Abstract
Nicotine has been shown to affect cortical excitability measured using transcranial magnetic stimulation in smoking and non-smoking subjects in different ways. In tobacco-deprived smokers, administration of nicotine restores compromised cortical facilitation while in non-smokers, it enhances cortical inhibition. As cortical excitability and activity are closely linked to cognitive processes, we aimed to explore whether nicotine-induced physiological alterations in non-smokers and smokers are associated with cognitive changes. Specifically, we assessed the impact of nicotine on working memory performance (n-back letter task) and on attentional processes (Stroop interference test) in healthy smokers and non-smokers. Both tasks have been shown to rely on prefrontal areas, and nicotinic receptors are relevantly involved in prefrontal function. Sixteen smoking and 16 non-smoking subjects participated in the 3-back letter task and 21 smoking and 21 non-smoking subjects in the Stroop test after the respective application of placebo or nicotine patches. The results show that working memory and attentional processes are compromised in nicotine-deprived smokers compared to non-smoking individuals. After administration of nicotine, working memory performance in smokers improved, while non-smoking subjects displayed decreased accuracy with increased number of errors. The effects have been shown to be more apparent for working memory performance than attentional processes. In summary, cognitive functions can be restored by nicotine in deprived smokers, whereas non-smokers do not gain additional benefit. The respective changes are in accordance with related effects of nicotine on cortical excitability in both groups.
Similar content being viewed by others
References
Adleman NE, Menon V, Blasey CM, White CD, Warsofsky IS, Glover GH, Reiss AL (2002) A developmental fMRI study of the Stroop color-word task. Neuroimage 16(1):61–75
Alkondon M, Braga MF, Pereira EF, Maelicke A, Albuquerque EX (2000) Alpha7 nicotinic acetylcholine receptors and modulation of gabaergic synaptic transmission in the hippocampus. Eur J Pharmacol 393(1–3):59–67
Ashare RL, Falcone M, Lerman C (2014) Cognitive function during nicotine withdrawal: implications for nicotine dependence treatment. Neuropharmacology 76(Pt B):581–591
Ashare RL, McKee SA (2012) Effects of varenicline and bupropion on cognitive processes among nicotine-deprived smokers. Exp Clin Psychopharmacol 20(1):63–70
Assef EC, Capovilla AG, Capovilla FC (2007) Computerized stroop test to assess selective attention in children with attention deficit hyperactivity disorder. Span J Psychol 10(1):33–40
Atzori G, Lemmonds CA, Kotler ML, Durcan MJ, Boyle J (2008) Efficacy of a nicotine (4 mg)-containing lozenge on the cognitive impairment of nicotine withdrawal. J Clin Psychopharmacol 28(6):667–674
Azizian A, Nestor LJ, Payer D, Monterosso JR, Brody AL, London ED (2010) Smoking reduces conflict-related anterior cingulate activity in abstinent cigarette smokers performing a Stroop task. Neuropsychopharmacology 35(3):775–782
Baddeley A (1992) Working memory. Science 255(5044):556–559, Review
Barone JA (1999) Domperidone: a peripherally acting dopamine2-receptor antagonist. Ann Pharmacother 33(4):429–440, Review
Barr RS, Culhane MA, Jubelt LE, Mufti RS, Dyer MA, Weiss AP et al (2008) The effects of transdermal nicotine on cognition in nonsmokers with schizophrenia and nonpsychiatric controls. Neuropsychopharmacology 33(3):480–490
Brehmer Y, Westerberg H, Bäckman L (2012) Working-memory training in younger and older adults: training gains, transfer, and maintenance. Front Hum Neurosci 6:63
Brunoni AR, Vanderhasselt MA (2014) Working memory improvement with non-invasive brain stimulation of the dorsolateral prefrontal cortex: a systematic review and meta-analysis. Brain Cogn 86:1–9
Bryan J, Luszcz MA (2000) Measures of fluency as predictors of incidental memory among older adults. Psychol Aging 15(3):483–489
Driesen NR, McCarthy G, Bhagwagar Z, Bloch MH, Calhoun VD, D'Souza DC et al (2013) The impact of NMDA receptor blockade on human working memory-related prefrontal function and connectivity. Neuropsychopharmacology 38(13):2613–2622
Ernst M, Matochik JA, Heishman SJ, Van Horn JD, Jons PH, Henningfield JE et al (2001) Effect of nicotine on brain activation during performance of a working memory task. Proc Natl Acad Sci 98(8):4728–4733
Evans DE, Drobes DJ (2009) Nicotine self-medication of cognitive-attentional processing. Addict Biol 14(1):32–42
Foulds J, Stapleton J, Swettenham J, Bell N, McSorley K, Russell MA (1996) Cognitive performance effects of subcutaneous nicotine in smokers and never-smokers. Psychopharmacol (Berl) 127(1):31–38
Fresnoza S, Paulus W, Nitsche MA, Kuo MF (2014) Nonlinear dose-dependent impact of D1 receptor activation on motor cortex plasticity in humans. J Neurosci 34(7):2744–2753
Greenstein JE, Kassel JD (2009) The effects of smoking and smoking abstinence on verbal and visuospatial working memory capacity. Exp Clin Psychopharmacol 17(2):78–90
Grundey J, Freznosa S, Klinker F, Lang N, Paulus W, Nitsche MA (2013) Cortical excitability in smoking and not smoking individuals with and without nicotine. Psychopharmacol (Berl) 229(4):653–664
Haatveit BC, Sundet K, Hugdahl K, Ueland T, Melle I, Andreassen OA (2010) The validity of d prime as a working memory index: results from the "Bergen n-back task". J Clin Exp Neuropsychol 32(8):871–880
Holmes AD, Chenery HJ, Copland DA (2008) Transdermal nicotine modulates strategy-based attentional semantic processing in non-smokers. Int J Neuropsychopharmacol 11(3):389–399
Jacobsen LK, Mencl WE, Constable RT, Westerveld M, Pugh KR (2007) Impact of smoking abstinence on working memory neurocircuitry in adolescent daily tobacco smokers. Psychopharmacol (Berl) 193(4):557–566
Jensen AR, Rohwer WD Jr (1966) Stroop color-word test: a review. Acta Psychol (Amst) 25(1):36–93, Review. No abstract available
Jeon SY, Han SJ (2012) Improvement of the working memory and naming by transcranial direct current stimulation. Ann Rehabil Med 36(5):585–595
Klein E, Mann A, Huber S, Bloechle J, Willmes K, Karim AA et al (2013) Bilateral bi-cephalic tDCS with two active electrodes of the same polarity modulates bilateral cognitive processes differentially. PLoS One 8:8(8)
Kumari V, Gray JA, ffytche DH, Mitterschiffthaler MT, Das M, Zachariah E et al (2003) Cognitive effects of nicotine in humans: an fMRI study. Neuroimage 19(3):1002–1013
Lang N, Hasan A, Sueske E, Paulus W, Nitsche MA (2008) Cortical hypoexcitability in chronic smokers? A transcranial magnetic stimulation study. Neuropsychopharmacology 33(10):2517–2523
Lawrence NS, Ross TJ, Stein EA (2002) Cognitive mechanisms of nicotine on visual attention. Neuron 36(3):539–548
Li X, Semenova S, D'Souza MS, Stoker AK (2014) Markou A (2014): Involvement of glutamatergic and GABAergic systems in nicotine dependence: implications for novel pharmacotherapies for smoking cessation. Neuropharmacology 554–65
Loughead J, Wileyto EP, Valdez JN, Sanborn P, Tang K, Strasser AA, Ruparel K, Ray R, Gur RC, Lerman C (2009) Effect of abstinence challenge on brain function and cognition in smokers differs by COMT genotype. Mol Psychiatry 14(8):820–826
Martin DM, Liu R, Alonzo A, Green M, Loo CK (2014) Use of transcranial direct current stimulation (tDCS) to enhance cognitive training: effect of timing of stimulation. Exp Brain Res 232(10):3345–3351
Macmillan NA, Creelman CD (1991) Detection theory: a user’s guide. Cambridge University Press, Cambridge
Meinke A, Thiel CM, Fink GR (2006) Effects of nicotine on visuo-spatial selective attention as indexed by event-related potentials. Neuroscience 141(1):201–212
Miniussi C, Ruzzoli M (2013) Handb Clin Neurol 116:739–750
Monte-Silva K, Liebetanz D, Grundey J, Paulus W, Nitsche MA (2011) Dosage-dependent non-linear effect of L-dopa on human motor cortex plasticity. J Physiol 588(Pt 18):3415–3424
Mull BR, Seyal M (2001) Transcranial magnetic stimulation of left prefrontal cortex impairs working memory. Clin Neurophysiol 112:1672–1675
Nørregaard J, Tønnesen P, Simonsen K, Säwe U (1992) Long-term nicotine substitution after application of a 16-hour nicotine patch in smoking cessation. Eur J Clin Pharmacol 43(1):57–60
Peña-Casanova J, Quiñones-Ubeda S, Gramunt-Fombuena N, Quintana M, Aguilar M, Molinuevo JL et al (2009) NEURONORMA Study Team. Spanish Multicenter Normative Studies (NEURONORMA Project): norms for the Stroop color-word interference test and the Tower of London-Drexel. Arch Clin Neuropsychol 24(4):413–429
Pomerleau CS, Teuscher F, Goeters S, Pomerleau OF (1994) Effects of nicotine abstinence and menstrual phase on task performance. Addict Behav 19(4):357–362
Poorthuis RB, Mansvelder HD (2013) Nicotinic acetylcholine receptors controlling attention: behavior, circuits and sensitivity to disruption by nicotine. Biochem Pharmacol 86(8):1089–1098
Snyder FR, Henningfield JE (1989) Effects of nicotine administration following 12 h of tobacco deprivation: assessment on computerized performance tasks. Psychopharmacol (Berl) 97(1):17–22
Spirt MJ, Chan W, Thieberg M, Sachar DB (1992) Neurolepticmalignant syndrome induced by domperidone. Dig Dis Sci 37(6):946–948
Stackman RW, Walsh TJ (1994) Baclofen produces dose-related working memory impairments after intraseptal injection. Behav Neural Biol 61(2):181–185
Thirugnanasambandam N, Grundey J, Adam K, Drees A, Skwirba AC, Lang N et al (2011) Nicotinergic impact on focal and non-focal neuroplasticity induced by non-invasive brain stimulation in non-smoking humans. Neuropsychopharmacology 36(4):879–886
Tønnesen P, Nørregaard J, Simonsen K, Säwe U (1991) A double-blind trial of a 16-hour transdermal nicotine patch in smoking cessation. N Engl J Med 325(5):311–315
Wagner M, Schulze-Rauschenbach S, Petrovsky N, Brinkmeyer J, von der Goltz C, Gründer G, Spreckelmeyer KN et al (2013) Neurocognitive impairments in non-deprived smokers—results from a population-based multi-center study on smoking-related behavior. Addict Biol 18(4):752–761
White HK, Levin ED (1999) Four-week nicotine skin patch treatment effects on cognitive performance in Alzheimer's disease. Psychopharmacol (Berl) 143(2):158–165
Wignall ND, de Wit H (2011) Effects of nicotine on attention and inhibitory control in healthy nonsmokers. Exp Clin Psychopharmacol 19(3):183–191
Wilson AL, Langley LK, Monley J, Bauer T, Rottunda S, McFalls E et al (1995) Nicotine patches in Alzheimer's disease: pilot study on learning, memory, and safety. Pharmacol Biochem Behav 51(2–3):509–514
Ziemann U, Chen R, Cohen LG, Hallett M (1998) Dextromethorphan decreases the excitability of the human motor cortex. Neurology 51(5):1320–1324
Acknowledgments
This study was supported by the Deutsche Forschungsgemeinschaft (DFG grant NI 683/4-1) ‘Towards risk prediction of nicotine dependency by exploring individual limits of cortical neuroplasticity in humans’ and ‘Impact of the nicotinergic alpha7 receptor on cortical plasticity in smokers and non-smokers’ (NI683/4-2) within the DFG priority program ‘Nicotine: Molecular and Physiological Effects in Central Nervous System’.
Conflict of interest
JG, RA, GA, and GB received no financial support, and no compensation has been received from any individual or corporate entity over the past 3 years for research or professional service, and there are no personal financial holdings that could be perceived as constituting a potential conflict of interest. WP is member of the Advisory Boards of GSK, UCB, Desitin. MAN is member of the Advisory Boards of UCB, Eisai, GSK, and Neuroelectronics.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Grundey, J., Amu, R., Ambrus, G.G. et al. Double dissociation of working memory and attentional processes in smokers and non-smokers with and without nicotine. Psychopharmacology 232, 2491–2501 (2015). https://doi.org/10.1007/s00213-015-3880-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00213-015-3880-7