Michael A. Sayette - US grants

The primary purposes of this FIRST application are: (a) to test mechanisms of alcohol's effects on social anxiety in men and women within the framework of the appraisal-disruption model, and (b) to determine whether there is an association among risk for alcoholism, sensitivity to the disruption of cognitive appraisal processes, and stress response dampening effects of alcohol. Subjects at high and low risk for alcoholism, based on family history of the disorder, will consume an alcoholic (.8 g/kg alcohol men;.7 g/kg women) or a placebo beverage, either before or after receiving stressful information. Subjects will be tested for cognitive deficits in both attentive (limited-capacity) and automatic processing. Stress response dampening (SRD) will be assessed using a multidimensional approach comprising subjective, psychophysiological, and behavior- expressive response systems. It is predicted that SRD effects of alcohol will be strongest when intoxication precedes the presentation of stressful information. Anxiolytic effects are predicted to correlate positively with disruption of cognitive appraisal processes. Specifically, alcohol is expected to disrupt the appraisal of new information by constraining the spread of activation to associated information in long-term memory. Moreover, subjects with a parental history of alcoholism are predicted to have greater cognitive impairment and stronger stress response dampening than subjects without such a family history. Investigation of both automatic and attentive cognitive processes will further understanding of the effects of alcohol on cognition per se. Identifying the relationship between disruption of cognitive processing and stress response dampening will elucidate the mechanisms contributing to the reinforcing effects of alcohol, and will help to integrate a large and inconsistent literature on alcohol-stress interactions. This research will advance knowledge of individual differences in the stress response dampening effects of alcohol, and will significantly increase understanding of the determinants of drinking patterns and alcohol abuse.

DESCRIPTION (provided by applicant): Smoking remains a leading preventable cause of mortality and morbidity. While it is relatively easy to develop nicotine dependence, it remains difficult to quit. Craving has been linked to nicotine dependence and the purpose of this competing renewal is to improve understanding of emotional and cognitive processes related to craving that underlie addiction. Because most lab-based craving studies involve subjects who do not expect to use the drug, the emotion experienced during such cravings tends to be negative. Outside the lab, however, cravings occur in conjunction with a variety of expectations regarding drug use, and in some cases are associated with positive anticipatory emotional states. A premise of the proposed study is that the loss of these positive anticipatory cravings after quitting constitutes a major challenge to remaining abstinent. The proposed laboratory research will apply theory and methods from experimental psychology to examine situational and individual difference factors that moderate the diverse effects of craving on affect and cognition, with particular emphasis on these positive craving states. The proposed study (n=300) will test the impact of treatment-seeking status (active vs. quitting smokers) and perceived smoking opportunity on a novel set of craving-related responses derived from basic research in emotion and cognitive science. To induce craving, abstinent smokers will be exposed to smoking cues, and instructions related to smoking opportunity will be manipulated. We also aim to evaluate the moderating effect of individual differences in personality, anhedonia, working memory, and dopamine-regulating gene variation on cravings. In addition, the proposed study will provide the first test to determine whether facial reactivity to smoking cues (coded using the Facial Action Coding System), can uniquely predict smoking relapse over an 8-week period following quitting. If successful, this test would offer early identification of those at high risk for relapse and suggest new directions for targeting affective processes in treatment. By tying craving to responses that are meaningfully linked to smoking, and that vary in different contexts and across individuals, the project aims to identify distinct craving patterns that may contribute to relapse risk. Irrespective of the outcome, the study will provide critical data regarding observable effects of an important but understudied form of anticipatory craving linked to positive affect, which will improve understanding of factors contributing to the etiology of nicotine addiction. In addition, identification of different emotional and cognitive experiences associated with positive cravings may lead to new directions for treatment that address the anhedonia and dysphoria smokers experience specifically as a result of losing these positive anticipatory experiences. PUBLIC HEALTH RELEVANCE: Craving is a cardinal feature of smoking addiction, which remains the leading cause of preventable mortality in the US. Despite its importance, research has relatively ignored the positive affect-related cravings often experienced by smokers while anticipating the smoking of their next cigarette. Understanding positive cravings, determining who is most sensitive to experiencing them, and examining the degree to which facial coding of these craving experiences can predict subsequent relapse, will advance knowledge regarding the emotional mechanisms underlying relapse and will suggest new directions for treatment that address the anhedonia and dysphoria smokers experience specifically as a result of losing these positive anticipatory experiences.

DESCRIPTION (provided by applicant): Social factors play a major role in alcohol use and dependence, but researchers rarely study the effects of alcohol in group settings. This project will systematically measure the effects of alcohol on positive and negative affect and social bonding during initial group formation, and determine if persons with personality traits posing a risk for alcoholism are more sensitive to these effects. Presumably, if such persons find effects of alcohol to be more rewarding, they will become more likely to rely on alcohol to regulate affect. Many of these traits are inherently social (e.g., extroversion), and this will be the first study to test their impact on the effects of alcohol in a social setting. Seven-hundred-twenty social drinkers will be assembled into 240 three-person groups of strangers (all female groups, groups with one male and two females, groups with two males and one female, and all male groups). All members of each group will drink over 30-min a moderate dose of alcohol (males: 0.82 g/kg;females: 0.74 g/kg), a placebo, or a nonalcoholic control drink. This group drinking period will be recorded using a digital control system that synchronizes multiple streams of video as interactions unfold over time. This system enables precise analysis of the duration and sequence of selected facial expressions and speech behaviors. The project will be informed by (a) social psychological theory and research on small groups, (b) advances in the systematic measurement of observed behavior, and (c) multi-level statistical modeling techniques that account for the nonindependence of group members. We will assess a variety of individual-level responses, including facial expressions related to positive and negative affect using Ekman et al's (2002) Facial Action Coding System. We also will assess a range of group-level responses, including coordination of smiling and speech behaviors. We predict that the belief that one has consumed alcohol will enhance positive affect, reduce negative affect (e.g., social anxiety), and facilitate social bonding during initial group formation (i.e., a placebo effect). Further, we predict that actual alcohol consumption will enhance social bonding processes beyond what is found with a placebo beverage. This study will be the first with sufficient power to comprehensively examine the moderating roles of gender and personality traits on the reinforcing effects of alcohol in groups. Regardless of the outcome, the study will provide critical data regarding observable effects of alcohol on social drinkers that will help illuminate the social and emotional determinants of drinking patterns and problems for men and women.

DESCRIPTION (provided by applicant): Cigarette craving is a vital feature of smoking, which is the leading preventable cause of cancer. While smokers generally recognize this danger, during hot moments of temptation the appeal of smoking a cigarette rises, previously learned coping skills or quit-smoking messages may be either ignored or abandoned, and often the smoking habit persists. Despite its importance, research has struggled to develop effective treatments for craving relief and new innovative approaches are sorely needed. The proposed project addresses RFA-CA- 12-015: Research Answers to NCI's Provocative Questions (PQA3) by evaluating a novel bio-behavioral approach to help smokers reduce their cigarette cravings. Integrating basic theory and research derived from three disciplines that rarely have been applied to smoking research (olfaction, emotion, and cognition), the proposed project aims to test the effectiveness of specific olfactory cues to reduce cigarette cravings. In addition - and pertinent to the RFA - this research tests a range of individual difference factors such as working memory, personality, motivation to quit, and gender, which prior theory and research suggest should moderate the craving-reducing effects of olfactory cues. As a consequence, the project will advance knowledge of why certain individuals may have particular trouble managing their cravings and refraining from smoking. Abstinent smokers (N=250) with varying motivations to quit will attend a multi-session experiment. Initially participants will sample and rate a serie of olfactory cues on several dimensions, including pleasantness, familiarity, and associated memories. Participants then will be exposed to in vivo smoking cues, which in the context of smoking abstinence, produce robust cigarette cravings. While at peak craving, they will be randomly assigned to sniff an odor that they had previously rated as either being most pleasant (and unrelated to smoking), a tobacco odor, or a neutral odor while urge, mood, and a novel set of craving-related responses derived from basic research in cognition and emotion (including Paul Ekman's Facial Action Coding System) will be assessed. This research also will test key mechanisms of craving relief that relate to existing theories of craving and addiction. In addition the project will monitor the durability of this predicted odor- induced craving-relief within a sinle experimental session and across sessions conducted on different days. This conceptually-driven research is motivated by neurobiological and behavioral research indicating the unique power of olfaction to trigger emotional memories and to fundamentally alter emotional states such as craving. The proposed project will examine interactions between emotional and cognitive processes that, while craving, may serve to hamper effective coping, and will set the stage for future research testing the impact of olfaction - alone or combined with other agents (e.g., nicotine patches) - on smoking cessation. Irrespective of the outcome, the proposed research using a novel set of measures will provide critical data regarding the interaction of emotional and cognitive processes during craving.

DESCRIPTION (provided by applicant): Cigarette craving is a vital feature of smoking, which is the leading preventable cause of cancer. While smokers generally recognize this danger, during hot moments of temptation the appeal of smoking a cigarette rises, previously learned coping skills or quit-smoking messages may be either ignored or abandoned, and often the smoking habit persists. Despite its importance, research has struggled to develop effective treatments for craving relief and new innovative approaches are sorely needed. The proposed project addresses RFA-CA- 12-015: Research Answers to NCI's Provocative Questions (PQA3) by evaluating a novel bio-behavioral approach to help smokers reduce their cigarette cravings. Integrating basic theory and research derived from three disciplines that rarely have been applied to smoking research (olfaction, emotion, and cognition), the proposed project aims to test the effectiveness of specific olfactory cues to reduce cigarette cravings. In addition - and pertinent to the RFA - this research tests a range of individual difference factors such as working memory, personality, motivation to quit, and gender, which prior theory and research suggest should moderate the craving-reducing effects of olfactory cues. As a consequence, the project will advance knowledge of why certain individuals may have particular trouble managing their cravings and refraining from smoking. Abstinent smokers (N=250) with varying motivations to quit will attend a multi-session experiment. Initially participants will sample and rate a serie of olfactory cues on several dimensions, including pleasantness, familiarity, and associated memories. Participants then will be exposed to in vivo smoking cues, which in the context of smoking abstinence, produce robust cigarette cravings. While at peak craving, they will be randomly assigned to sniff an odor that they had previously rated as either being most pleasant (and unrelated to smoking), a tobacco odor, or a neutral odor while urge, mood, and a novel set of craving-related responses derived from basic research in cognition and emotion (including Paul Ekman's Facial Action Coding System) will be assessed. This research also will test key mechanisms of craving relief that relate to existing theories of craving and addiction. In addition the project will monitor the durability of this predicted odor- induced craving-relief within a sinle experimental session and across sessions conducted on different days. This conceptually-driven research is motivated by neurobiological and behavioral research indicating the unique power of olfaction to trigger emotional memories and to fundamentally alter emotional states such as craving. The proposed project will examine interactions between emotional and cognitive processes that, while craving, may serve to hamper effective coping, and will set the stage for future research testing the impact of olfaction - alone or combined with other agents (e.g., nicotine patches) - on smoking cessation. Irrespective of the outcome, the proposed research using a novel set of measures will provide critical data regarding the interaction of emotional and cognitive processes during craving.

Cigarette craving is a key feature of smoking, which is the leading preventable cause of death. While smokers often recognize this danger, during moments of temptation the appeal of smoking rises and the habit persists. Unfortunately, research has struggled to develop treatments for craving relief. One approach showing promise is the strategic use of olfactory cues (OCs) to reduce craving. Two studies from the PI?s lab indicate that pleasant OCs reduce cigarette craving. Others have replicated this effect for food craving. Yet little is known about the nature of this urge-reducing effect, its underlying mechanisms, and individual differences that moderate its benefit. This application addresses FOA PAR 18-323: Fundamental Science Research on Mind and Body Approaches by testing this use of a natural product (OCs) to control craving and by testing the ?neurocognitive and behavioral mechanisms underlying? OC-induced craving relief (an FOA objective). Integrating theory and research derived from three disciplines rarely applied to smoking (olfaction, emotion, cognition), the project will test the impact of pleasant OCs on craving. Also pertinent to the FOA, this project will use innovative nonverbal measures of emotion and advanced multi-voxel pattern analyses (MVPA) (along with traditional fMRI analyses) to evaluate precise, theory-driven, underlying mechanisms (working memory, attentional engagement, delay discounting, response inhibition) for how OCs attenuate craving. The project will test why certain smokers may have trouble managing their craving and why OCs may be especially useful for a subset of smokers. Abstinent daily and nondaily smokers (n=250) will attend a multi-session experiment. They will rate a set of OCs on several dimensions, including pleasantness, mood, and related memories. They next perform a series of cognitive tasks during an fMRI session. They will receive in vivo smoking cues, which together with smoking abstinence, elicits robust urges. Next they will sniff an OC (one they had rated earlier as either pleasant or neutral) while urge and mood are assessed. MVPA will be used to generate ?neural fingerprints? for cognitive and affective processes in each smoker to probe the mechanisms underlying their own OC-induced urge reduction, and to inform matching of subjects to OCs. Subjects also will attend a behavioral session using a novel set of craving-related responses, including an urge pressure dynamometer and the Facial Action Coding System, to identify those most sensitive to urge relief, and to generate behavioral proxies for patterns of fMRI activity. As a secondary aim, we will test the effects of OCs on urge and smoking in the field. This translational study, drawing on fMRI and behavioral data regarding the unique power of OCs to alter affective states, will test key mechanisms of urge relief related to neurobehavioral addiction models. This interdisciplinary research also should stimulate future research testing the impact of OCs, alone or with other interventions (e.g., nicotine patches, cognitive therapies) on smoking cessation. Regardless of outcome, this research will provide important data on the interaction of emotional and cognitive processes during craving.