PROJECT SUMMARY The modern rise in obesity rates coincides with the increased advertising and availability of palatable foods. Conditioned responses to these ubiquitous food cues, such as craving or brain activity, are known collectively as food cue reactivity (FCR). Individual differences in FCR strength are associated with obesity (defined by Body Mass Index or BMI) and predict food intake and weight change. However, it is unclear why some individuals have stronger FCR than others. The central hypothesis of this proposal is that odor imagery ability is one factor that drives FCR strength, which in turn promotes risk for overeating and weight gain. Rationale for this hypothesis stems from a prominent theory that mental imagery is highly involved in the generation of craving. There is also greater variation in the ability to imagine odors compared to visual objects and scenes, and a preliminary study showed that this variation in odor imagery ability is positively correlated with BMI. However, odor imagery ability in that study was measured with a self-report questionnaire, and it is poorly understood how well this subjective measure maps onto actual ability. In addition, whether odor imagery ability influences feeding and weight gain is unknown. Guided by these strong preliminary data and critical gaps in knowledge, the current proposal will quantify odor imagery ability in two objective ways: (1) psychophysically, as the interference effect by which imagining the smell of one odor impairs the actual detection of another at a weak concentration; and (2) neurally, as the decoding accuracy with which brain patterns generated while smelling real odors can predict those while imagining odors and vice versa. Measures of FCR will include cue-induced craving and brain response to food cues. Ultimately, the specific aims include testing if objective odor imagery ability correlates with (1) self-reported ability and BMI, (2) FCR, and (3) cue-potentiated feeding or weight change over 12 months. These aims will elucidate how odor imagery contributes to FCR and obesity risk. If the hypothesis is supported, then odor imagery ability will serve as a new target to reduce FCR in susceptible individuals. The project will be conducted in Dr. Dana Small’s laboratory located at Yale University and affiliated with Yale’s Interdepartmental Neuroscience Program (INP) and the Modern Diet and Physiology Research Center (MDPRC). This environment will provide training in unique research skills, such as mastering the use of Dr. Small’s olfactometer to deliver odors during neuroimaging and performing advanced analyses on high-performance computing clusters. A collaboration with Dr. Hedy Kober will refine the applicant’s skillset in machine learning techniques. Involvement in the MDPRC – which is a small and collaborative group focused on understanding the impact of diet on health and brain function – will facilitate frequent exposure to new research in the field and the abi...