The primary objective of this revised proposal is to characterize more fully when, how, and in whom nicotine modulates affect and attention to emotional stimuli. It is hypothesized that nicotine attenuates attentional bias to negative emotional stimuli and associative processing of such stimuli, thereby decreasing negative emotional states. This attenuation of negative attentional bias and associative processing by nicotine is hypothesized to result from nicotine's enhancing attentional and associative bias to positive and neutral stimuli that in turn compete with and inhibit negative affect-related processing. Nicotine-induced attentional and associative biasing is hypothesized to occur most strongly in situations where the frequency of negative stimuli is moderate or low and the subject has a significant degree of freedom of attentional choice. Thus, the effects of attentional choice (two-picture viewing) versus no-choice (one picture viewing) conditions on nicotine's ability to reduce negative affect will be assessed by presenting blocks with a series of 64 single or dual pictures on a computer. Mood will be assessed before and after each picture series block. The frequency of negative pictures in these series will be manipulated (either 16 [low frequency] or 48 [high frequency]). In the no-choice task, single pictures will be presented centrally on the computer screen. In the two-choice task, dual picture images will be presented simultaneously in the left and right visual field. Picture series blocks (64 single or dual pictures) will consist of the following 4.5 sec. sequence: the word """"""""blink"""""""", a fixation cross, and a picture (or dual picture). In the two-choice condition, subjects will be instructed to allocate as much or little of their gaze time to a given picture, but to always be gazing at one of two pictures. In the no-choice condition, subjects will be required to maintain a 3 sec. gaze at each picture. Neutral or positive pictures will be interspersed in both the two-choice and no-choice tasks. Eye-gaze patterns during the two-choice task and no-choice task will be obtained with an infrared, computerized tracking system. In the two-choice task, maximal dysphoria-reducing effects of nicotine are predicted to occur during blocks with a high frequency of negative pictures. Nicotine is predicted to reduce gaze directed toward negative pictures and to enhance attention to positive pictures. In the no-choice task, nicotine is expected to have maximal dysphoria-reducing effects when a low frequency of negative pictures is combined with intervening positive pictures. Potential moderating influences of gender, smoker-nonsmoker status, and individual differences in trait anxiety, depression, and anhedonia will be assessed with regression analyses. This work will use new experimental procedures and technologies, including the precise assessment to individual differences in continuously monitored eye-gaze patterns with an infrared, computerized tracking system. The new knowledge derived from these studies will be useful in developing empirical model-based treatment strategies aimed at increasing smoking abstinence.
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