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

The proposed study uses fMRI and behavioral measures in and outside the laboratory to investigate the neurobehavioral mechanisms underlying the impact of pleasant olfactory cues (OCs) on cigarette craving. The investigators plan to randomize 278 participants to a pleasant OC condition or an odor blank (neutral) condition and due to anticipated drop out expect to run 250 adult (half female) smokers, including both daily and nondaily smokers through the protocol. This study involves three visits. In the first visit, participants will complete a baseline breath carbon monoxide reading, a brief odor threshold test, and complete a series of self-report measures. In the next session, participants who are 8-hrs deprived of nicotine will undergo a 60-minute fMRI scan that will include structural, resting state, and task-based data collection. The fMRI task involves completing a series of tasks designed to index responses linked to key neural networks found to relate to addiction (e.g., reward processing, working memory). Participants will also be exposed to smoking cues to heighten craving and then depending on their condition (randomly assigned) will either receive a pleasant or neutral (odor blank) OC. In the third session, behavioral data will be collected to test the impact of either a pleasant or neutral OC on cigarette craving using self-reported urge and behavioral measures linked to craving. Finally, for pilot purposes designed to offer data for a subsequent clinical study (beyond this study), participants will additionally complete a 7-day ecological momentary assessment (EMA) protocol in which they will monitor cigarette craving and initial data will be collected outside the laboratory to evaluate the impact of OCs on naturally occurring craving. It is hypothesized that pleasant OCs will disrupt craving brain states and attenuate craving (as compared to neutral olfactory cues). Further, it is hypothesized that individual variation in neural responses to cognitive and affective tasks will reveal variation in mechanisms underlying pleasant OC craving reduction and that individual differences will moderate pleasant OC-induced craving relief. Finally, it is also expected that emotional responses to pleasant OCs will mediate the impact of OCs on craving and smoking-related processes.

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.

Eligibility Criteria:
Inclusion Criteria:

* Aged 18-49
* Right-handed
* Fluent in English
* Intact sense of smell
* Pass an MRI safety screening and along these lines will need to be 250lbs or less to safely enter the MRI
* No drug dependence outside of nicotine or caffeine
* Must fit into one of two categories of smokers, daily or nondaily, as confirmed by verbal self-report and a baseline CO reading; Daily smokers: must smoke 10-30 cigarettes per day for at least 12 months, Nondaily smokers: must smoke for 1-14 days of the last 30 days with no more than 20 cigarettes a day
* Need to have access to a working smartphone to complete the ecological momentary assessment portion of the study

Exclusion Criteria:

* Medical conditions that contraindicate nicotine use
* Not fluent in English
* Illiterate
* Current neurological or psychotic disorders
* Current psychoactive drug use
* MRI contraindications such as stroke history, pregnancy, metal in the body, history of aneurysms, or serious head injury
* Individuals will also be excluded if they report any allergies to the odors used in our study.
* Baseline CO readings will need to be consistent with our criteria for daily and nondaily smokers for participants to be considered eligible. Specifically, we plan to rule out extremely heavy smokers (nondeprived CO \> 55, for whom the smoking abstinence requirement may be too extreme to allow a sensitive test of our OC manipulation) and daily smokers with a nondeprived CO reading \<10 PPM as this would raise concerns that they do smoke enough to be classified as a daily smoker.