Advertisement

Psychopharmacology

, Volume 213, Issue 1, pp 29–42 | Cite as

Chronic smoking, but not acute nicotine administration, modulates neural correlates of working memory

  • Matthew T. SutherlandEmail author
  • Thomas J. Ross
  • Diaá M. Shakleya
  • Marilyn A. Huestis
  • Elliot A. Stein
Original Investigation

Abstract

Rationale

Beyond the amelioration of deprivation-induced impairments, and in contrast to effects on attentional processes, the cognitive-enhancing properties of nicotine on working memory (WM) operations remain unclear.

Objectives

In an effort to elucidate potential enhancing effects, we explored the impact of transdermal nicotine on neural functioning in minimally deprived smokers and, in addition, assessed differences between smokers and non-smokers using a mixed block/event-related fMRI design that attempted to isolate specific central executive operations (attentional switch events) within general WM function (task blocks).

Methods

In task blocks, participants performed a continuous counting paradigm that required the simultaneous maintenance of, and frequent switching of attentional focus between, two running tallies in WM on some trials. Cigarette smokers (n = 30) were scanned twice, once each with a nicotine and placebo patch, while non-smokers (n = 27) were scanned twice with no patch.

Results

Across both groups, task blocks were associated with bilateral activation, notably in medial and lateral prefrontal cortex (PFC), anterior insula, and parietal regions, whereas individual attentional switch trials were associated with activation in a similar, but predominantly left-lateralized network. Within the smoker group, although nicotine increased heart rate, altered performance and mood, and reduced tobacco cravings, no acute drug (state-like) effect on brain activity was detected for either the task or switch effects. However, relative to non-smokers, smokers showed greater tonic activation in medial superior frontal cortex, right anterior insula, and bilateral anterior PFC throughout task blocks (trait-like effect).

Conclusions

These data suggest smokers require recruitment of additional WM and supervisory control operations during task performance.

Keywords

Nicotine Central executive Working memory Anterior prefrontal cortex Medial superior frontal cortex Anterior insula 

Notes

Acknowledgments

This work was supported by the National Institute on Drug Abuse—Intramural Research Program. We thank all NIDA-IRP staff members who assisted in data collection, the NIH Fellow’s Editorial Board for suggestions on this manuscript, and Hugh Garavan.

Conflict of interest

The authors declare no conflicts of interest.

Supplementary material

213_2010_2013_MOESM1_ESM.doc (1.8 mb)
ESM 1 (DOC 1874 kb)

References

  1. Baddeley A (2000) The episodic buffer: a new component of working memory? Trends Cogn Sci 4:417–423CrossRefPubMedGoogle Scholar
  2. Baddeley A (2003) Working memory: looking back and looking forward. Nat Rev Neurosci 4:829–839CrossRefPubMedGoogle Scholar
  3. Baddeley A, Hitch G (1974) Working memory. In: Bower GA (ed) The psychology of learning and motivation. Academic, New York, pp 47–89Google Scholar
  4. Barr RS, Culhane MA, Jubelt LE, Mufti RS, Dyer MA, Weiss AP, Deckersbach T, Kelly JF, Freudenreich O, Goff DC, Evins AE (2008) The effects of transdermal nicotine on cognition in nonsmokers with schizophrenia and nonpsychiatric controls. Neuropsychopharmacology 33:480–490CrossRefPubMedGoogle Scholar
  5. Bonson KR, Grant SJ, Contoreggi CS, Links JM, Metcalfe J, Weyl HL, Kurian V, Ernst M, London ED (2002) Neural systems and cue-induced cocaine craving. Neuropsychopharmacology 26:376–386CrossRefPubMedGoogle Scholar
  6. Braver TS, Reynolds JR, Donaldson DI (2003) Neural mechanisms of transient and sustained cognitive control during task switching. Neuron 39:713–726CrossRefPubMedGoogle Scholar
  7. Brody AL, Mandelkern MA, London ED, Childress AR, Lee GS, Bota RG, Ho ML, Saxena S, Baxter LR, Madsen D, Jarvik ME (2002) Brain metabolic changes during cigarette craving. Arch Gen Psychiatry 59:1162–1172CrossRefPubMedGoogle Scholar
  8. Brody AL, Mandelkern MA, Jarvik ME, Lee GS, Smith EC, Huang JC, Bota RG, Bartzokis G, London ED (2004) Differences between smokers and nonsmokers in regional gray matter volumes and densities. Biol Psychiatry 55:77–84CrossRefPubMedGoogle Scholar
  9. Buckner RL, Andrews-Hanna JR, Schacter DL (2008) The brain’s default network: anatomy, function, and relevance to disease. Ann N Y Acad Sci 1124:1–38CrossRefPubMedGoogle Scholar
  10. Buracas GT, Boynton GM (2002) Efficient design of event-related fMRI experiments using M-sequences. Neuroimage 16:801–813CrossRefPubMedGoogle Scholar
  11. Cabeza R, Nyberg L (2000) Imaging cognition II: an empirical review of 275 PET and fMRI studies. J Cogn Neurosci 12:1–47CrossRefPubMedGoogle Scholar
  12. Cabeza R, Daselaar SM, Dolcos F, Prince SE, Budde M, Nyberg L (2004) Task-independent and task-specific age effects on brain activity during working memory, visual attention and episodic retrieval. Cereb Cortex 14:364–375CrossRefPubMedGoogle Scholar
  13. Chawla D, Rees G, Friston KJ (1999) The physiological basis of attentional modulation in extrastriate visual areas. Nat Neurosci 2:671–676CrossRefPubMedGoogle Scholar
  14. Collette F, Van der Linden M (2002) Brain imaging of the central executive component of working memory. Neurosci Biobehav Rev 26:105–125CrossRefPubMedGoogle Scholar
  15. Corbetta M, Shulman GL (2002) Control of goal-directed and stimulus-driven attention in the brain. Nat Rev Neurosci 3:201–215CrossRefPubMedGoogle Scholar
  16. Cox RW (1996) AFNI: software for analysis and visualization of functional magnetic resonance neuroimages. Comput Biomed Res 29:162–173CrossRefPubMedGoogle Scholar
  17. Craig AD (2009) How do you feel—now? The anterior insula and human awareness. Nat Rev Neurosci 10:59–70CrossRefPubMedGoogle Scholar
  18. De Pisapia N, Braver TS (2008) Preparation for integration: the role of anterior prefrontal cortex in working memory. NeuroReport 19:15–19CrossRefPubMedGoogle Scholar
  19. De Pisapia N, Slomski JA, Braver TS (2007) Functional specializations in lateral prefrontal cortex associated with the integration and segregation of information in working memory. Cereb Cortex 17:993–1006CrossRefPubMedGoogle Scholar
  20. Dosenbach NUF, Visscher KM, Palmer ED, Miezin FM, Wenger KK, Kang HSC, Burgund ED, Grimes AL, Schlaggar BL, Petersen SE (2006) A core system for the implementation of task sets. Neuron 50:799–812CrossRefPubMedGoogle Scholar
  21. Dosenbach NUF, Fair DA, Miezin FM, Cohen AL, Wenger KK, Dosenbach RAT, Fox MD, Snyder AZ, Vincent JL, Raichle ME, Schlaggar BL, Petersen SE (2007) Distinct brain networks for adaptive and stable task control in humans. Proc Natl Acad Sci U S A 104:11073–11078CrossRefPubMedGoogle Scholar
  22. Dosenbach NUF, Fair DA, Cohen AL, Schlaggar BL, Petersen SE (2008) A dual-networks architecture of top-down control. Trends Cogn Sci 12:99–105CrossRefPubMedGoogle Scholar
  23. Ernst M, Heishman SJ, Spurgeon L, London ED (2001a) Smoking history and nicotine effects on cognitive performance. Neuropsychopharmacology 25:313–319CrossRefPubMedGoogle Scholar
  24. Ernst M, Matochik JA, Heishman SJ, Van Horn JD, Jons PH, Henningfield JE, London ED (2001b) Effect of nicotine on brain activation during performance of a working memory task. Proc Natl Acad Sci U S A 98:4728–4733CrossRefPubMedGoogle Scholar
  25. Evans DE, Drobes DJ (2009) Nicotine self-medication of cognitive-attentional processing. Addict Biol 14:32–42CrossRefPubMedGoogle Scholar
  26. Fan J, McCandliss BD, Sommer T, Raz A, Posner MI (2002) Testing the efficiency and independence of attentional networks. J Cogn Neurosci 14:340–347CrossRefPubMedGoogle Scholar
  27. Fan J, McCandliss BD, Fossella J, Flombaum JI, Posner MI (2005) The activation of attentional networks. Neuroimage 26:471–479CrossRefPubMedGoogle Scholar
  28. Fox MD, Snyder AZ, Vincent JL, Corbetta M, Van Essen DC, Raichle ME (2005) The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc Natl Acad Sci U S A 102:9673–9678CrossRefPubMedGoogle Scholar
  29. Garavan H (1998) Serial attention within working memory. Mem Cogn 26:263–276Google Scholar
  30. Garavan H, Ross TJ, Li SJ, Stein EA (2000) A parametric manipulation of central executive functioning. Cereb Cortex 10:585–592CrossRefPubMedGoogle Scholar
  31. Gehring WJ, Bryck RL, Jonides J, Albin RL, Badre D (2003) The mind’s eye, looking inward? In search of executive control in internal attention shifting. Psychophysiology 40:572–585CrossRefPubMedGoogle Scholar
  32. Greenstein JE, Kassel JD (2009) The effects of smoking and smoking abstinence on verbal and visuospatial working memory capacity. Exp Clin Psychopharmacol 17:78–90CrossRefPubMedGoogle Scholar
  33. Gusnard DA, Akbudak E, Shulman GL, Raichle ME (2001) Medial prefrontal cortex and self-referential mental activity: relation to a default mode of brain function. Proc Natl Acad Sci U S A 98:4259–4264CrossRefPubMedGoogle Scholar
  34. Hahn B, Ross TJ, Yang Y, Kim I, Huestis MA, Stein EA (2007) Nicotine enhances visuospatial attention by deactivating areas of the resting brain default network. J Neurosci 27:3477–3489CrossRefPubMedGoogle Scholar
  35. Heatherton TF, Kozlowski LT, Frecker RC, Fagerstrom KO (1991) The Fagerstrom Test for Nicotine Dependence: a revision of the Fagerstrom Tolerance Questionnaire. Br J Addict 86:1119–1127CrossRefPubMedGoogle Scholar
  36. Heishman SJ, Singleton EG, Moolchan ET (2003) Tobacco craving questionnaire: reliability and validity of a new multifactorial instrument. Nicotine Tob Res 5:645–654CrossRefPubMedGoogle Scholar
  37. Heishman SJ, Kleykamp BA, Singleton EG (2010) Meta-analysis of the acute effects of nicotine and smoking on human performance. Psychopharmacology 210:453–469CrossRefPubMedGoogle Scholar
  38. Hester R, Garavan H (2009) Neural mechanisms underlying drug-related cue distraction in active cocaine users. Pharmacol Biochem Behav 93:270–277CrossRefPubMedGoogle Scholar
  39. Jacobsen LK, D’Souza DC, Mencl WE, Pugh KR, Skudlarski P, Krystal JH (2004) Nicotine effects on brain function and functional connectivity in schizophrenia. Biol Psychiatry 55:850–858CrossRefPubMedGoogle Scholar
  40. Jacobsen LK, Krystal JH, Mencl WE, Westerveld M, Frost SJ, Pugh KR (2005) Effects of smoking and smoking abstinence on cognition in adolescent tobacco smokers. Biol Psychiatry 57:56–66CrossRefPubMedGoogle Scholar
  41. Jacobsen LK, Pugh KR, Mencl WE, Gelernter J (2006) C957T polymorphism of the dopamine D2 receptor gene modulates the effect of nicotine on working memory performance and cortical processing efficiency. Psychopharmacology 188:530–540CrossRefPubMedGoogle Scholar
  42. Jacobsen LK, Mencl WE, Constable RT, Westerveld M, Pugh KR (2007) Impact of smoking abstinence on working memory neurocircuitry in adolescent daily tobacco smokers. Psychopharmacology 193:557–566CrossRefPubMedGoogle Scholar
  43. Kleykamp BA, Jennings JM, Blank MD, Eissenberg T (2005) The effects of nicotine on attention and working memory in never-smokers. Psychol Addict Behav 19:433–438CrossRefPubMedGoogle Scholar
  44. Koechlin E, Basso G, Pietrini P, Panzer S, Grafman J (1999) The role of the anterior prefrontal cortex in human cognition. Nature 399:148–151CrossRefPubMedGoogle Scholar
  45. Kübler A, Murphy K, Kaufman J, Stein EA, Garavan H (2003) Co-ordination within and between verbal and visuospatial working memory: network modulation and anterior frontal recruitment. Neuroimage 20:1298–1308CrossRefPubMedGoogle Scholar
  46. Kübler A, Murphy K, Garavan H (2005) Cocaine dependence and attention switching within and between verbal and visuospatial working memory. Eur J Neurosci 21:1984–1992CrossRefPubMedGoogle Scholar
  47. Kumari V, Gray JA, Ffytche DH, Mitterschiffthaler MT, Das M, Zachariah E, Vythelingum GN, Williams SCR, Simmons A, Sharma T (2003) Cognitive effects of nicotine in humans: an fMRI study. Neuroimage 19:1002–1013CrossRefPubMedGoogle Scholar
  48. Lawrence NS, Ross TJ, Stein EA (2002) Cognitive mechanisms of nicotine on visual attention. Neuron 36:539–548CrossRefPubMedGoogle Scholar
  49. Levin ED, McClernon FJ, Rezvani AH (2006) Nicotinic effects on cognitive function: behavioral characterization, pharmacological specification, and anatomic localization. Psychopharmacology 184:523–539CrossRefPubMedGoogle Scholar
  50. Li ZH, Sun XW, Wang ZX, Zhang XC, Zhang DR, He S, Hu XP (2004) Behavioral and functional MRI study of attention shift in human verbal working memory. Neuroimage 21:181–191CrossRefPubMedGoogle Scholar
  51. 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 14:820–826CrossRefPubMedGoogle Scholar
  52. Loughead J, Ray R, Wileyto EP, Ruparel K, Sanborn P, Siegel S, Gur RC, Lerman C (2010) Effects of the alpha 4 beta 2 partial agonist varenicline on brain activity and working memory in abstinent smokers. Biol Psychiatry 67:715–721CrossRefPubMedGoogle Scholar
  53. Mansvelder HD, van Aerde KI, Couey JJ, Brussaard AB (2006) Nicotinic modulation of neuronal networks: from receptors to cognition. Psychopharmacology 184:292–305CrossRefPubMedGoogle Scholar
  54. Marchant NL, Trawley S, Rusted JM (2008) Prospective memory or prospective attention: physiological and pharmacological support for an attentional model. Int J Neuropsychopharmacol 11:401–411CrossRefPubMedGoogle Scholar
  55. Marchant NL, Kamel F, Echlin K, Grice J, Lewis M, Rusted JM (2009) Modafinil improves rapid shifts of attention. Psychopharmacology 202:487–495CrossRefPubMedGoogle Scholar
  56. McClernon FJ, Hiott FB, Huettel SA, Rose JE (2005) Abstinence-induced changes in self-report craving correlate with event-related fMRI responses to smoking cues. Neuropsychopharmacology 30:1940–1947CrossRefPubMedGoogle Scholar
  57. McClernon FJ, Kozink RV, Lutz AM, Rose JE (2009) 24-h smoking abstinence potentiates fMRI-BOLD activation to smoking cues in cerebral cortex and dorsal striatum. Psychopharmacology 204:25–35CrossRefPubMedGoogle Scholar
  58. Mendrek A, Monterosso J, Simon SL, Jarvik M, Brody A, Olmstead R, Domier CP, Cohen MS, Ernst M, London ED (2006) Working memory in cigarette smokers: comparison to non-smokers and effects of abstinence. Addict Behav 31:833–844CrossRefPubMedGoogle Scholar
  59. Myers CS, Taylor RC, Moolchan ET, Heishman SJ (2008) Dose-related enhancement of mood and cognition in smokers administered nicotine nasal spray. Neuropsychopharmacology 33:588–598CrossRefPubMedGoogle Scholar
  60. Naghavi HR, Nyberg L (2005) Common fronto-parietal activity in attention, memory, and consciousness: shared demands on integration? Conscious Cogn 14:390–425CrossRefPubMedGoogle Scholar
  61. Naqvi NH, Rudrauf D, Damasio H, Bechara A (2007) Damage to the insula disrupts addiction to cigarette smoking. Science 315:531–534CrossRefPubMedGoogle Scholar
  62. Newhouse PA, Potter A, Singh A (2004) Effects of nicotinic stimulation on cognitive performance. Curr Opin Pharmacol 4:36–46CrossRefPubMedGoogle Scholar
  63. Owen AM, McMillan KM, Laird AR, Bullmore E (2005) N-back working memory paradigm: a meta-analysis of normative functional neuroimaging. Hum Brain Mapp 25:46–59CrossRefPubMedGoogle Scholar
  64. Parrott AC, Garnham NJ, Wesnes K, Pincock C (1996) Cigarette smoking and abstinence: comparative effects upon cognitive task performance and mood state over 24 h. Hum Psychopharmacol 11:391–400CrossRefGoogle Scholar
  65. Patterson F, Jepson C, Strasser AA, Loughead J, Perkins KA, Gur RC, Frey JM, Siegel S, Lerman C (2009) Varenicline improves mood and cognition during smoking abstinence. Biol Psychiatry 65:144–149CrossRefPubMedGoogle Scholar
  66. Patterson F, Jepson C, Loughead J, Perkins K, Strasser AA, Siegel S, Frey J, Gur R, Lerman C (2010) Working memory deficits predict short-term smoking resumption following brief abstinence. Drug Alcohol Depend 106:61–64CrossRefPubMedGoogle Scholar
  67. Paulus MP, Tapert SF, Schuckit MA (2005) Neural activation patterns of methamphetamine-dependent subjects during descision making predict relapse. Arch Gen Psychiatry 62:761–768CrossRefPubMedGoogle Scholar
  68. Posner MI, Petersen SE (1990) The attention system of the human brain. Annu Rev Neurosci 13:25–42CrossRefPubMedGoogle Scholar
  69. Posner MI, Rothbart MK (2007) Research on attention networks as a model for the integration of psychological science. Annu Rev Psychol 58:1–23CrossRefPubMedGoogle Scholar
  70. R-Development-Core-Team (2009) R: a language and environment for statistical computing. R Foundation for Statistical Computing; Vienna, Austria; ISBN: 3-900051-07-0; http://www.R-project.org
  71. Reynolds JR, West R, Braver T (2009) Distinct neural circuits support transient and sustained processes in prospective memory and working memory. Cereb Cortex 19:1208–1221CrossRefPubMedGoogle Scholar
  72. Rezvani AH, Levin ED (2001) Cognitive effects of nicotine. Biol Psychiatry 49:258–267CrossRefPubMedGoogle Scholar
  73. Rusted JM, Trawley S, Heath J, Kettle G, Walker H (2005) Nicotine improves memory for delayed intentions. Psychopharmacology 182:355–365CrossRefPubMedGoogle Scholar
  74. Rusted J, Sawyer R, Jones C, Trawley S, Marchant N (2009) Positive effects of nicotine on cognition: the deployment of attention for prospective memory. Psychopharmacology 202:93–102CrossRefPubMedGoogle Scholar
  75. Sakai K (2008) Task set and prefrontal cortex. Annu Rev Neurosci 31:219–245CrossRefPubMedGoogle Scholar
  76. Shakleya DM, Huestis MA (2009) Simultaneous and sensitive measurement of nicotine, cotinine, trans-3′-hydroxycotinine and norcotinine in human plasma by liquid chromatography–tandem mass spectrometry. J Chromatogr B Anal Technol Biomed Life Sci 877:3537–3542CrossRefGoogle Scholar
  77. Simons JS, Scholvinck ML, Gilbert SJ, Frith CD, Burgess PW (2006) Differential components of prospective memory? Evidence from fMRI. Neuropsychologia 44:1388–1397CrossRefPubMedGoogle Scholar
  78. Smith EE, Jonides J, Koeppe RA (1996) Dissociating verbal and spatial working memory using PET. Cereb Cortex 6:11–20CrossRefPubMedGoogle Scholar
  79. Sylvester CYC, Wager TD, Lacey SC, Hernandez L, Nichols TE, Smith EE, Jonides J (2003) Switching attention and resolving interference: fMRI measures of executive functions. Neuropsychologia 41:357–370CrossRefPubMedGoogle Scholar
  80. Talairach J, Tourneaux P (1988) Co-planar stereotaxic atlas of the human brain. Thieme Medical, New YorkGoogle Scholar
  81. Thienel R, Kellermann T, Schall U, Voss B, Reske M, Halfter S, Sheldrick AJ, Radenbach K, Habel U, Shah NJ, Kircher T (2009a) Muscarinic antagonist effects on executive control of attention. Int J Neuropsychopharmacol 12:1307–1317CrossRefPubMedGoogle Scholar
  82. Thienel R, Voss B, Kellermann T, Reske M, Halfter S, Sheldrick AJ, Radenbach K, Habel U, Shah NJ, Schall U, Kircher T (2009b) Nicotinic antagonist effects on functional attention networks. Int J Neuropsychopharmacol 12:1295–1305CrossRefPubMedGoogle Scholar
  83. Visscher KM, Miezin FM, Kelly JE, Buckner RL, Donaldson DI, McAvoy MP, Bhalodia VM, Petersen SE (2003) Mixed blocked/event-related designs separate transient and sustained activity in fMRI. Neuroimage 19:1694–1708CrossRefPubMedGoogle Scholar
  84. Warburton DM, Rusted JM (1993) Cholinergic control of cognitive resources. Neuropsychobiology 28:43–46CrossRefPubMedGoogle Scholar
  85. Wechsler D (1999) Wechsler abbreviated scale of intelligence, 3rd edn. The Psychological Corporation, San AntonioGoogle Scholar
  86. Xu JS, Mendrek A, Cohen MS, Monterosso J, Rodriguez P, Simon SL, Brody A, Jarvik M, Domier CP, Olmstead R, Ernst M, London ED (2005) Brain activity in cigarette smokers performing a working memory task: effect of smoking abstinence. Biol Psychiatry 58:143–150CrossRefPubMedGoogle Scholar
  87. Xu JS, Mendrek A, Cohen MS, Monterosso J, Simon S, Brody AL, Jarvik M, Rodriguez P, Ernst M, London ED (2006) Effects of acute smoking on brain activity vary with abstinence in smokers performing the N-Back Task: a preliminary study. Psychiatry Res 148:103–109CrossRefPubMedGoogle Scholar

Copyright information

© US Government 2010

Authors and Affiliations

  • Matthew T. Sutherland
    • 1
    Email author
  • Thomas J. Ross
    • 1
  • Diaá M. Shakleya
    • 2
  • Marilyn A. Huestis
    • 2
  • Elliot A. Stein
    • 1
  1. 1.Neuroimaging Research BranchNational Institute on Drug Abuse-Intramural Research Program, NIH/DHHSBaltimoreUSA
  2. 2.Chemistry and Drug Metabolism SectionNational Institute on Drug Abuse-Intramural Research Program, NIH/DHHSBaltimoreUSA

Personalised recommendations