Nasir H. Naqvi, M.D., Ph.D. - US grants

DESCRIPTION (provided by applicant): Cue-induced urge is a hurdle to quitting cigarette smoking. The overall aim of this project is to understand the role of visceral representation in cue-induced smoking urge. The model for this process is based upon Damasio's framework for emotion, which points to visceral representation as a central component in the process of feeling emotion. Cue-induced urge is associated with cue-induced visceral responses. The insular cortex is hypothesized to map cue-induced visceral responses and convey this representation to conscious experience as a feeling of urge. This hypothesis will be tested in two studies. The first study will combine positron emission tomography, autonomic psychophysiology and self-report measurement in order to reveal the neural correlates of cue-induced smoking urge and to quantify the relationships between insular cortex activity, visceral responses and feelings of urge. The second study will look at the effects of focal lesions in smokers in order to determine if the insular cortex is necessary for visceral responses and/or feelings of urge.

Heavy drinking is the third leading cause of preventable death in the U.S. and is the second leading cause of disability among adults aged 24-44, however, there are two important gaps in current knowledge: 1) the mechanisms underlying less severe forms of AUD, like problem drinking (PD), are poorly understood, as are 2) the mechanisms underlying behavior change in PD, including both spontaneous (non-treatment) behavior change and behavior change that results from brief interventions (BI), which are particularly effective in PD . Here, we address the first gap by positing that PD have heightened incentive salience to alcohol cues (reactivity) and impaired ability to regulate incentive salience (regulation), compared to social drinkers (SD). We will test this hypothesis at a neural and behavioral level in the lab using functional MRI (fMRI) and in the natural environment ecological momentary assessment (EMA). We address the second gap by positing that whereas spontaneous behavior change in PD depends primarily upon the reactivity processes, behavior change in response to a BI depends primarily upon regulation processes. To these ends, we will recruit 100 PDs and 50 social drinkers (SD). At baseline, all participants will complete two weeks of EMA, perform an alcohol regulation of craving (ROC) task during fMRI scanning, and then complete 3 more weeks of EMA. The ROC task provides behavioral and fMRI measures of reactivity (e.g. increased ventral striatum activity and reports of cue-induced alcohol craving) regulation (e.g. control-related prefrontal activity and diminished craving). The analyses will test for group differences in baseline neural and environmental measures of reactivity and regulation. Next, PDs will be randomized to receive either a BI immediately or to receive the BI after 6 months, after outcomes are measured (the delayed intervention control, or DIC group). Both BI and DIC groups will complete an EMA protocol for the three weeks following assignment. Drinking outcomes will be assessed at 3 and 6 months. We expect that relative to SDs, PDs will show heightened neural measures of reactivity (e.g. elevated ventral striatum (VS) activation to alcohol cues in passive viewing conditions), and reduced neural measures of regulation (e.g. reduced activity in prefrontal control regions during regulation conditions) (Aim 1). In parallel, PDs will report higher levels of reactivity and lower levels of regulation in EMA measures, compared to SD, which will be correlated with fMRI measures (Aim 2). We predict that in the BI group, reduction in alcohol use will be moderated by the functioning of neural systems for regulation (e.g. dorsolateral PFC), whereas in the DIC group a persistence of alcohol use will be moderated by the functioning of neural systems for reactivity (e.g. VS) (Aim 3). Finally, we predict that in the BI group, changes in alcohol use will be mediated by changes in EMA measures of regulation and predicted by pre-treatment indices of regulation in the ROC task, whereas in the DIC group, changes in alcohol use will be mediated by changes in EMA measures of reactivity and predicted by pre-treatment measures of reactivity in the ROC task (Aim 4).