Investigation of Nicotine Seeking Behavior in Current Smokers

Participants could earn (via computer mouse 'clicks') money or cigarette puffs (preferred brand; provided by the study) across 11 independent choice trials. At the start of each trial, subjects selected either money or cigarette puffs on a computer screen. After each selection, subjects could earn one unit of that selection by satisfying the computer 'mouse' click requirement. The click requirement increased with each successive unit earned separately for cigarette puffs and money following a progressive ratio schedule (5, 12, 33, 100, 180, 340, 540, 835, 1220, 1660, and 2275 'mouse' clicks; identical schedule for both options and experimental sessions). Units were $0.25 money and 1 cigarette puff. Earned cigarette puffs were smoked at the end of the task and earned money was applied to the subject's study payment. The task was completed between 2:30pm and 3pm for each session.

Participants completed 5 blocks of a letter 2-back working memory task during proton functional magnetic resonance spectroscopy data acquisition from the left dorsolateral prefrontal cortex. The 2-back task consisted of a neurochemistry normalization period (passive viewing of a 3Hz flashing checkerboard; 208s) and alternating periods of passive visual fixation (centered fixation cross; 32s) and letter 2-back (64s; 4s instructions ['2-back'], 20 letters [3s/letter; 500ms on screen; 2500ms blank screen], 6 target letters). Changes in neurochemistry as quantified using LCModel were the primary outcome variable. 2-back response accuracy (% correct) and response latency (ms) were secondary outcomes.

Participants completed a neutral image vs. cigarette smoking-related image cued letter N-back task during functional magnetic resonance imaging acquisition. The task consisted of pseudo-randomly ordered blocks of 0-, 1-, and 2-back with either cigarette cues or matched neutral images behind each letter. Two 32s blocks of each task permutation were collected separated by 16s of blank screen (to minimize carry-over effects). Patterns of brain activation throughout the task was the primary outcome measure while N-back response accuracy (% correct) and response latency (ms) were secondary outcomes.

Well-validated self-report measure of nicotine withdrawal symptoms was measured (MNWS; Hughes and Hatsukami, 1986). Subjects were asked to rate 15 adjectives describing common nicotine withdrawal symptoms on a 5-point Likert scale reflecting symptom severity during the past 10 minutes from 0='not present' to 4='severe'. Mean scores were calculated across items with higher values (maximum=4) reflecting greater withdrawal symptom severity and lower scores (minimum=0) reflecting less severe withdrawal symptoms.

Well-validated self-report measure of subjective cigarette craving was measured (QSU; Cox et al., 2001). The self-report measure consists of 10-items with first-person statements describing one's desire to smoke a cigarette. Items are rated on a 7-point Likert scale: 1='strongly disagree' to 7='strongly agree'. Two sub-scales were considered separately; appetitive vs. relief-motivated craving. Sub-scales were quantified as a sum of items: higher scores reflected greater cigarette craving (both sub-scale scores range=5-35).

Well-validated self-report measure of state anxiety symptoms was measured (STAI; Spielberger, 1985). Subjects were asked to rate 20 first-person statements describing one's anxiety at this moment from 1='not at all' to 4='very much so'. State anxiety was quantified as a sum across items with higher scores reflecting more anxiety (range=20-80).

Well-validated measure of self-reported positive and negative affect was measured (PANAS; Watson et al., 1988). Subjects were asked to rate 20 adjectives on a 5-point Likert scale from 1='not at all or very slightly' to 5='extremely'. Two sub-scales were analyzed separately: positive vs. negative affect. Mean scores for each sub-scale were calculated and ranged from 1 to 5 with higher scores reflecting more positive or more negative affect.

Seated and resting systolic and diastolic blood pressure (BP; mmHg) was measured.

Seated and resting heart rate (HR; bpm) was measured.