Jennifer A. Minnix

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.

Can EEG asymmetry patterns predict future development of anxiety and depression? A preliminary study.

Previous research has shown that those reporting symptoms of depression and anxiety tend to exhibit greater relative right frontal electroencephalographic (EEG) activity. Thus, Davidson [Davidson, R.J., 1995. Cerebral asymmetry, emotion, and affective style. In: Davidson, R.J., Hugdahl, K. (Eds.), Brain Asymmetry. MIT, Cambridge, pp. 361-387] has suggested that greater relative right anterior activity may act as a vulnerability marker for the development of depression and anxiety disorders. This study therefore examined whether anterior and posterior EEG asymmetry patterns predicted anxiety and depressive symptoms one year later. At time 1, participants completed the Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI) and had baseline EEG activity recorded. Participants then completed the BDI and STAI one year later. Those with relatively greater EEG activity in the right anterior region reported greater trait anxiety one year later. These preliminary results suggest that relative right frontal EEG activity may predict future development of anxiety symptoms.

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.

Effects of an intensive depression-focused intervention for smoking cessation in pregnancy.

OBJECTIVE The objective of this study was to evaluate a depression-focused treatment for smoking cessation in pregnant women versus a time and contact health education control. We hypothesized that the depression-focused treatment would lead to improved abstinence and reduced depressive symptoms among women with high levels of depressive symptomatology. No significant main effects of treatment were hypothesized. METHOD Pregnant smokers (N = 257) were randomly assigned to a 10-week, intensive, depression-focused intervention (cognitive behavioral analysis system of psychotherapy; CBASP) or to a time and contact control focused on health and wellness (HW); both included equivalent amounts of behavioral and motivational smoking cessation counseling. Of the sample, 54% were African American, and 37% met criteria for major depression. Mean age was 25 years (SD = 5.9), and women averaged 19.5 weeks (SD = 8.5) gestation at study entry. We measured symptoms of depression using the Center for Epidemiological Studies-Depression Scale (Radloff, 1977). RESULTS At 6 months posttreatment, women with higher levels of baseline depressive symptoms treated with CBASP were abstinent significantly more often, F(1, 253) = 5.61, p = .02, and had less depression, F(1, 2620) = 10.49, p = .001, than those treated with HW; those with low baseline depression fared better in HW. Differences in abstinence were not retained at 6 months postpartum. CONCLUSIONS The results suggest that pregnant women with high levels of depressive symptoms may benefit from a depression-focused treatment in terms of improved abstinence and depressive symptoms, both of which could have a combined positive effect on maternal and child health.

Brain reactivity to emotional, neutral and cigarette-related stimuli in smokers

Addiction has been described as the pathological usurpation of the neural mechanisms normally involved in emotional processing. Event‐related potentials (ERPs) can provide a non‐invasive index of neural responses associated with the processing of emotionally relevant stimuli and serve as a tool for examining temporal and spatial commonalities between the processing of intrinsically motivating stimuli and drug cues. Before beginning a smoking cessation program, 116 smokers participated in a laboratory session in which dense‐array ERPs (129 sensors) were recorded during the presentation of pictures with emotional (pleasant and unpleasant), neutral and cigarette‐related content. ERP differences among categories were analyzed with use of randomization tests on time regions of interest identified by temporal principal component analysis. Both emotional and cigarette‐related pictures prompted significantly more positivity than did neutral pictures over central, parietal, and frontal sites in the 452–508 ms time window. During the 212–316 ms time window, both pleasant and cigarette‐related pictures prompted less positivity than neutral images did. Cigarette‐related pictures enhanced the amplitude of the P1 component (136–144 ms) above the levels measured in the emotional and neutral conditions. These results support the hypothesis that for smokers, cigarette‐related cues are motivationally relevant stimuli that capture attentional resources early during visual processing and engage brain circuits normally involved in the processing of intrinsically emotional stimuli.

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.

Relative left-frontal activity is associated with increased depression in high reassurance-seekers

Excessive reassurance-seeking, which has been associated with depression in many studies, can be defined as the relatively stable tendency to seek assurance perseveratively from others. We hypothesized that although depression has been associated with left-frontal EEG hypoactivity, reassurance-seekers may possess a unique diathesis that is more likely to be associated with increased left-frontal activity. Data were collected from 12 volunteers who were receiving therapeutic services from a University Clinic. EEG asymmetry scores were averaged over two measurement occasions at least 3 weeks apart. As predicted, stable relative right-frontal activity was associated with increased depression in those who were low on reassurance-seeking, while stable relative left-frontal activity was associated with increased depression among high reassurance-seekers. Perhaps those who seek reassurance excessively do so because of their inability to alter their behavior even when environmental cues are no longer reinforcing, which can maintain or exacerbate their depressive symptoms.

The DRD2 TaqI-B polymorphism and its relationship to smoking abstinence and withdrawal symptoms

The dopamine receptor D2 (DRD2) gene has polymorphisms that have been linked to regulation of the dopamine system and to an increased prevalence of smoking. The present study examined the relationship of the DRD2 TaqI-A and -B polymorphisms with short-term clinical outcome (abstinence and withdrawal symptoms), collected from daily (14 pre-quit and 42 post-quit) diary data among smokers (n=116) treated with the nicotine patch plus either venlafaxine or placebo. The results showed that B1/B1 or B1/B2 smokers were slightly less likely to be abstinent on a given day than those homozygous for the TaqI-B2 allele. Significant DRD2 TaqI-B × time interactions were found for several of the withdrawal scales, indicating that those smokers with the B1/B1 or B1/B2 genotypes tended to report more symptoms over time compared to those with the B2/B2 genotype. No interactions or main effects were found for the DRD2 TaqI-A polymorphism. The findings demonstrate that smokers homozygous for the TaqI-B2 allele experience progressive improvement in self-reported withdrawal symptoms while smokers with the TaqI-B1 allele showing little change.

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.

Cigarette cues capture smokers' attention: Evidence from event-related potentials

Abstract Before starting a smoking cessation treatment, 51 smokers took part in a study aimed at investigating brain mechanisms associated with attention allocation. Event-related potentials to acoustic startle probes were recorded from 129 sensors during the presentation of neutral, pleasant, unpleasant, and cigarette-related pictures. Results indicated that the amplitude of the startle probe P3 component was reduced for pleasant, unpleasant, and cigarette-related conditions relative to neutral. Surface Laplacian estimates showed that sources of electrocortical activity under frontal and parietal sensors contributed to the modulation of this effect. For smokers, cigarette-related stimuli, like intrinsically motivating ones, capture attentional resources and therefore reduce the ability to process competing stimuli. The depletion of attentional resources in the presence of cigarette-related cues may contribute to the high relapse rate observed during attempts to quit smoking.