Neuropharmacology of Emotion-Cognition Interaction in Nicotine Dependence

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DESCRIPTION (provided by applicant): Cigarette smoking remains the number one preventable cause of premature death in the U.S. In spite of these avoidable consequences, an estimated 60-90% of smokers motivated to attempt to quit relapse within the first year of their attempt. Research suggests that two of the primary reasons smokers relapse is 1) to attenuate stress and/or reduce negative affect and 2) to enhance or restore cognition. Therefore, understanding the neurobiological basis of smoking abstinence on affective and cognitive processes may provide new and valuable insights into the nature and treatment of tobacco addiction. The overarching objective of this proposal is to identify functional neuroanatomical correlates of changes in emotional and executive brain function during smoking abstinence, and to relate these changes to clinically relevant variables. We will measure changes in performance and regional blood oxygenation levels using fMRI while smokers and non-smokers complete a task designed to assess the effects of emotional stimuli on the detection of novel visual targets. In smokers, we will examine the effects of current drug state on the interaction between emotional processing and novelty detection by scanning participants 1) after smoking their regular number and brand of cigarettes (satiated condition) and 2) after 24 hr abstinence (deprived condition). Doing so will provide an assessment of how withdrawal modulates the neural substrates of emotion information processing. Data from non-smokers will allow us to compare brain activity during emotional information processing in normal healthy individuals with brain activity in smokers. We hypothesize that deprived smokers, when presented with negative emotional distractors will exhibit increased fMRI signal relative to smoking satiety in brain regions underlying 1) visual information processing (extrastriate cortex), 2) attention (e.g., anterior cingulate cortex), 3) evaluation of emotional information (e.g., posterior cingulate cortex), and 4) limbic/reward areas (e.g., amygdala). We further hypothesize that negative emotional distractors will disrupt processing of subsequent novel visual targets. The magnitude of this disruption will be greatest among deprived smokers, suggesting that withdrawal leads to greater interference of executive functioning by competing emotional processes. The results of this study will enhance our understanding of the neurobiological basis of tobacco withdrawal, inform treatment development, and generate additional hypotheses and research plans. PUBLIC HEALTH RELEVANCE: The results of this study will enhance our understanding of the neurobiological basis of tobacco withdrawal, inform treatment development, and generate additional hypotheses and research plans.