Cognitive and Affective Mechanisms Underlying an Olfactory Approach to Modify Cigarette Craving

The investigators aim to conduct a comprehensive analysis of craving and to test the impact of pleasant olfactory cues (OCs) on craving relief. Towards these aims, this study will integrate four sources of data: (a) individual differences thought to relate to craving; (b) neural responses to cognitive tasks and behavioral (e.g., Facial Action Coding System measures) reactions to OC sampling; (c) fMRI and behavioral responses to post-smoking cue OC exposure; and (d) EMA data related to craving and smoking. The investigators will embed findings within neurobehavioral addiction theories (dual-systems, iRISA) and will try to identify individuals who may benefit most from OC-based interventions. Most of the study procedures are observational in that they are intended to measure without influencing any health-related outcome. One study procedure meets the revised NIH guidelines for an intervention, in that craving, behavior, and brain activity are measured while participants are presented with either a pleasant or a neutral (blank) olfactory cue in a between-subjects design. The details of study procedures are outlined in the following paragraphs.

Overview Data will be collected over a series of three laboratory sessions. Nicotine-deprived smokers with varying levels of interest in quitting will sample a set of OCs. Participants will be exposed to smoking cues to induce peak cravings and then receive one of the previous OCs (randomly assigned to either a pleasant or neutral OC). This study will use a between-subjects design in which participants will complete several tasks during two experimental sessions, with some tasks better suited to the behavioral and others to the fMRI session. A week-long EMA protocol will follow, within which the effect of OCs on craving and smoking will be assessed. All participants will complete all study procedures.

Procedures The first study contact includes a telephone screening to assess preliminary inclusion and exclusion criteria, including major MRI-related exclusion criteria such as metal in the body. Eligible and interested participants will then visit the lab to complete an approximately 1-hour visit that includes a standardized assessment. Data collected during this visit will be used primarily to characterize the sample.

In both of the following experimental visits, participants will complete a series of common procedures. First, participants will be asked to abstain from smoking for at least 8-hrs prior to each visit. To ensure abstinence, participants will report when they last used nicotine and record carbon monoxide (CO). Participants will also present their cigarette pack and lighter, and complete a brief assessment of baseline craving and mood with standard measures used in the Principal Investigator's prior work. Additionally, participants undergo an odor sampling procedure. They will be asked to sniff 8 OCs; after each one, they will provide via structured interview ratings of pleasantness, intensity, familiarity, evoked emotions, mood, and report any associations or memories to the OC. OC presentation order is randomized. Participants will then undergo a cigarette cue exposure to induce peak cravings. Participants in the pleasant OC condition will then sniff an OC they rated as pleasant, while those randomized to the neutral condition will receive an odor blank. Outside of these procedures, the two experimental sessions differ.

The first experimental session will occur within approximately 1-week (potentially more depending on scanner availability) of the screening session and will include a roughly 60-minute fMRI scan. The first part of the scan will involve structural, resting state, and task-based data collection (e.g., Go/No-Go to assess response inhibition; cigarette cue exposure). This will allow for identification of individually specified cognitive brain states linked to addiction-related processes (i.e., neural fingerprints). Then, neural activity (BOLD) and functional and effective connectivity for identified regions of interest (ROI) will be measured during a smoking cue exposure manipulation (to induce craving) followed by olfactory cue administration. These data will be used to examine the disruption of the craving brain state by the pleasant, compared to the neutral, olfactory cue.

In the second experimental session, participants will undergo a series of behavioral tasks. This again includes a smoking cue exposure manipulation followed by administration of either the pleasant or neutral olfactory cue. To examine the impact of pleasant vs. neutral OCs on craving, participants will provide urge ratings and behavioral measures of urge (i.e., craving as measured through a pressure-sensitive squeeze device, and facial affect) throughout this procedure. Behavioral measures of affect will also be collected during the OC sampling procedure to allow for an examination of how emotional responses to pleasant olfactory cues mediate the impact of olfactory cues on craving.

The final study procedure involves a 7-day ecological momentary assessment (EMA) protocol in which participants will monitor their cigarette cravings and the investigators will collect pilot data to assess how well pleasant vs. neutral olfactory stimuli will control these real-life cravings.

The primary outcomes of interest throughout these experimental sessions involve the impact of pleasant vs. neutral olfactory cues (i.e., odor blanks) on urge to smoke. The investigators are also interested in determining if the patterns of neural activation during smoking cue exposure and during olfactory cue exposure are more similar for those randomized to the neutral OC condition than to the pleasant OC condition. Briefly, analyses will include representational similarity analysis, in which the similarity of activity patterns (neural fingerprints) for different brain states (craving, post-cigarette cue odor) in each subject, is measured through Pearson correlation. Brain states are represented by the pattern of beta coefficients across the 89 atlas regions that underlie each phase of the fMRI session (e.g., while the subject is holding a cigarette to induce craving). These patterns are correlated with each other (giving one Fisher-Z transformed r coefficient per subject), and the resulting correlation coefficients are compared in a group analysis that tests for a statistically significant difference between the pleasant odor group and the neutral/odor blank group. Secondary outcomes of interest include equivalent analyses that calculate the similarity between the post-cigarette cue odor-induced brain state with brain states observed for each of the behavioral tasks completed in the fMRI ( i.e., N-back, Posner Cueing, Delay Discounting, Go/No-Go) in order to quantify and statistically contrast the relative presence of key cognitive and affective processes.