Abstract
Rationale
The non-selective nicotinic acetylcholine receptor (nAChR) agonist nicotine has been argued to improve attention via enhanced filtering of irrelevant stimuli. Here, we tested this hypothesis in the context of smooth pursuit eye movements (SPEMs), an oculomotor function previously shown to improve with nicotine in some but not all studies.
Objectives
In order to test whether nicotine improves performance particularly when the inhibition of distracting stimuli is required, SPEM was elicited in conditions with or without peripheral distractors. Additionally, different target frequencies were employed in order to parametrically vary general processing demands on the SPEM system.
Methods
Healthy adult non-smokers (N = 18 females, N = 13 males) completed a horizontal sinusoidal SPEM task at different target frequencies (0.2 Hz, 0.4 Hz, 0.6 Hz) in the presence or absence of peripheral distractors in a double-blind, placebo-controlled, cross-over design using a 2 mg nicotine gum.
Results
Nicotine increased peak pursuit gain relative to placebo (p < .001), but an interaction with distractor condition (p = .001) indicated that this effect was most pronounced in the presence of distractors. Catch-up saccade frequency was reduced by nicotine (p = .01), particularly at higher target frequencies (two-way interaction, p = .04). However, a three-way interaction (p = .006) indicated that the reduction with nicotine was strongest at the highest target frequency (0.6 Hz) only without distractors, whereas in the presence of distractors, it was strongest at 0.4-Hz target frequency. There were no effects of nicotine on subjective state measures.
Conclusions
Together, these findings support a role of both distractor inhibition and general processing load in the effects of nicotine on smooth pursuit.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Notes
A sinusoidal target waveform refers to the changing pattern of target velocity over time, which reflects a smooth periodic oscillation horizontally across the screen.
In agreement with the wider SPEM literature, the continuously changing velocity of a sinusoidal target is given here in Hertz (Hz).
References
Avila MT, Sherr JD, Hong E, Myers CS, Thaker GK (2003) Effects of nicotine on leading saccades during smooth pursuit eye movements in smokers and nonsmokers with schizophrenia. Neuropsychopharmacology 28:2184–2191. https://doi.org/10.1038/sj.npp.1300265
Barnes GR (2008) Cognitive processes involved in smooth pursuit eye movements. Brain Cogn 68:309–326. https://doi.org/10.1016/j.bandc.2008.08.020
Behler O, Breckel TPK, Thiel CM (2015) Nicotine reduces distraction under low perceptual load. Psychopharmacology 232:1269–1277. https://doi.org/10.1007/s00213-014-3761-5
Bond A, Lader M (1974) The use of analogue scales in rating subjective feelings. Br J Med Psychol 47:211–218. https://doi.org/10.1111/j.2044-8341.1974.tb02285.x
Chun CA, Minor KS, Cohen AS (2013) Neurocognition in psychometrically defined college schizotypy samples: we are not measuring the “right stuff.”. J Int Neuropsychol Soc 19:324–337. https://doi.org/10.1017/S135561771200152X
Clementz BA, Sweeney JA, Hirt M, Haas G (1990) Pursuit gain and saccadic intrusions in first-degree relatives of probands with schizophrenia. J Abnorm Psychol 99:327–335
Cohen J (1973) Eta-squared and partial eta-squared in fixed factor ANOVA designs. Educ Psychol Meas 33:107–112. https://doi.org/10.1177/001316447303300111
Cohen AS, Auster TL, MacAulay RK, McGovern JE (2014) The paradox of schizotypy: resemblance to prolonged severe mental illness in subjective but not objective quality of life. Psychiatry Res 217:185–190. https://doi.org/10.1016/j.psychres.2014.03.016
Collewijn H, Tamminga EP (1984) Human smooth and saccadic eye movements during voluntary pursuit of different target motions on different backgrounds. J Physiol 351:217–250
Costa A, Riedel M, Pogarell O, Menzel-Zelnitschek F, Schwarz M, Reiser M, Möller HJ, Rubia K, Meindl T, Ettinger U (2013) Methylphenidate effects on neural activity during response inhibition in healthy humans. Cereb Cortex 23:1179–1189. https://doi.org/10.1093/cercor/bhs107
Dépatie L, O’Driscoll GA, Holahan A-LV et al (2002) Nicotine and behavioral markers of risk for schizophrenia: a double-blind, placebo-controlled, cross-over study. Neuropsychopharmacology 27:1056–1070. https://doi.org/10.1016/S0893-133X(02)00372-X
Domino EF, Ni LS, Zhang H (1997) Effects of tobacco smoking on human ocular smooth pursuit. Clin Pharmacol Ther 61:349–359. https://doi.org/10.1016/S0009-9236(97)90168-5
Ettinger U, Kumari V (2003) Pharmacological studies of smooth pursuit and antisaccade eye movements in schizophrenia: current status and directions for future research. Curr Neuropharmacol 1:285–300
Ettinger U, Kumari V (2018) Effects of nicotine on inhibitory control in humans. In: Preedy V (ed) The neuroscience of nicotine: mechanisms and treatment. Elsevier, Amsterdam
Ettinger U, Williams SCR, Patel D, Michel TM, Nwaigwe A, Caceres A, Mehta MA, Anilkumar AP, Kumari V (2009) Effects of acute nicotine on brain function in healthy smokers and non-smokers: estimation of inter-individual response heterogeneity. Neuroimage 45:549–561. https://doi.org/10.1016/j.neuroimage.2008.12.029
Ettinger U, Faiola E, Kasparbauer A-M, Petrovsky N, Chan RCK, Liepelt R, Kumari V (2017) Effects of nicotine on response inhibition and interference control. Psychopharmacology 234:1093–1111. https://doi.org/10.1007/s00213-017-4542-8
Fedota JR, Stein EA (2015) Resting-state functional connectivity and nicotine addiction: prospects for biomarker development. Ann N Y Acad Sci 1349:64–82. https://doi.org/10.1111/nyas.12882
Giessing C, Thiel CM (2012) Pro-cognitive drug effects modulate functional brain network organization. Front Behav Neurosci 6:53. https://doi.org/10.3389/fnbeh.2012.00053
Glass GV (1966) Testing homogeneity of variances. Am Educ Res J 3:187–190. https://doi.org/10.3102/00028312003003187
Grobe JE, Perkins KA, Goettler-Good J, Wilson A (1998) Importance of environmental distractors in the effects of nicotine on short-term memory. Exp Clin Psychopharmacol 6:209–216
Hahn B (2015) Nicotinic receptors and attention. Curr Top Behav Neurosci 23:103–135. https://doi.org/10.1007/978-3-319-13665-3_5
Haraldsson HM, Ettinger U, Magnusdottir BB, Sigmundsson T, Sigurdsson E, Petursson H (2008) Eye movement deficits in schizophrenia: investigation of a genetically homogenous Icelandic sample. Eur Arch Psychiatry Clin Neurosci 258:373–383. https://doi.org/10.1007/s00406-008-0806-y
Heishman SJ, Kleykamp BA, Singleton EG (2010) Meta-analysis of the acute effects of nicotine and smoking on human performance. Psychopharmacology 210:453–469. https://doi.org/10.1007/s00213-010-1848-1
Hutton SB, Crawford TJ, Kennard C, Barnes TR, Joyce EM (2000) Smooth pursuit eye tracking over a structured background in first-episode schizophrenic patients. Eur Arch Psychiatry Clin Neurosci. 250(5):221–5
Hutton SB, Tegally D (2005) The effects of dividing attention on smooth pursuit eye tracking. Exp Brain Res 163:306–313. https://doi.org/10.1007/s00221-004-2171-z
Iacono WG, Tuason VB, Johnson RA (1981) Dissociation of smooth-pursuit and saccadic eye tracking in remitted schizophrenics. An ocular reaction time task that schizophrenic perform well. Arch Gen Psychiatry 38:991–996
Jasinska AJ, Zorick T, Brody AL, Stein EA (2014) Dual role of nicotine in addiction and cognition: a review of neuroimaging studies in humans. Neuropharmacology 84:111–122. https://doi.org/10.1016/j.neuropharm.2013.02.015
Jennings JR (1987) Editorial policy on analyses of variance with repeated measures. Psychophysiology 24:474–475. https://doi.org/10.1111/j.1469-8986.1987.tb00320.x
Kalman D (2002) The subjective effects of nicotine: methodological issues, a review of experimental studies, and recommendations for future research. Nicotine Tob Res 4:25–70
Kalman D, Smith SS (2005) Does nicotine do what we think it does? A meta-analytic review of the subjective effects of nicotine in nasal spray and intravenous studies with smokers and nonsmokers. Nicotine Tob Res 7:317–333
Kamkwalala AR, Newhouse PA (2017) Beyond acetylcholinesterase inhibitors: novel cholinergic treatments for Alzheimer’s disease. Curr Alzheimer Res 14:377–392. https://doi.org/10.2174/1567205013666160930112625
Kasparbauer A-M, Meyhöfer I, Steffens M, Weber B, Aydin M, Kumari V, Hurlemann R, Ettinger U (2016) Neural effects of methylphenidate and nicotine during smooth pursuit eye movements. Neuroimage 141:52–59. https://doi.org/10.1016/j.neuroimage.2016.07.012
Kasparbauer A-M, Petrovsky N, Schmidt P-M, Trautner P, Weber B, Sträter B, Ettinger U (2019) Effects of nicotine and atomoxetine on brain function during response inhibition. Eur Neuropsychopharmacol 29:235–246. https://doi.org/10.1016/j.euroneuro.2018.12.004
Kassel JD (1997) Smoking and attention: a review and reformulation of the stimulus-filter hypothesis. Clin Psychol Rev 17:451–478
Kathmann N, Hochrein A, Uwer R (1999) Effects of dual task demands on the accuracy of smooth pursuit eye movements. Psychophysiology 36:158–163
Klein C, Andresen B (1991) On the influence of smoking upon smooth pursuit eye movements of schizophrenics and normal controls. J Psychophysiol 5:361–369
Knott V, Shah D, Fisher D, Millar A, Prise S, Scott TL, Thompson M (2009) Nicotine and attention: event-related potential investigations in nonsmokers. Clin EEG Neurosci 40:11–20. https://doi.org/10.1177/155005940904000108
Knott V, Heenan A, Shah D, Bolton K, Fisher D, Villeneuve C (2011) Electrophysiological evidence of nicotine’s distracter-filtering properties in non-smokers. J Psychopharmacol 25:239–248. https://doi.org/10.1177/0269881109348158
Kumari V, Postma P (2005) Nicotine use in schizophrenia: the self medication hypotheses. Neurosci Biobehav Rev 29:1021–1034. https://doi.org/10.1016/j.neubiorev.2005.02.006
Kumari V, Cotter PA, Checkley SA, Gray JA (1997) Effect of acute subcutaneous nicotine on prepulse inhibition of the acoustic startle reflex in healthy male non-smokers. Psychopharmacology 132:389–395
Kumari V, Soni W, Sharma T (2001) Influence of cigarette smoking on prepulse inhibition of the acoustic startle response in schizophrenia. Hum Psychopharmacol Clin Exp 16:321–326. https://doi.org/10.1002/hup.286
Lehrl S (2005) Mehrfachwahl-Wortschatz-Intelligenztest MWT-B. Spitta GmbH, Balingen
Lehrl S, Triebig G, Fischer B (1995) Multiple choice vocabulary test MWT as a valid and short test to estimate premorbid intelligence. Acta Neurol Scand 91:335–345
Leigh RJ, Zee DS (2015) The neurology of eye movements. Oxford University Press, New York
Lencer R, Trillenberg P (2008) Neurophysiology and neuroanatomy of smooth pursuit in humans. Brain Cogn 68:219–228. https://doi.org/10.1016/j.bandc.2008.08.013
Levin ED, Rezvani AH (2002) Nicotinic treatment for cognitive dysfunction. Curr Drug Targets CNS Neurol Disord 1:423–431
Levin ED, Conners CK, Sparrow E, Hinton SC, Erhardt D, Meck WH, Rose JE, March J (1996) Nicotine effects on adults with attention-deficit/hyperactivity disorder. Psychopharmacology 123:55–63. https://doi.org/10.1007/BF02246281
Levy DL, Sereno AB, Gooding DC, O’Driscoll GA (2010) Eye tracking dysfunction in schizophrenia: characterization and pathophysiology. Curr Top Behav Neurosci 4:311–347. https://doi.org/10.1007/7854_2010_60
Lisberger SG, Ferrera VP (1997) Vector averaging for smooth pursuit eye movements initiated by two moving targets in monkeys. J Neurosci 17:7490–7502
Lisberger SG, Morris EJ, Tychsen L (1987) Visual motion processing and sensory-motor integration for smooth pursuit eye movements. Annu Rev Neurosci 10:97–129. https://doi.org/10.1146/annurev.ne.10.030187.000525
Mesulam MM (2013) Cholinergic circuitry of the human nucleus basalis and its fate in Alzheimer’s disease. J Comp Neurol 521:4124–4144
Meyhöfer I, Steffens M, Kasparbauer A, Grant P, Weber B, Ettinger U (2015) Neural mechanisms of smooth pursuit eye movements in schizotypy. Hum Brain Mapp 36:340–353. https://doi.org/10.1002/hbm.22632
Nees F (2015) The nicotinic cholinergic system function in the human brain. Neuropharmacology 96:289–301. https://doi.org/10.1016/j.neuropharm.2014.10.021
Newhouse PA, Potter AS, Dumas JA, Thiel CM (2011) Functional brain imaging of nicotinic effects on higher cognitive processes. Biochem Pharmacol 82:943–951. https://doi.org/10.1016/j.bcp.2011.06.008
Norris H (1971) The action of sedatives on brain stem oculomotor systems in man. Neuropharmacology. 10:181–191. https://doi.org/10.1016/0028-3908(71)90039-6
O’Driscoll GA, Callahan BL (2008) Smooth pursuit in schizophrenia: a meta-analytic review of research since 1993. Brain Cogn 68:359–370. https://doi.org/10.1016/j.bandc.2008.08.023
Oldfield RC (1971) The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 9:97–113. https://doi.org/10.1016/0028-3932(71)90067-4
Olincy A, Ross RG, Young DA, Roath M, Freedman R (1998) Improvement in smooth pursuit eye movements after cigarette smoking in schizophrenic patients. Neuropsychopharmacology 18:175–185. https://doi.org/10.1016/S0893-133X(97)00095-X
Olincy A, Johnson LL, Ross RG (2003) Differential effects of cigarette smoking on performance of a smooth pursuit and a saccadic eye movement task in schizophrenia. Psychiatry Res 117:223–236
Poorthuis RB, Mansvelder HD (2013) Nicotinic acetylcholine receptors controlling attention: behavior, circuits and sensitivity to disruption by nicotine. Biochem Pharmacol 86:1089–1098. https://doi.org/10.1016/j.bcp.2013.07.003
Provost SC, Woodward R (1991) Effects of nicotine gum on repeated administration of the Stroop test. Psychopharmacology 104:536–540
Reilly JL, Lencer R, Bishop JR, Keedy S, Sweeney JA (2008) Pharmacological treatment effects on eye movement control. Brain Cogn 68:415–435. https://doi.org/10.1016/j.bandc.2008.08.026
Ross RG, Olincy A, Zerbe G, Radant A (2001) Which duration of postsaccadic slowing identifies anticipatory saccades during smooth pursuit eye movements? Psychophysiology 38:325–333
Ross RG, Olincy A, Mikulich SK, Radant AD, Harris JG, Waldo M, Compagnon N, Heinlein S, Leonard S, Zerbe GO, Adler L, Freedman R (2002) Admixture analysis of smooth pursuit eye movements in probands with schizophrenia and their relatives suggests gain and leading saccades are potential endophenotypes. Psychophysiology 39:809–819. https://doi.org/10.1017/S0048577202011691
Sacco KA, Bannon KL, George TP (2004) Nicotinic receptor mechanisms and cognition in normal states and neuropsychiatric disorders. J Psychopharmacol 18:457–474. https://doi.org/10.1177/026988110401800403
Schlenker R, Cohen R, Berg P, Hubman W, Mohr F, Watzl H, Werther P (1994) Smooth-pursuit eye movement dysfunction in schizophrenia: the role of attention and general psychomotor dysfunctions. Eur Arch Psychiatry Clin Neurosci 244:153–160
Schmechtig A, Lees J, Grayson L, Craig KJ, Dadhiwala R, Dawson GR, Deakin JFW, Dourish CT, Koychev I, McMullen K, Migo EM, Perry C, Wilkinson L, Morris R, Williams SCR, Ettinger U (2013) Effects of risperidone, amisulpride and nicotine on eye movement control and their modulation by schizotypy. Psychopharmacology 227:331–345. https://doi.org/10.1007/s00213-013-2973-4
Sheehan DV, Lecrubier Y, Sheehan KH et al (1998) The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 59:22–33
Sherr JD, Myers C, Avila MT, Elliott A, Blaxton TA, Thaker GK (2002) The effects of nicotine on specific eye tracking measures in schizophrenia. Biol Psychiatry 52:721–728
Sibony PA, Evinger C, Manning KA (1988) The effects of tobacco smoking on smooth pursuit eye movements. Ann Neurol 23:238–241. https://doi.org/10.1002/ana.410230305
Singh A, Potter A, Newhouse P (2004) Nicotinic acetylcholine receptor system and neuropsychiatric disorders. IDrugs 7:1096–1103
Smucny J, Olincy A, Eichman LS, Tregellas JR (2015) Neuronal effects of nicotine during auditory selective attention. Psychopharmacology 232:2017–2028. https://doi.org/10.1007/s00213-014-3832-7
Smyrnis N (2008) Metric issues in the study of eye movements in psychiatry. Brain Cogn 68:341–358. https://doi.org/10.1016/j.bandc.2008.08.022
Steffens M, Becker B, Neumann C, Kasparbauer AM, Meyhöfer I, Weber B, Mehta MA, Hurlemann R, Ettinger U (2016) Effects of ketamine on brain function during smooth pursuit eye movements. Hum Brain Mapp 37:4047–4060. https://doi.org/10.1002/hbm.23294
Tanabe J, Tregellas JR, Martin LF, Freedman R (2006) Effects of nicotine on hippocampal and cingulate activity during smooth pursuit eye movement in schizophrenia. Biol Psychiatry 59:754–761. https://doi.org/10.1016/j.biopsych.2005.09.004
Thaker GK, Ellsberry R, Moran M, Lahti A, Tamminga C (1991) Tobacco smoking increases square-wave jerks during pursuit eye movements. Biol Psychiatry 29:82–88
Thiel CM, Zilles K, Fink GR (2005) Nicotine modulates reorienting of visuospatial attention and neural activity in human parietal cortex. Neuropsychopharmacology 30:810–820. https://doi.org/10.1038/sj.npp.1300633
Tregellas JR, Tanabe JL, Martin LF, Freedman R (2005) fMRI of response to nicotine during a smooth pursuit eye movement task in schizophrenia. Am J Psychiatry 162:391–393. https://doi.org/10.1176/appi.ajp.162.2.391
Tregellas JR, Olincy A, Johnson L, Tanabe J, Shatti S, Martin LF, Singel D, du YP, Soti F, Kem WR, Freedman R (2010) Functional magnetic resonance imaging of effects of a nicotinic agonist in schizophrenia. Neuropsychopharmacology 35:938–942. https://doi.org/10.1038/npp.2009.196
Van Donkelaar P, Drew AS (2002) The allocation of attention during smooth pursuit eye movements. Prog Brain Res 140:267–277. https://doi.org/10.1016/S0079-6123(02)40056-8
Acknowledgments
We are grateful to the Nicotine Science Center at Fertin Pharma A/S for providing the nicotine and placebo gums. We would like to thank Felix Benninghoff-Lühl, Christina Esser, Adrian Pick and Carina Steinberg for their excellent support in data collection.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Approval of the local ethics committee was obtained and the study was conducted in agreement with the latest version of the Code of Ethics of the World Medical Association (Declaration of Helsinki).
Conflict of interest
The authors declare that they have no conflicts of interest.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
ESM 1
(DOCX 82 kb)
Rights and permissions
About this article
Cite this article
Meyhöfer, I., Kasparbauer, AM., Steffens, M. et al. Effects of nicotine on smooth pursuit eye movements in healthy non-smokers. Psychopharmacology 236, 2259–2271 (2019). https://doi.org/10.1007/s00213-019-05223-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00213-019-05223-1