Baseline-Dependent Moderation of the Effects of Nicotine on Spatial Attention

The below project was presented at the 16th Annual Duke Nicotine Conference in September 2010 and will be submitted as a manuscript to Nicotine & Tobacco Research

Jonathan Hammersley, Ph.D., David Gilbert, Ph.D., Adam Rzetelny, Ph.D., Robert Radtke, Ph.D., & Norka Rabinovich, B.A.

ABSTRACT

The present study assessed the effects of nicotine on spatial attentional orienting in 52 habitual smokers (27 females and 25 males), using a covert attention (arrow-cued) target detection task (COAT). Analysis of covariance (ANCOVA) and a subsequent analysis of variance (ANOVA) demonstrated that relative to placebo, 14 mg nicotine patch produced shorter reaction times (RTs) across task conditions. In addition, individuals slower RTs in placebo condition task performance, based on their mean performance on the two placebo days, benefitted more from nicotine across conditions than did those who had faster RTs in placebo performance. Nicotine also enhanced the validity effect (shorter RTs to validly cued vs. invalidly cued visual field), but the validity effect benefit due to nicotine did not differ as a function of overall baseline placebo vigilance performance. Findings support the view that nicotine enhances spatial attentional orienting to a greater extent in individuals who are low (slower) during placebo abstinent (baseline) conditions. Results are discussed in terms of individual differences in baseline performance, situational arousal / habituation and associated mediators and moderators.

BACKGROUND

Experimental studies indicate that nicotine and other cholinergic drugs affect a variety of attentional systems (e.g., Levin & Simon, 1998). The covert attention task (COAT) requires central fixation centrally while covertly directing attention to one side of a screen when cued by a central arrow, and one responds to a peripheral target (Posner, 1980; Posner & Petersen, 1990). Reaction times (RTs) to targets are typically more rapid when targets are preceded by valid versus invalid cues (validity effect). Research examining effects of nicotine on spatial attention are somewhat limited or inconsistent and typically use a different, peripherally-cued version of the COAT. Some studies suggest that nicotine and other cholinergic agonists enhance visuospatial reorienting during the COAT and related tasks (Thiel, Zilles, & Fink, 2005). A few studies suggest that in smokers nicotine may reduce reaction times for invalid trials without influencing valid trials (Witte, Davidson, & Marrocco, 1997) or have a general speeding effect, but no effect specifically associated with attentional orienting (Hahn, Ross, Yang, Kim, Huestis, & Stein 2007). 

Griesar et al. (2002) reported that, in nonsmokers, transdermal nicotine, relative to placebo, reduced RTs to targets during the COAT and was associated with a trend for nicotine to increase the validity effect. However, this latter effect only approached statistical significance, possibly due to small sample size (N= 12). As the effects of nicotine in nonsmokers frequently differ from the effects in smokers (Heishman, Henningfield, & Singleton, 2002; Newhouse, Potter, & Singh, 2004), these prior findings make it important to assess the effects of nicotine on attentional orienting in smokers using the standard COAT.

Eysenck (1980, 1997) proposed that nicotine’s effects are moderated by pre-drug baseline brain activation level that in turn is influenced by a combination of genetically influenced dispositional traits, situational arousal and fatigue potential of the environment. Consistent with baseline theory, Patterson et al. (2010) recently found that poorer working memory on a rapid information processing task (the N-Back) during abstinence predicted more rapid resumption of smoking. The present investigation assessed the possibility that inconsistency of the effects of nicotine on attentional orienting may depend on individual differences in be baseline attentional functioning, such that individuals with poor placebo baseline performance would benefit more from nicotine than those with better placebo baseline functioning (See Perkins, 1999 and Newhouse, Potter, & Singh, 2004, for a review of evidence supporting this effect for nicotine’s influence on attention generally).

METHODS

Participants

Participants used in analyses were 27 female and 25 male smokers with a mean age of 23.3 years (7.1 SD, 18-47 range) who smoked an average of 18.38 (5.4 SD, 10-40 range) cigarettes per day. Nicotine dependence was assessed with the FagerströmTest of Nicotine Dependence (FTND; Heatherington, Kozlowski, Frecker, & Fagerström, 1991). The mean FTND score was 4.36 (1.5 SD, 1-8 range), indicating a moderate degree of dependence. Two males and two females were African Americans and the remaining participants were Caucasian.  

Participants were recruited by newspaper ads and postings in the university community. Exclusion criteria included smoking fewer than 10 cigarettes per day for the past year, habitual cigarette estimated nicotine deliveries of less than 0.6 mg, reported use of psychoactive drugs or medications other than caffeine, marijuana, and alcohol, excessive alcohol use (more than 28 drinks/week), age less than 18 or more than 48 years, non-English speaking, atypical sleep cycles, pregnancy, and serious medical or uncorrected visual problems. Age was restricted because RTs become slower and sight poorer with age. Participants (N = 8) exceeding the maximum allowable CO or more than 3 drinks of alcohol the evening before, or reporting fewer than 5 hours of sleep, illness, or other drug use, including marijuana,resulted in rescheduling the session.

Design and Procedure
Participants were instructed not to smoke for 12 hours preceding each the experimental session, and only those who adhered to this abstinence were included in data analysis (CO-biochemically verified). During each of four experimental sessions (following two orientation sessions) participants completed the Posner (1980) COAT twice. Experimental days were separated by a minimum of 48 hours and a maximum of 5 days. The study was double blind for the nicotine versus placebo status of the patches, and patches and task orders were counterbalanced across sessions. Each participant received a nicotine patch on one of the first two experimental sessions and a second nicotine patch during one of the last two experimental sessions.

Tasks
Each COAT consisted of 180 trials, with left, right and no-arrow cues each appearing on 60 trials within a block. Of the 120 arrows, 96 (80%) were valid and 24 (20%) were invalid. Each trial consisted of a 1000 ms prompt to blink, a 500 ms central cross, a central arrow cue pointing left or right or absent, and an asterisk presented left or right of the cross (Figure 2). Instructions were to respond as rapidly as possible without sacrificing accuracy by pressing either the left or right key on a response box, and RTs were recorded to the nearest millisecond (ms).

RESULTS

Covert Attention Task (COAT)The covariate in a preliminary analysis of covariance (ANCOVA) was mean placebo RT time across all condition (experimentally manipulated independent factors). Both this initial ANCOVA and a subsequent ANOVA use the following factors: Nicotine (nicotine vs. placebo) × Validity (valid vs. invalid cue) × Patch Exposure (first vs. second day of exposure to the nicotine and placebo patches) × Visual Field (left vs. right target location) × Gender × Exposure (first two vs. last two experimental sessions). The ANOVA also included an additional between-subjects factor—Placebo-RT to which individuals were assigned based on their performance on the mean of the two placebo days RTs (bottom, middle, and top thirds of mean placebo RT).

The ANOVA revealed significant main effects for Validity and Nicotine, as well as significant Nicotine × Placebo-RT and Nicotine × Validity interactions. As expected, there was a highly significant main effect of Validity, F(1,46) = 288.030, p < .001, partial eta2 = .86, such that validly cued targets were associated with shorter RTs than invalidly cued targets. Nicotine was associated with a shorter (quicker) RTs to all cued targets than placebo (270.3ms vs. 290.4ms), F(1,46) = 80.96, p < .001, partial eta2 = .64; however, these effects of nicotine were moderated by cue validity such that nicotine shortened RTs more in the valid than invalid condition (Fig 1), Nicotine × Validity, F(1,46) = 5.909, p = .019, partial eta2 = .114. Consistent with the ANCOVA results, the effects of nicotine were also moderated by mean placebo-RT, Nicotine × Placebo-RT level, F(2,46) = 6.373, p = .004, partial eta2 = .217, such that longer RTs on placebo were associated with greater RT benefits (Figure 3).  
Relative to placebo, RT-reducing effects of nicotine were greater on the second exposure to nicotine (session 3 or 4) than on the first exposure (session 1 or 2) across valid and invalid conditions, , F(1,46) = 6.442, p = .015, partial eta2 = .123. There were no significant main effects of Gender involving Nicotine on RTs, and ANCOVAs using FTND dependence scores and age as covariates did not result in impact on main effects or interactions.

 

DISCUSSION

Overall, our findings are supportive of the hypothesis that NRT can enhance covertly cued attentional orienting, but that these effects are greater in those with slower placebo RTs, and are greater upon second testing, possibly due to lowered situational arousal potential/habituation to the experimental setting. Nicotine enhanced the validity effect, the tendency to benefit from valid relative to invalid spatial cues. This is consistent with the findings of Griesar et al. (2002) who found similar effects in nonsmokers. Present effects of nicotine on the COAT performance were placebo-baseline and task practice dependent.  

The present study was limited by a relatively modest in sample size and was not a fully representative sample of smokers, with respect to age, length of smoking history, and race. Effects of nicotine in very light, heavier, older, and substance abusing smokers were not assessed, nor can effects be generalized to ex-smokers and non-smokers.  While we refer to the effects of nicotine relative to placebo, the observed effects could reflect either effects of nicotine withdrawal alleviation in habitual smokers or inherently beneficial effects of nicotine.