPs significantly different from those evoked by neutral pictures. Researchers interested in probing the brain's affective systems can use these electrophysiological normative responses to create emotional probes that evoke reliable neuroaffective responses.

To create reproducible emotional probes, affective scientists rely on sets of standardized pictures that are normed using subjective ratings of valence and emotional arousal. Yet, to investigate psychophysiological emotional responses, it might be more appropriate to select pictures using normative neurophysiological responses rather than normative subjective ratings. Here, we provide electrophysiological normative responses for 323 emotional pictures (215 from the IAPS) covering a wide range of categories (erotica, romantic, appetizing foods, landscapes, people engaged in mundane activities, household objects, disgusting objects, accidents, sad people, violence, mutilations, and cigarette-related contents). Event-related potentials (ERPs) and subjective ratings of pleasure and emotional arousal were collected from 763 individuals (52% females, 41% white) aged between 18 and 65 (mean = 43). For each image, the mean amplitude of the late positive potential (LPP, an electrophysiological index of motivational relevance) and the mean subjective ratings of valence and arousal were calculated. We validated our procedure by showing that the subjective ratings of valence and arousal from this sample were highly correlated to the IAPS’ published norms (Pearson r=.97 for pleasure and r=.82 for emotional arousal). LPP responses and subjective ratings of emotional arousal also were correlated (Pearson r = .61), but some categories that participants reported being significantly more arousing than neutral (i.e., food, landscapes, and unpleasant objects) did not evoke LPPs significantly different from those evoked by neutral pictures. Researchers interested in probing the brain’s affective systems can use these electrophysiological normative responses to create emotional probes that evoke reliable neuroaffective responses.

Both the brain's reward and cognitive control systems are known to regulate cue-induced eating. Although it is established that individual differences in affective processing of food-related cues predict cue-induced eating, we have yet to investigate how both affective and cognitive mechanisms act in tandem to regulate cue-induced eating. In the present study, our goal was to characterize the mechanisms that make some individuals vulnerable to cue-induced eating while leaving others resilient. We recorded electroencephalogram (EEG) from 59 adults while they viewed emotional & food-related images that preceded the delivery of food rewards (candies) or nonfood objects (beads [control]). We measured the amplitude of the late positive potential (LPP; a measure of motivational salience) in response to the images and power in the theta (4-8 Hz) frequency band (a measure of cognitive control) after the candy or bead was dispensed to the participant. We found that individuals with larger LPP responses to food cues than to pleasant images (C>P group) ate significantly more during the experiment than did those with larger LPP responses to pleasant images than to food cues (P>C group, p < 0.001). Furthermore, we found that individuals with higher theta power after dispensation of the candy than of the bead (CA>BE) ate significantly more than did those with higher theta power after dispensation of the bead than of the candy (BE>CA, p < 0.001). Finally, we found that the crossed P>C and BE>CA group ate less (p < 0.001) than did the other three groups formed by crossing the LPP and theta group assignments, who exhibited similar eating behavior on average (p = 0.662). These findings demonstrate that motivational salience and cognitive control converge to independently confer vulnerability or resilience to cue-induced behaviors, underscoring the need for individualized treatments to mitigate maladaptive behaviors.

IntroductionIdentifying the psychophysiological underpinnings of cue-induced compulsive nicotine use will provide new targets for relapse prevention treatments. We tested whether neuroaffective responses to motivationally relevant stimuli are associated with cue-induced nicotine self-administration. We hypothesized that smokers with stronger neuroaffective responses to nicotine-related cues than to pleasant stimuli (C>P) are more vulnerable to cue-induced nicotine self-administration than smokers with stronger neuroaffective responses to pleasant stimuli than to nicotine-related cues (P>C).MethodsSmokers (N=36) looked at pleasant, unpleasant, neutral, and nicotine-related images signaling that an electronic nicotine delivery system (ENDS) was immediately available for use. We measured event-related potentials (a direct measure of cortical activity) and computed the amplitude of the late positive potential, a robust index of motivational salience. We used k-means cluster analysis to identify individuals characterized by the C>P or the P>C neuroaffective profile. We compared the ENDS use frequency in the two groups using quantile regression for counts.ResultsCluster analysis assigned 18 smokers to the C>P profile and 18 smokers to the P>C profile. Smokers with the C>P neuroaffective profile used the ENDS significantly more often than smokers with the P>C profile. Significant differences in the number of puffs persisted across different quantiles.ConclusionsThese results support the hypothesis that individual differences in the tendency to attribute motivational salience to drug-related cues underlie vulnerability to cue-induced drug self-administration.ImplicationsBy linking brain reactivity profiles to nicotine self-administration, we identified a neuroaffective biomarker that could guide the development of personalized treatments to prevent smoking relapse.

Anhedonia (i.e., the attenuated ability to enjoy pleasurable stimuli) characterizes multiple mood disorders, but its neurophysiological underpinnings are not yet clear. Here, we measured event-related potentials in 116 adolescents and young adults engaged in an asymmetric reinforcement procedure designed to objectively characterize the anhedonic phenotype. In line with previous studies, the behavioral results showed that approximately 35% of the sample did not develop a response bias towards the more frequently rewarded stimuli (a sign of low hedonic capacity). The event-related potentials (ERPs) evoked by the reward feedback stimuli delivered during the task showed that individuals that did not develop a response bias had less cortical positivity at Fz from 224 ms to 316 ms post feedback onset compared to those that developed a response bias during the task. However, further analyses showed that this between groups difference was relatively weak, as it disappeared when we controlled for response-locked ERPs. Furthermore, the response bias observed in the asymmetric reinforcement procedure was not strongly associated with self-reported ratings of hedonic capacity. We conclude that even though the asymmetric reinforcement procedure may be used as a reward sensitivity measure in neurotypical adolescents and young adults, this task may only be able to detect clinically significant levels of anhedonia in this particular population.

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.

Event-related potentials (ERPs) summarize electrophysiological brain response to specific stimuli. They can be considered as correlated functions of time with both spatial correlation across electrodes and nested correlations within subjects. Commonly used analytical methods for ERPs often focus on pre-determined extracted components and/or ignore the correlation among electrodes or subjects, which can miss important insights, and tend to be sensitive to outlying subjects, time points or electrodes. Motivated by ERP data in a smoking cessation study, we introduce a Bayesian spatial functional regression framework that models the entire ERPs as spatially correlated functional responses and the stimulus types as covariates. This novel framework relies on mixed models to characterize the effects of stimuli while simultaneously accounting for the multilevel correlation structure. The spatial correlation among the ERP profiles is captured through basis-space Matern assumptions that allow either separable or nonseparable spatial correlations over time. We induce both adaptive regularization over time and spatial smoothness across electrodes via a correlated normal-exponential-gamma (CNEG) prior on the fixed effect coefficient functions. Our proposed framework includes both Gaussian models as well as robust models using heavier-tailed distributions to make the regression automatically robust to outliers. We introduce predictive methods to select among Gaussian vs. robust models and models with separable vs. non-separable spatiotemporal correlation structures. Our proposed analysis produces global tests for stimuli effects across entire time (or time-frequency) and electrode domains, plus multiplicity-adjusted pointwise inference based on experiment-wise error rate or false discovery rate to flag spatiotemporal (or spatio-temporal-frequency) regions that characterize stimuli differences, and can also produce inference for any prespecified waveform components. Our analysis of the smoking cessation ERP data set reveals numerous effects across different types of visual stimuli.

It has been proposed that some individuals succumb to maladaptive eating behaviors because, like those with addiction, they attribute high incentive salience to food-associated cues. Here, we tested whether women that attribute high incentive salience to food-associated cues report high food addiction symptomatology. In 76 college women, we assessed self-reported food addiction symptoms using the Yale Food Addiction Scale and we recorded event-related potentials (ERPs, a direct measure of brain activity) to preferred food, erotic, unpleasant, and neutral images. We used the amplitude of the late positive potential (LPP, a component of the ERPs) as an index of the incentive salience attributed to the images. Using a multivariate classification algorithm (k-means cluster analysis), we identified two neuroaffective reactivity profiles that have been previously associated with individual differences in the tendency to attribute incentive salience to cues and with differences in vulnerability to addictive behaviors. Results showed that women with elevated LPP responses to preferred food cues relative to erotic images report higher food addiction symptoms than women with low LPP responses to preferred food cues relative to other motivationally relevant stimuli. These results support the hypothesis that individual differences in the tendency to attribute incentive salience to food cues play an important role in modulating food addiction symptomatology.

Background The properties of neurophysiological processes related to addiction have received much attention in the literature. However, empirical evidence of meaningful and useful characterization of these processes is limited. Recent studies have found that electrophysiological responses to emotional and drug-related cues can be used to create profiles that reliably predict smoking relapse. New method This paper evaluates the validity of classifying electrophysiological responses into distinct profiles using a Bayesian dirichlet process mixture (DPM) model. The DPM is a Bayesian nonparametric (BNP) method to modeling unknown number of profiles characterized by uncertainty in cluster membership and in cluster number. Results The DPM model confirmed previously identified neuroaffective reactivity profiles, but also revealed a finer level of granularity in the clustering. Specifically, in addition to the two clusters previously identified in the literature, the BNP methods identified a cluster of individuals showing similar responses to smoking, pleasant, neutral and unpleasant cues. Comparison with existing methods BNP models provide an alternative to the k-mean clustering approach to modeling EEG-based neuroaffective profiles. Unlike k-means clustering, BNP models compute the probability that a subject belongs to a cluster while taking into consideration uncertainty in the number of clusters. Conclusions Our results confirm the reliability of the two clusters previously identified in these data, but also provide new insights by revealing a cluster that presented similar responses to stimuli with different contents. This finding may be related to the uncertainty in classification or overlapping brain-reactivity profiles.

Introduction By improving our understanding of the neurobiological mechanisms underlying addiction, neuroimaging research is helping to identify new targets for personalized treatment interventions. When trying to quit, smokers with larger electrophysiological responses to cigarette-related, compared with pleasant, stimuli (“C > P”) are more likely to relapse than smokers with the opposite brain reactivity profile (“P > C”). Aim and Method The goal was to (1) build a classification algorithm to identify smokers characterized by P > C or C > P neuroaffective profiles and (2) validate the algorithm’s classification outcomes in an independent data set where we assessed both smokers’ electrophysiological responses at baseline and smoking abstinence during a quit attempt. We built the classification algorithm applying discriminant function analysis on the event-related potentials evoked by emotional images in 180 smokers. Results The predictive validity of the classifier showed promise in an independent data set that included new data from 177 smokers interested in quitting; the algorithm classified 111 smokers as P > C and 66 as C > P. The overall abstinence rate was low; 15 individuals (8.5% of the sample) achieved CO-verified 12-month abstinence. Although individuals classified as P > C were nearly 2.5 times more likely to be abstinent than smokers classified as C > P (12 vs. 3, or 11% vs. 4.5%), this result was nonsignificant, preliminary, and in need of confirmation in larger trials. Conclusion These results suggest that psychophysiological techniques have the potential to advance our knowledge of the neurobiological underpinnings of nicotine addiction and improve clinical applications. However, larger sample sizes are necessary to reliably assess the predictive ability of our algorithm. Implications We assessed the clinical relevance of a neuroimaging-based classification algorithm on an independent sample of smokers enrolled in a smoking cessation trial and found those with the tendency to attribute more relevance to rewards than cues were nearly 2.5 times more likely to be abstinent than smokers with the opposite brain reactivity profile (11% vs. 4.5%). Although this result was not statistically significant, it suggests our neuroimaging-based classification algorithm can potentially contribute to the development of new precision medicine interventions aimed at treating substance use disorders. Regardless, these findings are still preliminary and in need of confirmation in larger trials.

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 (Fagerstrom 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 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.

Background While the notion that smokers reliably show higher reactivity to cigarette-related versus neutral cues is both theoretically and empirically supported, it is unclear why never-smokers also show enhanced brain responses to cigarette-related cues. Methods Using a repetitive picture viewing paradigm, in which responses evoked by affective cues are more resistant to habituation, we assessed the effects of stimulus repetition on event-related potentials (ERPs) evoked by pleasant, unpleasant, cigarette-related, and neutral images in 34 smokers (SMO) and 34 never-smokers (NEV). We examined the early posterior negativity (EPN) and the late positive potential (LPP), two ERP components which are sensitive to a picture's motivational qualities. Results Before stimulus repetition, pleasant, unpleasant, and cigarette-related cues produced greater EPN and LPP amplitudes than neutral cues in all subjects. During stimulus repetition, both components were similarly modulated by emotional arousal, such that pleasant, unpleasant, and cigarette-related cues evoked greater EPN and LPP amplitude, relative to neutral. Smoking status did not modulate these effects. While there were no group differences in self-reported stimulus ratings of valence for pleasant, unpleasant, or neutral stimuli, NEV rated cigarette-related cues as unpleasant. We observed a moderate, negative correlation between LPP amplitude and self-reported valence ratings of cigarette-related cues among NEV. Conclusions These data suggest that cigarette-related cues capture attentional resources of both SMO and NEV, but for different reasons. For SMO, cigarette-related cues have acquired motivational significance through repeated associations with nicotine delivery, whereas for NEV, cigarette-related cues are perceived as unpleasant.

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.

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.

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. This paper examined whether this biomarker moderates the impact of bupropion or varenicline on smoking cessation. 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. 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. 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.

The late positive potential (LPP) is a common measurement used to study emotional processes of subjects in event-related potential (ERP) paradigms. Despite its extensive use in affective neuroscience, there is presently no gold standard for how to appropriately power ERP studies using the LPP in within-subject and between-subjects experimental designs. The present study investigates how the number of trials, number of subjects, and magnitude of the effect size affect statistical power in analyses of the LPP. Using Monte Carlo simulations of ERP experiments with varying numbers of trials, subjects, and effect sizes, we measured the probability of obtaining a statistically significant effect in 1,489 different experiments repeated 1,000 times each. Predictably, our results showed that statistical power increases with increasing numbers of trials and subjects and at larger effect sizes. In addition, we found that higher levels of statistical power can be achieved with lower numbers of subjects and trials and at lower effect sizes in within-subject than in between-subjects designs. Furthermore, we found that, as subjects are added to an experiment, the slope of the relationship between effect size and statistical power increases and shifts to the left until the power asymptotes to nearly 100% at higher effect sizes. This suggests that adding more subjects greatly increases statistical power at lower effect sizes (1.5 µV) effect sizes.

The late positive potential (LPP) is a common measurement used to study emotional processes of subjects in event-related potential (ERP) paradigms. Despite its extensive use in affective neuroscience, there is presently no gold standard for how to appropriately power ERP studies using the LPP. The present study investigates how the number of trials, number of subjects, and magnitude of the effect size affect statistical power in analyses of the LPP. Using Monte Carlo simulations of ERP experiments with varying numbers of trials, subjects, and synthetic effects of known magnitude, we measured the probability of obtaining a statistically significant effect in 1,489 experiments repeated 1,000 times each. Predictably, our results showed that statistical power increases with increasing numbers of trials and subjects and at larger effect sizes. We also found that higher levels of statistical power can be achieved with lower numbers of subjects and trials and at lower effect sizes in within-subject than in between-subjects designs. Furthermore, we found that as subjects are added to an experiment, the slope of the relationship between effect size and statistical power increased and shifted to the left until the power asymptoted to nearly 100% at higher effect sizes. This suggests that adding more subjects greatly increases statistical power at lower effect sizes (1.5 μV) effect sizes. We confirmed the results from the simulations based on the synthetic effects by running a new series of simulated experiments based on real data collected while participants looked at emotional images.

While some individuals can defy the lure of temptation, many others find appetizing food irresistible. The goal of this study was to investigate the neuropsychological mechanisms that increase individuals' vulnerability to cue‐induced eating. Using ERPs, a direct measure of brain activity, we showed that individuals with larger late positive potentials in response to food‐related cues than to erotic images are more susceptible to cue‐induced eating and, in the presence of a palatable food option, eat more than twice as much as individuals with the opposite brain reactivity profile. By highlighting the presence of individual brain reactivity profiles associated with susceptibility to cue‐induced eating, these findings contribute to the understanding of the neurobiological basis of vulnerability to obesity., Our findings contribute to the understanding of the biological bases underlying individual differences in vulnerability to cue‐induced eating, and they represent a step toward identifying new targets for personalized weight control interventions.

Anhedonia (i.e., the attenuated ability to enjoy pleasurable stimuli) characterizes multiple mood disorders, but its neurophysiological underpinnings are not yet clear. Here, we measured event-related potentials in 116 adolescents and young adults engaged in a signal detection task designed to objectively characterize the anhedonic phenotype. In line with previous studies, the behavioral results showed that approximately 35% of the sample did not develop a response bias towards the more frequently rewarded stimuli (a sign of low hedonic capacity). The event-related potentials (ERPs) evoked by the reward feedback stimuli delivered during the task showed that individuals that did not develop a response bias had significantly less cortical positivity at Fz from 224 ms to 316 ms post feedback onset compared to those that developed a response bias during the task. However, further analyses showed that this between groups difference was relatively weak, as it disappeared when we controlled for response-locked ERPs. Furthermore, the response bias observed in the signal detection task was not strongly associated with self-reported ratings of hedonic capacity. We conclude that even though the signal detection task may be used as a reward sensitivity measure in neurotypical adolescents and young adults, this task may only be able to detect clinically significant levels of anhedonia in this particular population.

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.

Through Pavlovian conditioning, reward-associated neutral stimuli can acquire incentive salience and motivate complex behaviors. In smokers, cigarette-associated cues may induce cravings and trigger smoking. Understanding the brain mechanisms underlying conditioned responses to cigarette-associated relative to other inherently pleasant stimuli might contribute to the development of more effective smoking cessation treatments that emphasize the rehabilitation of reward circuitry. Here we measured brain responses to geometric patterns (the conditioned stimuli, CSs) predicting cigarette-related, intrinsically pleasant and neutral images (the unconditioned stimuli, USs) using event-related potentials (ERPs) in 29 never-smokers, 20 nicotine-deprived smokers, and 19 non-deprived smokers. Results showed that during US presentation, cigarette-related and pleasant images prompted higher cortical positivity than neutral images over centro-parietal sensors between 400 and 800 ms post-US onset (late positive potential, LPP). The LPP evoked by pleasant images was significantly larger than the LPP evoked by cigarette images. During CS presentation, ERPs evoked by geometric patterns predicting pleasant and cigarette-related images had significantly larger amplitude than ERPs evoked by CSs predicting neutral images. These effects were maximal over right parietal sites between 220 and 240 ms post-CS onset and over occipital and frontal sites between 308 and 344 ms post-CS onset. Smoking status did not modulate these effects. Our results show that stimuli with no intrinsic reward value (e.g., geometric patterns) may acquire rewarding properties through repeated pairings with established reward cues (i.e., cigarette-related, intrinsically pleasant).

over a grid|is frequently obtained. Moreover, researchers often sample multiple curves per person resulting in repeated functional measures. A common question is how to analyze the relationship between two functional variables. We propose a general function-on-function regression model for repeatedly sampled functional data on a ne grid, presenting a simple model as well as a more extensive mixed model framework, and introducing various functional Bayesian inferential procedures that account for multiple testing. We examine these models via simulation and a data analysis with data from a study that used event-related potentials to examine how the brain processes various types of images.

Graphical abstract Representative diagram of the experimental setup. The laboratory control computer (A) triggers the dispensing device (B) to dispense either a food (candy) or non-food control item in the delivery receptacle (C). The participant may either eat the candy, or deposit the candy or non-food control item in the appropriate deposit box (D). The display of the master laboratory computer (A) is mirrored in the participant laboratory room (E), and displays pictorial stimuli predicting either the food reward or non-food control item. During the experiment, the electroencephalogram (EEG) is being recorded and is displayed on a computer (F) in the laboratory control room. The master computer (A) sends triggers to the EEG computer (F) to allow subsequent time-locking of events. Blue arrows represent information flow from the participant laboratory room to the laboratory control room. Black arrows represent information flow from the laboratory control room to the participant laboratory room., Neurobiological models of obesity postulate that obese individuals have difficulty regulating food intake partly because they attribute excessive salience to stimuli signaling food availability. Typically, human studies that investigate the relationship between brain responses to food-related stimuli and obesity present food cues without subsequent delivery of food. However, in order to identify the brain correlates of cue reactivity, we must record brain responses to food-related cues signaling food availability. Therefore, we have developed a dispensing apparatus for use in a cued-food delivery task in which event-related potentials (ERPs) to food-related images predicting food delivery and images not predicting food delivery can be recorded. Here, we describe a method where:•The experimental apparatus dispenses an edible item (i.e., a chocolate candy) which may or may not be eaten, or a non-edible control item (e.g., a plastic bead).•Deposit boxes are available to store uneaten candies and the non-edible control items.•The dispensing mechanism is capable of recording the exact timestamp when each delivery event occurs (e.g., release from the dispenser, arrival in the receptacle, storage in the deposit box).

While some individuals can defy the lure of temptation, many others find appetizing food irresistible. The goal of this study was to investigate the neuropsychological mechanisms that increase individuals' vulnerability to cue-induced eating. Using ERPs, a direct measure of brain activity, we showed that individuals with larger late positive potentials in response to food-related cues than to erotic images are more susceptible to cue-induced eating and, in the presence of a palatable food option, eat more than twice as much as individuals with the opposite brain reactivity profile. By highlighting the presence of individual brain reactivity profiles associated with susceptibility to cue-induced eating, these findings contribute to the understanding of the neurobiological basis of vulnerability to obesity.

BACKGROUND AND AIMS: Despite the availability of several efficacious smoking cessation treatments, less 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 groups smoking cessation clinical trial in which participants were exposed to 12 weeks of treatment and followed for 12 months. SETTING: Hospital-based outpatient clinic in Texas, USA specializing in cancer prevention. PARTICIPANTS: 385 community smokers (56% male) who smoked 1 pack cigarettes/day (Mean = 19.66 cigs/day, S.D. = 9.45); had an average CO of 26.43 ppm (S.D. =13.74); and were moderately dependent (FTCD = 4.79; S.D. = 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: Seven-day point prevalence abstinence and continuous abstinence; all abstinence measures at end of treatment and 6 month follow-ups. FINDINGS: Intent 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 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.

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.

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.

In this paper we propose a unified, probabilistically coherent framework for the analysis of task-related brain activity in multi-subject fMRI experiments. This is distinct from two-stage “group analysis” approaches traditionally considered in the fMRI literature, which separate the inference on the individual fMRI time courses from the inference at the population level. In our modeling approach we consider a spatiotemporal linear regression model and specifically account for the between-subjects heterogeneity in neuronal activity via a spatially informed multi-subject nonparametric variable selection prior. For posterior inference, in addition to Markov chain Monte Carlo sampling algorithms, we develop suitable variational Bayes algorithms. We show on simulated data that variational Bayes inference achieves satisfactory results at more reduced computational costs than using MCMC, allowing scalability of our methods. In an application to data collected to assess brain responses to emotional stimuli our method correctly detects activation in visual areas when visual stimuli are presented.

We investigated the effects of acute nicotine dose and expected dose on attentional bias (AB) to smoking and affective cues in overnight nicotine-deprived smokers ( n=51; 24 women) using a balanced placebo design, which counterbalanced given nicotine dose (Given-NIC vs. Given-DENIC) with instructed nicotine dose expectancy (Told-NIC vs. Told-DENIC). Before and after smoking a study cigarette, smokers completed a vigilance task where they pressed buttons to every third consecutive even or odd digit, while ignoring intermittent smoking, pleasant, unpleasant, and neutral picture distracters. We examined the early posterior negativity (EPN) and late positive potential (LPP) components of the event-related potentials (ERPs) to the distracters, reaction time (RT) to the target digits, and ratings of the study cigarettes. The EPN was sensitive to both given and instructed nicotine dose, while the instructed dose moderated the impact of given dose for the LPP. The RT metrics were sensitive to given but not to instructed dose. The effects of given dose on ratings following cigarette smoking (e.g. enjoyment) were moderated by the instructed dose. The ERP findings suggest that the anticipated effects of nicotine improve attention much like receiving actual nicotine.

In this study, we examined the relationship between the level of daily cigarette consumption and the startle response to affective and cigarette-related cues among treatment-seeking smokers. Before receiving any behavioral or pharmacological treatment, 136 smokers attended a baseline laboratory session, during which we recorded their reflexive eyeblink responses to acoustic startle probes while they were viewing pleasant, unpleasant, neutral, and cigarette-related pictures. We found that 1) cigarette-related and pleasant pictures similarly reduced the startle magnitude compared to neutral pictures; 2) the magnitude of startle modulation rendered by pleasant or unpleasant pictures did not differ among light, moderate, and heavy smokers; and 3) startle attenuation by cigarette-related pictures was greater in heavy smokers than in light smokers. These results suggest that similar to pleasant stimuli, cigarette-related cues are motivationally salient for smokers, and that this salience increases with nicotine dependence.

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.

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 event-related potentials, 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.

The current study examined emotional reflex reactions of participants threatened with respiratory distress caused by imposing a resistive load at inspiration. Cues signaling threat (breathing MAY be difficult) and safe periods were intermixed while startle reflexes, heart rate, skin conductance, and facial EMG activity were measured. Compared to safe cues, threat cues elicited significant startle potentiation, enhanced skin conductance, heightened corrugator EMG changes, and pronounced "fear bradycardia" consistent with defensive activation in the context of threatened respiratory dysfunction. These data indicate that anticipating respiratory resistance activates defensive responding, which may mediate symptomatology in patients with panic and other anxiety disorders.

We used multimodal measurement to evaluate whether (a) nicotine dependence is associated with baseline and postquit negative affect and craving, (b) smoking relapse is associated with greater negative affect and craving than abstinence, and (c) craving is associated with negative affect. Treatment-seeking smokers were randomly assigned to either a brief behaviorally based smoking-cessation treatment condition or to a delayed treatment control condition. Participants in the treatment condition attended four assessment sessions, 4 –5 days prequit (baseline), 1–2 days postquit, 3–5 days postquit, and 10 –14 days postquit, while controls attended four sessions spaced over the same intervals. Retrospective questionnaires were collected at the beginning of each session, and corrugator EMG and in-session ratings were collected during viewing of affective and cigarette-related slides. The multimodal measures indicated that more dependent smokers experienced greater negative affect and craving at baseline and postquit, regardless of abstinence status. The self-report measures indicated that both relapsed and abstinent smokers reported greater negative affect and craving than control smokers. Craving was associated with negative affect across measurement modalities. These results highlight the benefits of using multimodal measures to study the impact of nicotine dependence and withdrawal on negative affect and craving.