Psychopharmacology DOI 10.1007/s00213-014-3761-5
ORIGINAL INVESTIGATION
Nicotine reduces distraction under low perceptual load Oliver Behler & Thomas P. K. Breckel & Christiane M. Thiel
Received: 19 July 2014 / Accepted: 24 September 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract Rationale Several studies provide evidence that nicotine alleviates the detrimental effects of distracting sensory stimuli. It is been suggested that nicotine may either act as a stimulus filter that prevents irrelevant stimuli entering awareness or by enhancing the attentional focus to relevant stimuli via a boost in processing capacity. Objectives To differentiate between these two accounts, we administered nicotine to healthy non-smokers and investigated distractor interference in a visual search task with low and high perceptual load to tax processing capacity. Methods Thirty healthy non-smokers received either 7 mg transdermal nicotine or a matched placebo in a double blind within subject design 1 h prior to performing the visual search task with different fixation distractors. Results Nicotine reduced interference of incongruent distractors, but only under low-load conditions, where
Electronic supplementary material The online version of this article (doi:10.1007/s00213-014-3761-5) contains supplementary material, which is available to authorized users. O. Behler : T. P. K. Breckel : C. M. Thiel (*) Biological Psychology, Department of Psychology, European Medical School, Carl-von-Ossietzky Universität Oldenburg, Ammerländer Heer Str. 114-118, 26111 Oldenburg, Germany e-mail: [email protected] O. Behler Medical Physics, Department of Medical Physics and Acoustic, European Medical School, Carl-von-Ossietzky Universität Oldenburg, Oldenburg, Germany C. M. Thiel Cluster of Excellence “Hearing4all”, Carl von Ossietzky Universität Oldenburg, Oldenburg, Germany C. M. Thiel Research Center Neurosensory Science, Carl-von-Ossietzky Universität Oldenburg, Oldenburg, Germany
distractor effects were large. No effects of nicotine were observed under high-load conditions. Highly distractible subjects showed the largest effects of nicotine. Conclusions The findings suggest that nicotine acts primarily as a stimulus filter that prevents irrelevant stimuli from entering awareness in situations of high distractor interference. Keyword Nicotine . Attention . Psychopharmacology . Distraction . Perceptual load . Non-smoker . Drug . Acetylcholine
Introduction Numerous studies provide evidence that nicotine can improve cognitive performance in human smokers as well as in patients with attention deficit hyperactivity disorder (ADHD), schizophrenia and Parkinson’s and Alzheimer’s Diseases (Newhouse et al. 2004; Levin et al. 2006). In contrast, nicotine studies investigating healthy non-smokers have often yielded controversial or weak results (Foulds et al. 1996; Levin et al. 1998; Heishman and Henningfield 2000; Newhouse et al. 2004), supporting the notion that performance enhancements under nicotine might rather reflect a reversal of pathological or deprivation-induced deficits. In a recent meta-analysis of 40 studies in healthy non-smokers or minimally deprived smokers, however, Heishman et al. (2010) concluded that the beneficial effects of nicotine on attention are likely genuine and not confounded by withdrawal relief. Difficulties in finding significant results in non-smokers might arise from large interindividual differences in nicotine’s behavioural effects, which have been suggested to depend on “baseline characteristics” before drug exposure (Perkins 1999; Newhouse et al. 2004; Poltavski and Petros 2006; Giessing et al. 2007; Potter et al. 2012; Knott et al. 2013).
Psychopharmacology
Improvements of attentional functions under nicotine have been documented in many sustained and selective attention paradigms in smokers and non-smokers (e.g. Wesnes and Warburton 1984; Foulds et al. 1996; Mancuso et al. 1999; Lawrence et al. 2002; Trimmel and Wittberger 2004; Rycroft et al. 2005; Thiel et al. 2005; Meinke et al. 2006; Hahn et al. 2009) and are independent of smoking status (Trimmel and Wittberger 2004). The processes underlying these attentional improvements are, however, less clear. Kassel (1997) suggested that nicotine may enhance attentional processing by two different (not mutually exclusive) mechanisms, either by acting as a stimulus filter that prevents irrelevant stimuli from entering awareness or by enhancing the attentional focus to relevant stimuli via a boost in processing capacity. Most experimental approaches where subjects had to attend to relevant and ignore irrelevant stimuli did not intend to tease apart these two competing explanations but rather aimed at showing performance-enhancing effects of nicotine in the presence of distractors. These studies provide evidence that nicotine or specific α4β2 agonists alleviate the detrimental effects of distracting sensory stimuli in monkeys (Prendergast et al. 1998) and rodents (Hahn et al. 2002; Howe et al. 2010) performing visual tasks. There is also some evidence for reduced distraction in human smokers and non-smokers (Grobe et al. 1998; Trimmel and Wittberger 2004); see however Knott et al. (2006, 2009, 2011) for an absence of behavioural effects or Vangkilde et al. (2011) for increased distractibility. Hahn et al. (2002) suggested that the nicotine-induced distractor resistance may be mediated by an improved ability to focus attention on or, alternatively, to redirect attention back to task-relevant stimuli if it had been shifted towards the distractor. Nicotine’s well-documented ability to facilitate the reorienting of visuospatial attention after invalidly cueing the target location in visuospatial cueing tasks (Witte et al. 1997; Murphy and Klein 1998; Phillips et al. 2000; Thiel et al. 2005; Meinke et al. 2006; Thiel and Fink 2008; Vossel et al. 2008) conceivably supports the latter explanation. A recent electrophysiological study that investigated the effects of nicotine in a visual task with auditory distractors provides further evidence for a drug-induced improvement of re-focusing on taskrelevant stimuli after distraction, since amplitudes of the reorienting negativity were bigger under nicotine (Knott et al. 2011). The electrophysiological data under nicotine, however, also indicated significantly decreased amplitudes of the P3a component when compared to placebo (Knott et al. 2011; Mathalon et al. 2014). Because the P3a component is elicited by involuntary shifts of attention to task-irrelevant stimuli, this finding corroborates the idea that nicotine acts as a stimulus filter. To better differentiate between an improved ability to focus attention vs preventing involuntary shifts of attention to task-irrelevant stimuli, we investigated distractor interference in a visual search task with high and low
perceptual load (Lavie and Cox 1997; Beck and Lavie 2005). Studies using such tasks have repeatedly shown that distractor interference is reduced under high perceptual load when, according to the view of Lavie and colleagues, all available resources are exhausted. In contrast, under low perceptual load, spare capacity would spill over, resulting in perception of task-irrelevant stimuli. If nicotine acts primarily as a stimulus filter that prevents irrelevant stimuli entering awareness, one would predict that nicotine exerts its effects mainly in situations where irrelevant stimuli enter awareness easily, i.e. nicotine should reduce distractor processing under low-load conditions. If nicotine, however, heightens the attentional focus to relevant stimuli via a boost in processing capacity, one would predict that nicotine should have stronger effects in conditions where available capacities are exhausted, i.e. nicotine should increase available resources in high load conditions and hence increase distractor processing. Moreover, given the often reported baseline-dependent effects of nicotine mentioned above, we expected that behavioural effects of nicotine would depend on interindividual differences in baseline performance.
Methods Participants Thirty healthy non-smokers (13 males, 17 females; age range 18–35 years, mean and SD: 23.5±2.8 years), recruited at the University of Oldenburg, gave informed consent to participate in the study. A clinical evaluation was first carried out to ensure that participants had no conditions contraindicative for nicotine administration. Subjects were screened for major medical illness, including neurological and psychiatric disorders, history of alcohol and drug use and pregnancy. Ethics approval was obtained from the ethics committee of the German Psychological Association (DGPs). All procedures were performed in accordance with the Declaration of Helsinki (2008). Non-smokers were recruited to avoid confounding effects of nicotine abstinence on cognitive effects, that is, the possibility of reversing a deprivation-induced attentional deficit, rather than increasing attentional processes per se. Only volunteers who reported to have never been regular smokers were allowed to participate. All participants were right-handed (Oldfield, 1971; LQ>49), had normal, or corrected to normal, vision, no prior history of neurological or psychiatric disease and were free of medication except for contraceptives. Participants were asked to abstain from alcohol for 1 day before the experiment and from caffeine for at least 1 h prior to testing. One participant was excluded due to strong nausea following nicotine treatment and was subsequently replaced by a newly recruited subject.
Psychopharmacology
We used a within-subjects design. Each participant attended two experimental sessions, separated by at least 1 week. Drug administration was placebo-controlled and double blind and the order of pharmacological treatment was counterbalanced across subjects. Nicotine was delivered via a transdermal system (Niquitin® Clear 7 mg, GlaxoSmithKline Consumer Healthcare GmbH). A pharmacologically inactive, similar patch (Draco wound healing patch) served as placebo. Either patch was placed on the participants’ back right above the waist and was removed after 1 h, a few minutes before the start of the experimental task. Given a linear dose-concentration relationship of the delivery system, plasma levels achieved in the present study are expected to be about 3 ng/ml with a halflife of 3.2 h (Gorsline et al. 1992; Gorsline et al. 1993). Testing took place between 9 am and 5 pm. Placebo and nicotine sessions were always performed at the same time in each volunteer.
which alternated and had breaks of 30 s in between them. Each block consisted of 18 trials per distractor condition, yielding a total of 90 trials per block. Participants were asked to respond by pressing the left arrow key on a millisecond accurate keyboard with their right index finger if the target was an X, and by pressing the right arrow key with their right middle finger if the target was a Z. Both speed and accuracy were emphasized. Subjects were also instructed to ignore the distractors and were told that these were irrelevant to the task. Feedback was given in the form of either of two different tones - one for correct responses and the other for incorrect responses or the failure to respond within the maximum response time of 2 s. At the end of each experimental block, participants were additionally informed on the screen about their average reaction time (RT) and accuracy. The whole task was completed in approximately 30 min. In both sessions, participants completed a 5-min training session, consisting of 4 blocks with 20 trials each and alternating perceptual load conditions.
Stimuli and experimental paradigm
Statistical analysis of behavioural data
We employed a visual search task with high and low perceptual load and foveal distractors (Beck and Lavie 2005; Espeseth et al. 2010). The experiment took place in a darkened, sound-proof testing chamber. Stimuli were presented on a 19-in. monitor (DELL 1905FP) using the Cogent 2000 toolbox (Wellcome Department of imaging Neuroscience) for MATLAB (Version 7.1, The MathWorks Inc., Natick, MA, USA,). Viewing distance was approximately 60 cm. All stimuli were presented in light grey colour on a black background (see Fig. 1). Participants were instructed to maintain fixation on the centre of the screen, as indicated by a small cross, throughout the task. At the beginning of each trial, a circular array of six letters with a radius of 2° around the centre was presented for 100 ms. Target letters (X or Z) appeared randomly but with equal probability in one of the six positions. The other five positions were occupied by non-targets. In the low perceptual load condition, non-targets were always capital Os. In the high load condition, non-targets were capital A, H, K, N and Vs, arranged in random order with equal probability. In 80 % of the trials, the fixation cross was replaced by different task-irrelevant distractors. The distractor could either be congruent (e.g. X when the target was an X), incongruent (e.g. X when the target was a Z), neutral (a capital O) or physically salient (a black square). In 20 % of the trials, the fixation cross remained unchanged (“no distractor”/control condition). Targets, non-targets and distractors subtended 0.4°×0.5° of visual angle (except for the physically salient distractor, which subtended 0.5°×0.5° of visual angle). Following a time interval jittered around 3000 ms (±500 ms) after each stimulus presentation, the next trial began. Trials were arranged in three low-load blocks and three high-load blocks
Median RT and accuracy (correct responses/number of trials) were calculated for each participant as a function of drug (placebo, nicotine), load (low, high), and distractor condition (no distractor, congruent, incongruent, neutral, physically salient) and submitted to a repeated measures analysis of variance (ANOVA) with drug order (placebo-nicotine, nicotineplacebo) as between group factor. Significant interactions were further investigated by post hoc t tests. Incorrect responses were excluded from RT analyses. To investigate whether nicotine decreases distractor processing under low load and/or increases distractor processing under high load we focused on the difference between incongruent and no distractor trials only since distraction costs are highest with incongruent distractors. Two planned ANOVAs on the low and high load condition were performed which compared the distractor effect (ΔRT incongruent distractor, no distractor) under nicotine and placebo with drug order as between group factor. To investigate baseline-dependent effects of nicotine, we tested with a linear regression analysis whether the slope of the regression is significantly smaller than unity (see (Perkins 1999)).
Drug administration
Subjective and physiological measures To investigate side effects of the nicotine treatment, participants’ subjective mood and physical symptoms as well as heart rate and blood pressure were assessed three times in both sessions: Upon arrival (t1), immediately after removal of the placebo or nicotine patch (t2) and at the end of the experiment (t3). Subjective mood was assessed with visual analogue scales (Bond and Lader 1974). Rating scores were
Psychopharmacology Fig. 1 Illustration of the paradigm. Illustrated is the time course of two successive trials (e.g. a no distractor trial and an incongruent distractor trial) in the low- and high-load condition
grouped into the three factors “alertness”, “contentedness” and “calmness”, according to Bond and Lader (1974). Subjective physical symptoms (including headache, dizziness and nausea) were assessed with a customized checklist. At the end of each testing session, volunteers were asked to guess whether they received the nicotine or placebo patch. Mood scores, heart rate and blood pressure were submitted to a repeated measures ANOVA with drug (placebo, nicotine) and time (t1, t2, t3) as within-subjects factors.
Results Subjective and physiological measures Five subjects reported mild dizziness immediately after removal of the nicotine patch. These adverse effects, however, wore off towards the end of the session. Heart rates decreased over time (main effect of time F(2,58)=16.8, p
ORIGINAL INVESTIGATION
Nicotine reduces distraction under low perceptual load Oliver Behler & Thomas P. K. Breckel & Christiane M. Thiel
Received: 19 July 2014 / Accepted: 24 September 2014 # Springer-Verlag Berlin Heidelberg 2014
Abstract Rationale Several studies provide evidence that nicotine alleviates the detrimental effects of distracting sensory stimuli. It is been suggested that nicotine may either act as a stimulus filter that prevents irrelevant stimuli entering awareness or by enhancing the attentional focus to relevant stimuli via a boost in processing capacity. Objectives To differentiate between these two accounts, we administered nicotine to healthy non-smokers and investigated distractor interference in a visual search task with low and high perceptual load to tax processing capacity. Methods Thirty healthy non-smokers received either 7 mg transdermal nicotine or a matched placebo in a double blind within subject design 1 h prior to performing the visual search task with different fixation distractors. Results Nicotine reduced interference of incongruent distractors, but only under low-load conditions, where
Electronic supplementary material The online version of this article (doi:10.1007/s00213-014-3761-5) contains supplementary material, which is available to authorized users. O. Behler : T. P. K. Breckel : C. M. Thiel (*) Biological Psychology, Department of Psychology, European Medical School, Carl-von-Ossietzky Universität Oldenburg, Ammerländer Heer Str. 114-118, 26111 Oldenburg, Germany e-mail: [email protected] O. Behler Medical Physics, Department of Medical Physics and Acoustic, European Medical School, Carl-von-Ossietzky Universität Oldenburg, Oldenburg, Germany C. M. Thiel Cluster of Excellence “Hearing4all”, Carl von Ossietzky Universität Oldenburg, Oldenburg, Germany C. M. Thiel Research Center Neurosensory Science, Carl-von-Ossietzky Universität Oldenburg, Oldenburg, Germany
distractor effects were large. No effects of nicotine were observed under high-load conditions. Highly distractible subjects showed the largest effects of nicotine. Conclusions The findings suggest that nicotine acts primarily as a stimulus filter that prevents irrelevant stimuli from entering awareness in situations of high distractor interference. Keyword Nicotine . Attention . Psychopharmacology . Distraction . Perceptual load . Non-smoker . Drug . Acetylcholine
Introduction Numerous studies provide evidence that nicotine can improve cognitive performance in human smokers as well as in patients with attention deficit hyperactivity disorder (ADHD), schizophrenia and Parkinson’s and Alzheimer’s Diseases (Newhouse et al. 2004; Levin et al. 2006). In contrast, nicotine studies investigating healthy non-smokers have often yielded controversial or weak results (Foulds et al. 1996; Levin et al. 1998; Heishman and Henningfield 2000; Newhouse et al. 2004), supporting the notion that performance enhancements under nicotine might rather reflect a reversal of pathological or deprivation-induced deficits. In a recent meta-analysis of 40 studies in healthy non-smokers or minimally deprived smokers, however, Heishman et al. (2010) concluded that the beneficial effects of nicotine on attention are likely genuine and not confounded by withdrawal relief. Difficulties in finding significant results in non-smokers might arise from large interindividual differences in nicotine’s behavioural effects, which have been suggested to depend on “baseline characteristics” before drug exposure (Perkins 1999; Newhouse et al. 2004; Poltavski and Petros 2006; Giessing et al. 2007; Potter et al. 2012; Knott et al. 2013).
Psychopharmacology
Improvements of attentional functions under nicotine have been documented in many sustained and selective attention paradigms in smokers and non-smokers (e.g. Wesnes and Warburton 1984; Foulds et al. 1996; Mancuso et al. 1999; Lawrence et al. 2002; Trimmel and Wittberger 2004; Rycroft et al. 2005; Thiel et al. 2005; Meinke et al. 2006; Hahn et al. 2009) and are independent of smoking status (Trimmel and Wittberger 2004). The processes underlying these attentional improvements are, however, less clear. Kassel (1997) suggested that nicotine may enhance attentional processing by two different (not mutually exclusive) mechanisms, either by acting as a stimulus filter that prevents irrelevant stimuli from entering awareness or by enhancing the attentional focus to relevant stimuli via a boost in processing capacity. Most experimental approaches where subjects had to attend to relevant and ignore irrelevant stimuli did not intend to tease apart these two competing explanations but rather aimed at showing performance-enhancing effects of nicotine in the presence of distractors. These studies provide evidence that nicotine or specific α4β2 agonists alleviate the detrimental effects of distracting sensory stimuli in monkeys (Prendergast et al. 1998) and rodents (Hahn et al. 2002; Howe et al. 2010) performing visual tasks. There is also some evidence for reduced distraction in human smokers and non-smokers (Grobe et al. 1998; Trimmel and Wittberger 2004); see however Knott et al. (2006, 2009, 2011) for an absence of behavioural effects or Vangkilde et al. (2011) for increased distractibility. Hahn et al. (2002) suggested that the nicotine-induced distractor resistance may be mediated by an improved ability to focus attention on or, alternatively, to redirect attention back to task-relevant stimuli if it had been shifted towards the distractor. Nicotine’s well-documented ability to facilitate the reorienting of visuospatial attention after invalidly cueing the target location in visuospatial cueing tasks (Witte et al. 1997; Murphy and Klein 1998; Phillips et al. 2000; Thiel et al. 2005; Meinke et al. 2006; Thiel and Fink 2008; Vossel et al. 2008) conceivably supports the latter explanation. A recent electrophysiological study that investigated the effects of nicotine in a visual task with auditory distractors provides further evidence for a drug-induced improvement of re-focusing on taskrelevant stimuli after distraction, since amplitudes of the reorienting negativity were bigger under nicotine (Knott et al. 2011). The electrophysiological data under nicotine, however, also indicated significantly decreased amplitudes of the P3a component when compared to placebo (Knott et al. 2011; Mathalon et al. 2014). Because the P3a component is elicited by involuntary shifts of attention to task-irrelevant stimuli, this finding corroborates the idea that nicotine acts as a stimulus filter. To better differentiate between an improved ability to focus attention vs preventing involuntary shifts of attention to task-irrelevant stimuli, we investigated distractor interference in a visual search task with high and low
perceptual load (Lavie and Cox 1997; Beck and Lavie 2005). Studies using such tasks have repeatedly shown that distractor interference is reduced under high perceptual load when, according to the view of Lavie and colleagues, all available resources are exhausted. In contrast, under low perceptual load, spare capacity would spill over, resulting in perception of task-irrelevant stimuli. If nicotine acts primarily as a stimulus filter that prevents irrelevant stimuli entering awareness, one would predict that nicotine exerts its effects mainly in situations where irrelevant stimuli enter awareness easily, i.e. nicotine should reduce distractor processing under low-load conditions. If nicotine, however, heightens the attentional focus to relevant stimuli via a boost in processing capacity, one would predict that nicotine should have stronger effects in conditions where available capacities are exhausted, i.e. nicotine should increase available resources in high load conditions and hence increase distractor processing. Moreover, given the often reported baseline-dependent effects of nicotine mentioned above, we expected that behavioural effects of nicotine would depend on interindividual differences in baseline performance.
Methods Participants Thirty healthy non-smokers (13 males, 17 females; age range 18–35 years, mean and SD: 23.5±2.8 years), recruited at the University of Oldenburg, gave informed consent to participate in the study. A clinical evaluation was first carried out to ensure that participants had no conditions contraindicative for nicotine administration. Subjects were screened for major medical illness, including neurological and psychiatric disorders, history of alcohol and drug use and pregnancy. Ethics approval was obtained from the ethics committee of the German Psychological Association (DGPs). All procedures were performed in accordance with the Declaration of Helsinki (2008). Non-smokers were recruited to avoid confounding effects of nicotine abstinence on cognitive effects, that is, the possibility of reversing a deprivation-induced attentional deficit, rather than increasing attentional processes per se. Only volunteers who reported to have never been regular smokers were allowed to participate. All participants were right-handed (Oldfield, 1971; LQ>49), had normal, or corrected to normal, vision, no prior history of neurological or psychiatric disease and were free of medication except for contraceptives. Participants were asked to abstain from alcohol for 1 day before the experiment and from caffeine for at least 1 h prior to testing. One participant was excluded due to strong nausea following nicotine treatment and was subsequently replaced by a newly recruited subject.
Psychopharmacology
We used a within-subjects design. Each participant attended two experimental sessions, separated by at least 1 week. Drug administration was placebo-controlled and double blind and the order of pharmacological treatment was counterbalanced across subjects. Nicotine was delivered via a transdermal system (Niquitin® Clear 7 mg, GlaxoSmithKline Consumer Healthcare GmbH). A pharmacologically inactive, similar patch (Draco wound healing patch) served as placebo. Either patch was placed on the participants’ back right above the waist and was removed after 1 h, a few minutes before the start of the experimental task. Given a linear dose-concentration relationship of the delivery system, plasma levels achieved in the present study are expected to be about 3 ng/ml with a halflife of 3.2 h (Gorsline et al. 1992; Gorsline et al. 1993). Testing took place between 9 am and 5 pm. Placebo and nicotine sessions were always performed at the same time in each volunteer.
which alternated and had breaks of 30 s in between them. Each block consisted of 18 trials per distractor condition, yielding a total of 90 trials per block. Participants were asked to respond by pressing the left arrow key on a millisecond accurate keyboard with their right index finger if the target was an X, and by pressing the right arrow key with their right middle finger if the target was a Z. Both speed and accuracy were emphasized. Subjects were also instructed to ignore the distractors and were told that these were irrelevant to the task. Feedback was given in the form of either of two different tones - one for correct responses and the other for incorrect responses or the failure to respond within the maximum response time of 2 s. At the end of each experimental block, participants were additionally informed on the screen about their average reaction time (RT) and accuracy. The whole task was completed in approximately 30 min. In both sessions, participants completed a 5-min training session, consisting of 4 blocks with 20 trials each and alternating perceptual load conditions.
Stimuli and experimental paradigm
Statistical analysis of behavioural data
We employed a visual search task with high and low perceptual load and foveal distractors (Beck and Lavie 2005; Espeseth et al. 2010). The experiment took place in a darkened, sound-proof testing chamber. Stimuli were presented on a 19-in. monitor (DELL 1905FP) using the Cogent 2000 toolbox (Wellcome Department of imaging Neuroscience) for MATLAB (Version 7.1, The MathWorks Inc., Natick, MA, USA,). Viewing distance was approximately 60 cm. All stimuli were presented in light grey colour on a black background (see Fig. 1). Participants were instructed to maintain fixation on the centre of the screen, as indicated by a small cross, throughout the task. At the beginning of each trial, a circular array of six letters with a radius of 2° around the centre was presented for 100 ms. Target letters (X or Z) appeared randomly but with equal probability in one of the six positions. The other five positions were occupied by non-targets. In the low perceptual load condition, non-targets were always capital Os. In the high load condition, non-targets were capital A, H, K, N and Vs, arranged in random order with equal probability. In 80 % of the trials, the fixation cross was replaced by different task-irrelevant distractors. The distractor could either be congruent (e.g. X when the target was an X), incongruent (e.g. X when the target was a Z), neutral (a capital O) or physically salient (a black square). In 20 % of the trials, the fixation cross remained unchanged (“no distractor”/control condition). Targets, non-targets and distractors subtended 0.4°×0.5° of visual angle (except for the physically salient distractor, which subtended 0.5°×0.5° of visual angle). Following a time interval jittered around 3000 ms (±500 ms) after each stimulus presentation, the next trial began. Trials were arranged in three low-load blocks and three high-load blocks
Median RT and accuracy (correct responses/number of trials) were calculated for each participant as a function of drug (placebo, nicotine), load (low, high), and distractor condition (no distractor, congruent, incongruent, neutral, physically salient) and submitted to a repeated measures analysis of variance (ANOVA) with drug order (placebo-nicotine, nicotineplacebo) as between group factor. Significant interactions were further investigated by post hoc t tests. Incorrect responses were excluded from RT analyses. To investigate whether nicotine decreases distractor processing under low load and/or increases distractor processing under high load we focused on the difference between incongruent and no distractor trials only since distraction costs are highest with incongruent distractors. Two planned ANOVAs on the low and high load condition were performed which compared the distractor effect (ΔRT incongruent distractor, no distractor) under nicotine and placebo with drug order as between group factor. To investigate baseline-dependent effects of nicotine, we tested with a linear regression analysis whether the slope of the regression is significantly smaller than unity (see (Perkins 1999)).
Drug administration
Subjective and physiological measures To investigate side effects of the nicotine treatment, participants’ subjective mood and physical symptoms as well as heart rate and blood pressure were assessed three times in both sessions: Upon arrival (t1), immediately after removal of the placebo or nicotine patch (t2) and at the end of the experiment (t3). Subjective mood was assessed with visual analogue scales (Bond and Lader 1974). Rating scores were
Psychopharmacology Fig. 1 Illustration of the paradigm. Illustrated is the time course of two successive trials (e.g. a no distractor trial and an incongruent distractor trial) in the low- and high-load condition
grouped into the three factors “alertness”, “contentedness” and “calmness”, according to Bond and Lader (1974). Subjective physical symptoms (including headache, dizziness and nausea) were assessed with a customized checklist. At the end of each testing session, volunteers were asked to guess whether they received the nicotine or placebo patch. Mood scores, heart rate and blood pressure were submitted to a repeated measures ANOVA with drug (placebo, nicotine) and time (t1, t2, t3) as within-subjects factors.
Results Subjective and physiological measures Five subjects reported mild dizziness immediately after removal of the nicotine patch. These adverse effects, however, wore off towards the end of the session. Heart rates decreased over time (main effect of time F(2,58)=16.8, p
