Stephen J. Wilson

Prefrontal responses to drug cues: a neurocognitive analysis

The construct of craving has been central to addiction research for more than 50 years. Only recently have investigators begun to apply functional neuroimaging techniques to the study of drug cue reactivity, and a small but growing number of studies implicate a distributed system of brain regions in the pathogenesis of craving. The internal consistency of this burgeoning literature has thus far been disappointing, however, leaving open the question of which brain regions contribute to craving. Here we review neuroimaging studies of cue-elicited craving in the context of a framework drawn from behavioral research indicating that perceived drug use opportunity significantly affects responses to the presentation of drug cues. Using this framework provides a way to reconcile discrepant findings among brain-imaging studies of cue-elicited craving.

Instructed smoking expectancy modulates cue-elicited neural activity: A preliminary study

In recent years, research applying functional neuroimaging to the study of cue-elicited drug craving has emerged. This research has begun to identify a distributed system of brain activity during drug craving. A review of this literature suggested that expectations regarding the opportunity to use a drug affected the pattern of neural responses elicited by drug cues. Using functional magnetic resonance imaging (fMRI), we examined the effects of smoking expectancy on the neural response to neutral (e.g., roll of tape) and smoking-related (a cigarette) stimuli in male cigarette smokers deprived of nicotine for 8 hr. As predicted, several brain regions (e.g., the anterior cingulate cortex) exhibited differential activation during cigarette versus neutral cue exposure. Moreover, we found that subregions of the prefrontal cortex (i.e., ventromedial, ventrolateral, and dorsolateral prefrontal cortices) showed cue-elicited activation that was modulated by smoking expectancy. These results highlight the importance of perceived drug use opportunity in the neurobiological response to drug cues.

Development of a questionnaire for assessing dependence on electronic cigarettes among a large sample of ex-smoking E-cigarette users.

INTRODUCTION Electronic cigarettes (e-cigs) are becoming increasingly popular, but little is known about their dependence potential. This study aimed to assess ratings of dependence on electronic cigarettes and retrospectively compare them with rated dependence on tobacco cigarettes among a large sample of ex-smokers who switched to e-cigs. METHODS A total of 3,609 current users of e-cigs who were ex-cigarette smokers completed a 158-item online survey about their e-cig use, including 10 items designed to assess their previous dependence on cigarettes and 10 almost identical items, worded to assess their current dependence on e-cigs (range 0-20). RESULTS Scores on the 10-item Penn State (PS) Cigarette Dependence Index were significantly higher than on the comparable PS Electronic Cigarette Dependence Index (14.5 vs. 8.1, p < .0001). In multivariate analysis, those who had used e-cigs longer had higher e-cig dependence scores, as did those using more advanced e-cigs that were larger than a cigarette and had a manual button. Those using zero nicotine liquid had significantly lower e-cig dependence scores than those using 1-12 mg/ml, who scored significantly lower than those using 13 or greater mg/ml nicotine liquid (p < .003). CONCLUSIONS Current e-cigarette users reported being less dependent on e-cigarettes than they retrospectively reported having been dependent on cigarettes prior to switching. E-cig dependence appears to vary by product characteristics and liquid nicotine concentration, and it may increase over time.

Adolescent brain maturation and smoking: what we know and where we're headed.

Smoking is a leading cause of mortality and morbidity worldwide. Smoking initiation often occurs during adolescence. This paper reviews and synthesizes adolescent development and nicotine dependence literatures to provide an account of adolescent smoking from onset to compulsive use. We extend neurobiological models of adolescent risk-taking, that focus on the interplay between incentive processing and cognitive control brain systems, through incorporating psychosocial and contextual factors specific to smoking, to suggest that adolescents are more vulnerable than adults to cigarette use generally, but that individual differences exist placing some adolescents at increased risk for smoking. Upon smoking, adolescents are more likely to continue smoking due to the increased positive effects induced by nicotine during this period. Continued use during adolescence, may be best understood as reflecting drug-related changes to neural systems underlying incentive processing and cognitive control, resulting in decision-making that is biased towards continued smoking. Persistent changes following nicotine exposure that may underlie continued dependence are described. We highlight ways that interventions may benefit from a consideration of cognitive-neuroscience findings.

Quitting-unmotivated and quitting-motivated cigarette smokers exhibit different patterns of cue-elicited brain activation when anticipating an opportunity to smoke.

The authors examined the effects of smoking expectancy on cue-reactivity among those motivated and those unmotivated to quit smoking using functional MRI. Cue-elicited activation was observed in the rostral prefrontal cortex (PFC) in smokers who expected to smoke within seconds, but not in those who expected to have to wait hours before having the chance to smoke, regardless of quitting motivation. For quitting-unmotivated smokers expecting to smoke, rostral PFC activation was strongly positively correlated with the activation of several areas previously linked to cue-reactivity, including the medial orbitofrontal cortex (OFC) and rostral anterior cingulate cortex (ACC). In contrast, there was a nonsignificant negative relationship between activation of the rostral PFC and activation of the medial OFC/rostral ACC in quitting-motivated smokers expecting to smoke. Results extend previous work examining the effects of smoking expectancy and highlight the utility of examining interregional covariation during cue exposure. Findings also suggest that investigators may need to pay close attention to the motivational contexts associated with their experiments when studying cue-reactivity, as these contexts can modulate not only responses to drug cues, but perhaps also the functional implications of observed activity.

Social perception of male and female computer synthesized speech

The present study addressed the issue of whether social perception of human speech and computerized text-to-speech (TTS) is affected by gender of voice and gender of listener. Listeners were presented with a persuasive argument in either male or female human or synthetic voice and were assessed on attitude change and their ratings of various speech qualities. The results indicated that female human speech was rated as preferable to female synthetic speech, and that male synthetic speech was rated as preferable to female synthetic speech. Degree of persuasion did not differ across human and synthetic speech, however, female listeners were persuaded more by the argument than male listeners were. Patterns of ratings across male and female listeners were fairly similar across human and synthetic speech, suggesting that gender stereotyping for human voices and computerized voices may occur in a similar fashion.

The persuasiveness of synthetic speech versus human speech

Is computer-synthesized speech as persuasive as the human voice when presenting an argument? After completing an attitude pretest, 193 participants were randomly assigned to listen to a persuasive appeal under three conditions: a high-quality synthesized speech system (DECtalk Express), a low-quality synthesized speech system (Monologue), and a tape recording of a human voice. Following the appeal, participants completed a posttest attitude survey and a series of questionnaires designed to assess perceptions of speech qualities, perceptions of the speaker, and perceptions of the message. The human voice was generally perceived more favorably than the computer-synthesized voice, and the speaker was perceived more favorably when the voice was a human voice than when it was computer synthesized. There was, however, no evidence that computerized speech, as compared with the human voice, affected persuasion or perceptions of the message. Actual or potential applications of this research include issues that should be considered when designing synthetic speech systems.

Effect of smoking opportunity on responses to monetary gain and loss in the caudate nucleus.

The authors examined the effects of smoking opportunity on neural responses to monetary outcomes in nicotine-deprived cigarette smokers. Participants who were told that they would be able to smoke during the study exhibited smaller responses to monetary gains and losses in the caudate nucleus than did those who anticipated having to wait several hours before having the opportunity to smoke. These findings highlight the importance of investigating the effects of perceived drug use opportunity on motivational processing in addicted populations.

Neuroimaging craving: urge intensity matters

Functional neuroimaging has become an increasingly common tool for studying drug craving. Furthermore, functional neuroimaging studies, which have addressed an incredibly diverse array of questions regarding the nature and treatment of craving, have had a substantial impact on theoretical models of addiction. Here, we offer three points related to this sizeable and influential body of research. First, we assert that the craving most investigators seek to study represents not just a desire but a strong desire to use drugs, consistent with prominent theoretical and clinical descriptions of craving. Secondly, we highlight that, despite the clear conceptual and clinical emphasis on craving as an intense desire, brain imaging studies often have been designed explicitly in a way that reduces the ability to generate powerful cravings. We illustrate this point by reviewing the peak urge levels endorsed by participants in functional magnetic resonance imaging (fMRI) studies of cigarette craving in nicotine-deprived versus non-deprived smokers. Thirdly, we suggest that brain responses measured during mild states of desire (such as following satiety) differ in fundamental ways from those measured during states of overpowering desire (i.e. craving) to use drugs. We support this position by way of a meta-analysis revealing that fMRI cue exposure studies using nicotine-deprived smokers have produced different patterns of brain activation to those using non-deprived smokers. Regarding brain imaging studies of craving, intensity of the urges matter, and more explicit attention to urge intensity in future work has the potential to yield valuable information about the nature of craving.

Weak ventral striatal responses to monetary outcomes predict an unwillingness to resist cigarette smoking

As a group, cigarette smokers exhibit blunted subjective, behavioral, and neurobiological responses to nondrug incentives and rewards, relative to nonsmokers. Findings from recent studies suggest, however, that there are large individual differences in the devaluation of nondrug rewards among smokers. Moreover, this variability appears to have significant clinical implications, since reduced sensitivity to nondrug rewards is associated with poorer smoking cessation outcomes. Currently, little is known about the neurobiological mechanisms that underlie these individual differences in the responsiveness to nondrug rewards. Here, we tested the hypothesis that individual variability in reward devaluation among smokers is linked to the functioning of the striatum. Specifically, functional magnetic resonance imaging was used to examine variability in the neural response to monetary outcomes in nicotine-deprived smokers anticipating an opportunity to smoke—circumstances found to heighten the devaluation of nondrug rewards by smokers in prior work. We also investigated whether individual differences in reward-related brain activity in those expecting to have access to cigarettes were associated with the degree to which the same individuals subsequently were willing to resist smoking in order to earn additional money. Our key finding was that deprived smokers who exhibited the weakest response to rewards (i.e., monetary gains) in the ventral striatum were least willing to refrain from smoking for monetary reinforcement. These results provide evidence that outcome-related signals in the ventral striatum serve as a marker for clinically meaningful individual differences in reward-motivated behavior among nicotine-deprived smokers.