Hippocampal and striatal gray matter volume are associated with a smoking cessation treatment outcome: results of an exploratory voxel-based morphometric analysis

Rationale  

Compared to nonsmokers, smokers exhibit a number of potentially important differences in regional brain structure including reduced gray matter (GM) volume and/or density in areas including frontal and cingulate cortices, thalamus, and insula. However, associations between brain structure and smoking cessation treatment outcomes have not been reported.     

Severity of nicotine dependence modulates cue-induced brain activity in regions involved in motor preparation and imagery

Rationale

In nicotine-dependent subjects, cues related to smoking elicit activity in brain regions linked to attention, memory, emotion and motivation. Cue-induced brain activation is associated with self-reported craving but further correlates are widely unknown.

Objectives

This study was conducted to investigate whether brain activity elicited by smoking cues increases with severity of nicotine dependence and intensity of cue-elicited craving.

Methods

Ten healthy male smokers whose degree of nicotine dependence ranged from absent to severe were investigated. Visual smoking cues and neutral stimuli were presented in a block design during functional magnetic resonance imaging (fMRI). Using multiple linear regression analysis, the blood oxygen level dependent (BOLD) response to smoking cues was correlated with severity of nicotine dependence assessed with the Fagerström Test of Nicotine Dependence (FTND) and with cue-induced craving.

Results

Significant positive correlations between the BOLD activity and FTND scores were found in brain areas related to visuospatial attention (anterior cingulate cortex, parietal cortex, parahippocampal gyrus and cuneus) and in regions involved in motor preparation and imagery (primary and premotor cortex, supplementary motor area). Intensity of cue-induced craving was significantly associated with greater BOLD activation in mesocorticolimbic areas engaged in incentive motivation and in brain regions related to episodic memory.

Conclusions

Our study suggests that severity of nicotine dependence and intensity of craving are independently associated with cue-induced brain activation in separate neuronal networks. The observed association between severity of dependence and brain activity in regions involved in allocation of attention, motor preparation and imagery might reflect preparation of automated drug taking behavior thereby facilitating cue-induced relapse.     

Prefrontal and limbic resting state brain network functional connectivity differs between nicotine-dependent smokers and non-smoking controls

Background

Brain dysfunction in prefrontal cortex (PFC) and dorsal striatum (DS) contributes to habitual drug use. These regions are constituents of brain networks thought to be involved in drug addiction. To investigate whether networks containing these regions differ between nicotine dependent female smokers and age-matched female non-smokers, we employed functional MRI (fMRI) at rest.

Methods

Data were processed with independent component analysis (ICA) to identify resting state networks (RSNs). We identified a subcortical limbic network and three discrete PFC networks: a medial prefrontal cortex (mPFC) network and right and left lateralized fronto-parietal networks common to all subjects. We then compared these RSNs between smokers and non-smokers using a dual regression approach.

Results

Smokers had greater coupling versus non-smokers between left fronto-parietal and mPFC networks. Smokers with the greatest mPFC–left fronto-parietal coupling had the most DS smoking cue reactivity as measured during an fMRI smoking cue reactivity paradigm. This may be important because the DS plays a critical role in maintaining drug-cue associations. Furthermore, subcortical limbic network amplitude was greater in smokers.

Conclusions

Our results suggest that prefrontal brain networks are more strongly coupled in smokers, which could facilitate drug-cue responding. Our data also are the first to document greater reward-related network fMRI amplitude in smokers. Our findings suggest that resting state PFC network interactions and limbic network amplitude can differentiate nicotine-dependent smokers from controls, and may serve as biomarkers for nicotine dependence severity and treatment efficacy.     

Greater risk sensitivity of dorsolateral prefrontal cortex in young smokers than in nonsmokers

Rationale

Despite a national reduction in the prevalence of cigarette smoking, ~19 % of the adult US population persists in this behavior, with the highest prevalence among 18–25-year-olds. Given that the choice to smoke imposes a known health risk, clarification of brain function related to decision-making, particularly involving risk-taking, in smokers may inform prevention and smoking cessation strategies.

Objectives

This study aimed to compare brain function related to decision-making in young smokers and nonsmokers.

Methods

The Balloon Analogue Risk Task (BART) is a computerized risky decision-making task in which participants pump virtual balloons, each pump associated with an incremental increase in potential payoff on a given trial but also with greater risk of balloon explosion and loss of payoff. We used this task to compare brain activation associated with risky decision-making in smokers (n?=?18) and nonsmokers (n?=?25), while they performed the BART during functional magnetic resonance imaging (fMRI). The participants were young men and women, 17–21 years of age.

Results

Risk level (number of pumps) modulated brain activation in the right dorsolateral and ventrolateral prefrontal cortices more in smokers than in nonsmokers, and smoking severity (Heaviness of Smoking Index) was positively related to this modulation in an adjacent frontal region.

Conclusions

Given evidence for involvement of the right dorsolateral and ventrolateral prefrontal cortices in inhibitory control, these findings suggest that young smokers have a different contribution of prefrontal cortical substrates to risky decision-making than nonsmokers. Future studies are warranted to determine whether the observed neurobiological differences precede or result from smoking.     

Thalamic glutamate decreases with cigarette smoking

Rationale

Findings from animal studies and human PET imaging indicate that nicotine and cigarette smoking affect glutamate (Glu) and related neurochemical markers in the brain and imply that smoking reduces extracellular Glu. As Glu release is mediated by nicotinic acetylcholine receptors (nAChRs), which are present at high concentrations in the thalamus, we examined the effects of smoking on thalamic Glu.

Objective

To determine the effects of tobacco smoking on thalamic glutamate levels.

Methods

Thalamic Glu levels were measured in vivo in 18 smokers and 16 nonsmokers using proton magnetic resonance spectroscopic imaging (¹H MRSI) at 1.5 T.

Results

Mean Glu levels did not differ significantly between the subject groups. However, within smokers, Glu levels were negatively correlated with self-reports of both cigarettes/day over the last 30 days (r?=??0.64, p?=?0.006) and pack-years of smoking (r?=??0.66, p?=?0.005).

Conclusions

Consistent with expectations based on preclinical studies, within smokers, cigarettes/day and pack-years are associated with reduced Glu in thalamus, a brain region rich in nAchRs. These results encourage work on candidate glutamatergic therapies for smoking cessation and suggest a noninvasive metric for their action in the brain.     

The effect of nicotine and trauma context on acoustic startle in smokers with and without posttraumatic stress disorder

Rationale  

Exaggerated startle response is a prominent feature of posttraumatic stress disorder (PTSD) although results examining differences in the acoustic startle response (ASR) between those with and without PTSD are mixed. One variable that may affect ASR among persons with PTSD is smoking. Individuals with PTSD are more likely to smoke and have greater difficulty quitting smoking. While smokers with PTSD report that smoking provides significant relief of negative affect and PTSD symptoms, the effects of smoking or nicotine deprivation on startle reactivity among smokers with PTSD are unknown.     

Worth the wait: effects of age of onset of marijuana use on white matter and impulsivity

Rationale

Marijuana (MJ) use continues to rise, and as the perceived risk of using MJ approaches an all-time historic low, initiation of MJ use is occurring at even younger ages. As adolescence is a critical period of neuromaturation, teens and emerging adults are at greater risk for experiencing the negative effects of MJ on the brain. In particular, MJ use has been shown to be associated with alterations in frontal white matter microstructure, which may be related to reports of increased levels of impulsivity in this population.

Objectives

The aim of this study was to examine the relationship between age of onset of MJ use, white matter microstructure, and reported impulsivity in chronic, heavy MJ smokers.

Methods

Twenty-five MJ smokers and 18 healthy controls underwent diffusion tensor imaging and completed the Barratt Impulsiveness Scale. MJ smokers were also divided into early onset (regular use prior to age 16) and late onset (age 16 or later) groups in order to clarify the impact of age of onset of MJ use on these variables.

Results

MJ smokers exhibited significantly reduced fractional anisotropy (FA) relative to controls, as well as higher levels of impulsivity. Earlier MJ onset was also associated with lower levels of FA. Interestingly, within the early onset group, higher impulsivity scores were correlated with lower FA, a relationship that was not observed in the late onset smokers.

Conclusions

MJ use is associated with white matter development and reported impulsivity, particularly in early onset smokers.     

Neural substrates of acupuncture in the modulation of cravings induced by smoking-related visual cues: an FMRI study

Rationale

Cue reactivity is a key factor in modulating motivational and goal-directed behaviors associated with compulsive drug intake and relapse. Smoking-associated cues produce smoking urges and cravings and are accompanied by the activation of brain regions involved in attention, motivation, and reward.

Objectives

We investigated whether acupuncture ameliorates cravings induced by smoking-related visual cues, and we explored the neural mechanisms underlying the effects of acupuncture on modulating smoking urges.

Methods

After 36 h of smoking abstinence, 25 right-handed male smokers underwent fMRI, during which smoking-related and neutral visual cues were presented. Twelve subjects were treated with real acupuncture (RA) at HT7 and 13 subjects received sham acupuncture (SA). During the scanning sessions, craving scores to smoking-related visual cues were assessed before and after RA or SA treatment. The differences in brain responses to smoking vs. neutral cues after treatment between the RA and SA groups were detected using three-way ANOVAs (Cue × Session × Group).

Results

After treatment, the craving scores were significantly decreased in the RA group, as compared to the SA group. When we explored the neural substrates of acupuncture on the modulation of cravings induced by smoking cues, significant differences were found in the medial prefrontal cortex, the premotor cortex, the amygdala, the hippocampus, and the thalamus.

Conclusions

These findings suggest that acupuncture alleviates cue-induced cravings through the regulation of activity in brain regions involved in attention, motivation, and reward relative to craving scores in the initial abstinence phase.     

Association of abstinence-induced alterations in working memory function and COMT genotype in smokers

Rationale

The common methionine (met) for valine (val) at codon 158 (val¹⁵⁸met) polymorphism in the catechol-O-methyltransferase (COMT) gene has been associated with nicotine dependence, alterations in executive cognitive function, and abstinence-induced working memory deficits in smokers.

Objectives

We sought to replicate the association of the COMT val allele with abstinence-induced alterations in working memory-related activity in task-positive (executive control) and task-negative (default mode network) regions.

Methods

Forty smokers (20 val/val and 20 met/met) performed an N-back task while undergoing blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) on two separate occasions: following 72 h of confirmed abstinence and during smoking as usual. An independent sample of 48 smokers who completed the identical N-back task during fMRI in smoking vs. abstinence for another study was used as a validation sample.

Results

Contrary to expectations, genotype by session interactions on BOLD signal in executive control regions (dorsolateral prefrontal cortex and dorsal cingulate/medial prefrontal cortex) revealed significant abstinence-induced reductions in the met/met group, but not the val/val group. Results also revealed that val/val smokers may exhibit less suppression of activation in task-negative regions such as the posterior cingulate cortex during abstinence (vs. smoking). These patterns were confirmed in the validation sample and in the whole-brain analysis, though the regions differed from the a priori regions of interest (ROIs) (e.g., precuneus, insula).

Conclusions

The COMT val¹⁵⁸met polymorphism was associated with abstinence-related working memory deficits in two independent samples of smokers. However, inconsistencies compared to prior findings and across methods (ROI vs. whole-brain analysis) highlight the challenges inherent in reproducing results of imaging genetic studies in addiction.     

Differences in negative mood-induced smoking reinforcement due to distress tolerance, anxiety sensitivity, and depression history

Rationale  

Negative mood increases smoking reinforcement and may do so to a greater degree in smokers vulnerable to negative mood dysregulation.     

Sensory modality of smoking cues modulates neural cue reactivity

Rationale

Behavioral experiments have demonstrated that the sensory modality of presentation modulates drug cue reactivity.

Objectives

The present study on nicotine addiction tested whether neural responses to smoking cues are modulated by the sensory modality of stimulus presentation.

Methods

We measured brain activation using functional magnetic resonance imaging (fMRI) in 15 smokers and 15 nonsmokers while they viewed images of smoking paraphernalia and control objects and while they touched the same objects without seeing them.

Results

Haptically presented, smoking-related stimuli induced more pronounced neural cue reactivity than visual cues in the left dorsal striatum in smokers compared to nonsmokers. The severity of nicotine dependence correlated positively with the preference for haptically explored smoking cues in the left inferior parietal lobule/somatosensory cortex, right fusiform gyrus/inferior temporal cortex/cerebellum, hippocampus/parahippocampal gyrus, posterior cingulate cortex, and supplementary motor area.

Conclusions

These observations are in line with the hypothesized role of the dorsal striatum for the expression of drug habits and the well-established concept of drug-related automatized schemata, since haptic perception is more closely linked to the corresponding object-specific action pattern than visual perception. Moreover, our findings demonstrate that with the growing severity of nicotine dependence, brain regions involved in object perception, memory, self-processing, and motor control exhibit an increasing preference for haptic over visual smoking cues. This difference was not found for control stimuli. Considering the sensory modality of the presented cues could serve to develop more reliable fMRI-specific biomarkers, more ecologically valid experimental designs, and more effective cue-exposure therapies of addiction.     

A randomised placebo-controlled trial of oral hydrocortisone for treating tobacco withdrawal symptoms

Rationale  

Many smokers experience a decline in cortisol to sub-normal levels during the first days of smoking cessation. A greater decline in cortisol is associated with more intense cigarette withdrawal symptoms, urge to smoke and relapse to smoking. Findings from an uncontrolled study suggest that glucocorticoids could ameliorate cigarette withdrawal.     

Automatic approach bias towards smoking cues is present in smokers but not in ex-smokers

Rationale

Drug-addicted individuals show automatic approach tendencies towards drug-related cues, i.e., an approach bias (ApB). Nevertheless, little is known about ApB in tobacco smokers and about the presence of ApB after smoking abstinence.

Objectives

We investigated ApB to smoking cues in heavy tobacco smokers versus never-smokers and studied its relation to smoking characteristics and craving. Second, we compared ApBs of heavy smokers with biases of abstinent heavy smokers.

Method

A group of current heavy smokers (n?=?24), ex-smokers who were abstinent for at least 5 years (n?=?20), and never-smokers (n?=?20) took part in the experiment. An indirect smoking approach avoidance task was performed, in which participants were required to respond to pictures of smoking and neutral cues by pulling (approach) or pushing (avoid) on a joystick, according to the content-irrelevant format of the picture (landscape or portrait). Craving scores were examined using the Questionnaire of Smoking Urges.

Results

Heavy smokers showed an ApB for smoking cues compared to ex-smokers and never-smokers, which correlated positively to craving scores. There were no group differences in ApB scores for ex-smokers and never-smokers.

Conclusion

These results suggest that ApBs for smoking cues are present in heavy smokers and decrease after long-term successful smoking cessation.     

A preliminary investigation of varenicline for heavy drinking smokers

Rationale  

Varenicline, an approved smoking cessation pharmacotherapy, also shows promise as a potential treatment for alcohol dependence. However, varenicline has not been tested in heavy drinkers, and it remains to be determined whether varenicline could reduce alcohol craving and consumption in smokers who are trying to quit smoking.     

Nicotine withdrawal modulates frontal brain function during an affective Stroop task

Background  

Among nicotine-dependent smokers, smoking abstinence disrupts multiple cognitive and affective processes including conflict resolution and emotional information processing (EIP). However, the neurobiological basis of abstinence effects on resolving emotional interference on cognition remains largely uncharacterized. In this study, functional magnetic resonance imaging (fMRI) was used to investigate smoking abstinence effects on emotion–cognition interactions.     

Does the exposure to smoking cues in movies affect adolescents' immediate smoking behavior?

Introduction

Various studies have demonstrated that environmental smoking cues elicit smoking-related responses in smokers. However, cue reactivity studies among adolescent smokers are scarce. Therefore, the aim of this study was to examine the effect of smoking portrayal in movies on immediate smoking behavior in adolescent smokers.

Method

A total of 65 adolescent daily smokers (between the ages of 16 and 18 years) were exposed to a one-hour movie clip, with or without smoking characters, and were allowed to smoke while watching the movie.

Results

The exposure to smoking cues in movies had no effect on immediate smoking behavior. This association was not affected by several smoking- and movie-related variables.

Conclusions

No influence of smoking cues in movies on immediate smoking behavior in adolescent daily smokers was found. More experimental research on the effects of environmental cues on adolescent smokers in different stages of addiction is needed.     

Alcohol expectancy increases positive responses to cigarettes in young, escalating smokers

Rationale  

A large proportion of smokers consolidate their smoking patterns during young adulthood, and it is possible that the high rates of drinking found in this age group may facilitate the transition from nondaily to daily cigarette use.     

Socio-demographic and clinical characteristics of heavy and non-heavy smokers among schizophrenia inpatients in a Chinese Han population

Objective

Despite higher smoking rates in schizophrenia, few studies have explored the clinical–demographic correlates of different amounts of smoking exposure. Little is known about the association between smoking severity and clinical phenotypes in Chinese patients with schizophrenia.

Materials and methods

We investigated differences between heavy (≥1 pack/day) and non-heavy (<1 pack/day) smoking in 550 male inpatients with schizophrenia using clinician-administered questionnaires and the Fagerstrom Test for Nicotine Dependence. They also were rated on the Positive and Negative Symptom Scale (PANSS), the Simpson and Angus Extrapyramidal Symptom Rating Scale (SAES), and the Abnormal Involuntary Movement Scale (AIMS), as well as were assayed with laboratory tests and an electrocardiogram.

Results

Heavy smoking prevalence was approximately 31 %. Compared to the non-heavy smokers, the heavy smokers were younger, more with paranoid subtype but less with disorganized subtype schizophrenia, smoked at an earlier age, fewer getting clozapine or all atypical antipsychotics together, and were taking larger doses of antipsychotic drugs. The heavy smokers scored significantly lower on the PANSS negative symptom subscore and total score, and also on the SAES and AIMS scores than the non-heavy smokers. In addition, heavy smokers displayed longer rate-corrected electrocardiographic QT intervals, but without any significant differences in other laboratory tests.

Conclusion

Our results suggest several clinical or demographic differences between the heavy and non-heavy smoking patients with schizophrenia in a Chinese population. Heavy smoking remains a general health risk for schizophrenia.     

Nicotine dependence and serum BDNF levels in male patients with schizophrenia

Objective  

Schizophrenia is associated with a significantly high prevalence of smoking. Upregulation of neurotrophins by nicotine is well established. Accumulating evidence shows that brain-derived neurotrophic factor (BDNF) may be involved in the pathophysiology of schizophrenia. The purposes of this study were to compare BDNF levels in smokers to nonsmokers with schizophrenia and examine the association between BDNF levels and psychopathological symptoms.