Skip to main content

Advertisement

SpringerLink
Log in

Nicotine increases anterior insula activation to expected and unexpected outcomes among nonsmokers

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

Tobacco has a higher rate of dependence than other drugs of abuse. However, the psychopharmacological effects of nicotine are incongruent with the tenacity of tobacco addiction since nicotine does not produce robust euphoria in humans or self-administration in rodents. A potential explanation is that nicotine amplifies the salience of other stimuli that have some incentive value, which could influence the initiation and persistence of smoking. However, the neural mechanisms of this process are unknown.

Objectives

One way that nicotine may amplify the salience of other stimuli is by enhancing reward prediction errors. We hypothesized that nicotine would enhance the neural response to unexpected (relative to expected) rewards compared to placebo.

Methods

Twenty-three nonsmokers underwent two fMRI scans, following nicotine (1 mg) or placebo administration, while performing an outcome expectation task. In the task, a pair of cues was associated with either a subsequent reward (the image of a $100 bill) or a nonreward (the image of a blurry rectangle). On 20% of trials, the cue was followed by an unexpected outcome.

Results

Although nicotine did not affect the magnitude of prediction errors relative to placebo, nicotine did increase BOLD activation in the anterior insula/inferior frontal gyrus and decrease activation in the caudate across all outcome types (including both rewards and nonrewards).

Conclusions

The insula and caudate could play a role in the initial effects of nicotine in nonsmokers, and these changes in baseline may be the mechanism that underlies how nicotine amplifies the salience of nondrug stimuli.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Abler B, Walter H, Erk S, Kammerer H, Spitzer M (2006) Prediction error as a linear function of reward probability is coded in human nucleus accumbens. NeuroImage 31:790–795

    Article  PubMed  Google Scholar 

  • Anthony JC, Warner LA, Kessler RC (1994) Comparative epidemiology of dependence on tobacco, alchohol, controlled substances, and inhalants: basic findings from the national comorbidity survey. Exp Clin Psychopharm 2:244–268

    Article  Google Scholar 

  • Aron AR, Robbins TW, Poldrack RA (2014) Inhibition and the right inferior frontal cortex: one decade on. Trends Cogn Sci 18:177–185

    Article  PubMed  Google Scholar 

  • Baker TB, Piper ME, McCarthy DE, Majeskie MR, Fiore MC (2004) Addiction motivation reformulated: an affective processing model of negative reinforcement. Psychol Rev 111:33–51

    Article  PubMed  Google Scholar 

  • Barr RS, Pizzagalli DA, Culhane MA, Goff DC, Evins AE (2008) A single dose of nicotine enhances reward responsiveness in nonsmokers: implications for development of dependence. Biol Psychiat 63:1061–1065

    Article  CAS  PubMed  Google Scholar 

  • Bevins RA, Palmatier MI (2004) Extending the role of associative learning processes in nicotine addiction. Behav Cogn Neurosci Rev 3:143–158

    Article  PubMed  Google Scholar 

  • Brody AL, Mandelkern MA, London ED, Olmstead RE, Farahi J, Scheibal D, Jou J, Allen V, Tiongson E, Chefer SI, Koren AO, Mukhin AG (2006) Cigarette smoking saturates brain alpha(4)beta(2) nicotinic acetylcholine receptors. Arch Gen Psychiat 63:907–915

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Caggiula AR, Donny EC, White AR, Chaudhri N, Booth S, Gharib MA, Hoffman A, Perkins KA, Sved AF (2001) Cue dependency of nicotine self-administration and smoking. Pharmacol Biochem Be 70:515–530

    Article  CAS  Google Scholar 

  • Caggiula AR, Donny EC, Palmatier MI, Liu X, Chaudhri N, Sved AF (2009) The role of nicotine in smoking: a dual-reinforcement model. Neb Symp Motiv 55:91–109

    Article  Google Scholar 

  • Cai WD, Ryali S, Chen TW, Li CSR, Menon V (2014) Dissociable roles of right inferior frontal cortex and anterior insula in inhibitory control: evidence from intrinsic and task-related functional parcellation, connectivity, and response profile analyses across multiple datasets. J Neurosci 34:14652–14667

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Caspers S, Schleicher A, Bacha-Trams M, Palomero-Gallagher N, Amunts K, Zilles K (2013) Organization of the human inferior parietal lobule based on receptor architectonics. Cereb Cortex 23:615–628

    Article  PubMed  Google Scholar 

  • CDC (2011) Tobacco use: targeting the nation’s leading killer at a glance. Center for Disease Control and Prevention, Atlanta

    Google Scholar 

  • Chang LJ, Yarkoni T, Khaw MW, Sanfey AG (2013) Decoding the role of the insula in human cognition: functional parcellation and large-scale reverse inference. Cereb Cortex 23:739–749

    Article  PubMed  Google Scholar 

  • Chowdhury R, Guitart-Masip M, Lambert C, Dayan P, Huys Q, Duzel E, Dolan RJ (2013) Dopamine restores reward prediction errors in old age. Nat Neurosci 16:648–653

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Craig AD (2009) How do you feel - now? The anterior insula and human awareness. Nat Rev Neurosci 10:59–70

    Article  CAS  PubMed  Google Scholar 

  • Dar R, Kaplan R, Shaham L, Frenk H (2007) Euphoriant effects of nicotine in smokers: fact or artifact? Psychopharmacology 191:203–210

    Article  CAS  PubMed  Google Scholar 

  • Dawkins L, Powell JH, West R, Powell J, Pickering A (2006) A double-blind placebo controlled experimental study of nicotine: I - effects on incentive motivation. Psychopharmacology 189:355–367

    Article  CAS  PubMed  Google Scholar 

  • Di Chiara G (2000) Role of dopamine in the behavioural actions of nicotine related to addiction. Eur J Pharmacol 393:295–314

    Article  CAS  PubMed  Google Scholar 

  • Di Chiara G, Imperato A (1988) Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc Natl Acad Sci U S A 85:5274–5278

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Donny EC, Houtsmuller E, Stitzer ML (2007) Smoking in the absence of nicotine: behavioral, subjective and physiological effects over 11 days. Addiction 102:324–334

    Article  PubMed  Google Scholar 

  • Ettinger U, Williams SCR, Patel D et al (2009) Effects of acute nicotine on brain function in healthy smokers and non-smokers: estimation of inter-individual response heterogeneity. Neuroimage 45:549–561

  • Fedota JR, Sutherland MT, Salmeron BJ, Ross TJ, Hong LE, Stein EA (2015) Reward anticipation is differentially modulated by varenicline and nicotine in smokers. Neuropsychopharmacol 40:2038–2046

    Article  CAS  Google Scholar 

  • Froeliger, B., McConnell, P.A., Bell, S., Sweitzer, M., Kozink, R.V., Eichberg, C., Hallyburton, M., Kaiser, N., Gray, K. M., McClernon, F. J. (2017). A corticothalamic pathway mediates inhibitory control and smoking relapse vulnerability. JAMA Psychiat (in press)

  • Garavan H (2010) Insula and drug cravings. Brain Struct Funct 214:593–601

    Article  PubMed  Google Scholar 

  • Garrison J, Erdeniz B, Done J (2013) Prediction error in reinforcement learning: a meta-analysis of neuroimaging studies. Neurosci Biobehav Rev 37:1297–1310

    Article  PubMed  Google Scholar 

  • Gourlay SG, Benowitz NL (1997) Arteriovenus differences in plasma concentration of nicotine and catecholamines and related cardiovascular effects after smoking, nicotine nasal spray, and intravenous nicotine. Clin Pharmacol Ther 62:453–463

    Article  CAS  PubMed  Google Scholar 

  • Gu X, Lohrenz T, Salas R, Baldwin PR, Soltani A, Kirk U, Cinciripini PM, Montague PR (2015) Belief about nicotine selectively modulates value and reward prediction error signals in smokers. PNAS 112:2539–2544

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 27:3477–3489

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hampshire A, Chamberlain SR, Monti MM, Duncan J, Owen AM (2010) The role of the right inferior frontal gyrus: inhibition and attentional control. NeuroImage 50:1313–1319

    Article  PubMed  PubMed Central  Google Scholar 

  • Hanlon CA, Dowdle LT, Naselaris T, Canterberry M, Cortese BM (2014) Visual cortex activation to drug cues: a meta-analysis of functional neuroimaging papers in addiction and substance abuse literature. Drug Alcohol Depen 143:206–212

    Article  Google Scholar 

  • Heishman SJ, Kleykamp BA, Singleton EG (2010) Meta-analysis of the acute effects of nicotine and smoking on human performance. Psychopharmacology 210:453–469

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kandel D, Chen K, Warner LA, Kessler RC, Grant B (1997) Prevalence and demographic correlates of symptoms of last year dependence on alcohol, nicotine, marijuana and cocaine in the US population. Drug Alcohol Depen 44:11–29

    Article  CAS  Google Scholar 

  • 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 19:1002–1013

    Article  PubMed  Google Scholar 

  • Levin ED, McClernon FJ, Rezvani AH (2006) Nicotinic effects on cognitive function: behavioral characterization, pharmacological specification, and anatomic localization. Psychopharmacology 184:523–539

    Article  CAS  PubMed  Google Scholar 

  • Lopez-Quintero C, de los Cobos JP, Hasin DS, Okuda M, Wang S, Grant BF, Blanco C (2011) Probability and predictors of transition from first use to dependence on nicotine, alcohol, cannabis, and cocaine: results of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Drug Alcohol Depen 115:120–130

    Article  Google Scholar 

  • Marchant NL, King SL, Tabet N, Rusted JM (2010) Positive effects of cholinergic stimulation favor young APOE epsilon 4 carriers. Neuropsychopharmacol 35:1090–1096

    Article  CAS  Google Scholar 

  • McClernon FJ, Conklin CA, Kozink RV et al (2016) Hippocampal and insular response to smoking-related environments: neuroimaging evidence for drug-context effects in nicotine dependence. Neuropsychopharmacology 41:877–885

  • McClure SM, Berns GS, Montague PR (2003) Temporal prediction errors in a passive learning task activate human striatum. Neuron 38:339–346

    Article  CAS  PubMed  Google Scholar 

  • Menon V, Uddin LQ (2010) Saliency, switching, attention and control: a network model of insula function. Brain Struct Funct 214:655–667

    Article  PubMed  PubMed Central  Google Scholar 

  • Morris RW, Vercammen A, Lenroot R, Moore L, Langton J, Short B, Kulkarni J, Curtis J, O'Donnell M, Weickert CS, Weickert TW (2012) Disambiguating ventral striatum fMRI-related bold signal during reward prediction in schizophrenia. Mol Psychiatr 17:280–289

    Article  Google Scholar 

  • Murray GK, Corlett PR, Clark L, Pessiglione M, Blackwell AD, Honey G, Jones PB, Bullmore ET, Robbins TW, Fletcher PC (2008) Substantia nigra/ventral tegmental reward prediction error disruption in psychosis. Mol Psychiatr 13:267–276

    Article  CAS  Google Scholar 

  • Naqvi NH, Bechara A (2009) The hidden island of addiction: the insula. Trends Neurosci 32:56–67

    Article  CAS  PubMed  Google Scholar 

  • Newhouse PA, Potter AS, Dumas JA, Thiel CM (2011) Functional brain imaging of nicotinic effects on higher cognitive processes. Biochem Pharmacol 82:943–951

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nguyen QB, Zhu SH (2009) Intermittent smokers who used to smoke daily: a preliminary study on smoking situations. Nicotine Tob Res 11:164–170

    Article  PubMed  PubMed Central  Google Scholar 

  • Niendam TA, Laird AR, Ray KL, Dean YM, Glahn DC, Carter CS (2012) Meta-analytic evidence for a superordinate cognitive control network subserving diverse executive functions. Cogn Affect Behav Ne 12:241–268

    Article  Google Scholar 

  • O'Doherty JP, Dayan P, Friston K, Critchley H, Dolan RJ (2003) Temporal difference models and reward-related learning in the human brain. Neuron 38:329–337

    Article  PubMed  Google Scholar 

  • Perkins KA, Grottenthaler A, Wilson AS (2009) Lack of reinforcement enhancing effects of nicotine in non-dependent smokers. Psychopharmacology 205:635–645

    Article  CAS  PubMed  Google Scholar 

  • Pessiglione M, Seymour B, Flandin G, Dolan RJ, Frith CD (2006) Dopamine-dependent prediction errors underpin reward-seeking behaviour in humans. Nature 442:1042–1045

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ramnani N, Elliott R, Athwal BS, Passinghm RE (2004) Prediction error for free monetary reward in the human prefrontal cortex. NeuroImage 23:777–786

    Article  CAS  PubMed  Google Scholar 

  • Redish AD (2004) Addiction as a computational process gone awry. Science 306:1944–1947

    Article  CAS  PubMed  Google Scholar 

  • Rezvani AH, Levin ED (2001) Cognitive effects of nicotine. Biol Psychiat 49:258–267

    Article  CAS  PubMed  Google Scholar 

  • Rice ME, Cragg SJ (2004) Nicotine amplifies reward-related dopamine signals in striatum. Nat Neurosci 7:583–584

    Article  CAS  PubMed  Google Scholar 

  • Rose JE, Corrigall WA (1997) Nicotine self-administration in animals and humans: similarities and differences. Psychopharmacology 130:28–40

    Article  CAS  PubMed  Google Scholar 

  • Rose EJ, Ross TJ, Salmeron BJ, Lee M, Shakleya DM, Huestis M, Stein EA (2012) Chronic exposure to nicotine is associated with reduced reward-related activity in the striatum but not the midbrain. Biol Psychiat 71:206–213

    Article  CAS  PubMed  Google Scholar 

  • Rose EJ, Ross TJ, Salmeron BJ, Lee M, Shakleya DM, Huestis M, Stein EA (2013) Acute nicotine differentially impacts anticipatory valence- and magnitude-related striatal activity. Biol Psychiatry 73:280–288

    Article  CAS  PubMed  Google Scholar 

  • 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 202:93–102

    Article  CAS  PubMed  Google Scholar 

  • Rusted J, Ruest T, Gray MA (2011) Acute effects of nicotine administration during prospective memory, an event related fMRI study. Neuropsychologia 49:2362–2368

    Article  PubMed  Google Scholar 

  • Schultz W (2011) Potential vulnerabilities of neuronal reward, risk, and decision mechanisms to addictive drugs. Neuron 69:603–617

    Article  CAS  PubMed  Google Scholar 

  • Schultz W, Dickinson A (2000) Neuronal coding of prediction errors. Annu Rev Neurosci 23:473–500

    Article  CAS  PubMed  Google Scholar 

  • Schultz W, Dayan P, Montague PR (1997) A neural substrate of prediction and reward. Science 275:1593–1599

    Article  CAS  PubMed  Google Scholar 

  • Smith JL, Mattick RP, Jamadar SD, Iredale JM (2014) Deficits in behavioural inhibition in substance abuse and addiction: a meta-analysis. Drug Alcohol Depend 145:1–33

    Article  PubMed  Google Scholar 

  • Sutherland MT, Ray KL, Riedel MC, Yanes JA, Stein EA, Laird AR (2015) Neurobiological impact of nicotinic acetylcholine receptor agonists: an activation likelihood estimation meta-analysis of pharmacologic neuroimaging studies. Biol Psychiatry 78:711–720

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Watkins SS, Koob GF, Markou A (2000) Neural mechanisms underlying nicotine addiction: acute positive reinforcement and withdrawal. Nicotine Tob Res 2:19–37

    Article  CAS  PubMed  Google Scholar 

  • Watson D, Clark LA, Tellegen A (1988) Development and validation of brief measures of positive and negative affect—the Panas scales. J Pers Soc Psychol 54:1063–1070

    Article  CAS  PubMed  Google Scholar 

  • Wignall ND, de Wit H (2011) Effects of nicotine on attention and inhibitory control in healthy nonsmokers. Exp Clin Psychopharm 19:183–191

    Article  CAS  Google Scholar 

  • Worsley KJ (2001) Statistical analysis of activation images. Ch 14. In: Jezzard P, Matthews PM, Smith SM (eds) Functional MRI: an introduction to methods. University Press, Oxford

    Google Scholar 

  • Zhang H, Sulzer D (2004) Frequency-dependent modulation of dopamine release by nicotine. Nat Neurosci 7:581–582

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by NIDA K01 DA033347 (MAA).

Author information

Authors and Affiliations

  1. Department of Psychiatry and Behavioral Science, Duke University School of Medicine, Durham, NC, 27710, USA

    Merideth A. Addicott, Jason A. Oliver & F. Joseph McClernon

  2. Duke-University of North Carolina Brain Imaging and Analysis Center (BIAC), Duke University School of Medicine, Durham, NC, 27710, USA

    Merideth A. Addicott, Jason A. Oliver & F. Joseph McClernon

Authors
  1. Merideth A. Addicott
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jason A. Oliver
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F. Joseph McClernon
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Merideth A. Addicott.

Ethics declarations

Participants provided informed consent, and this protocol was approved by the Duke University’s Institutional Review Board.

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Addicott, M.A., Oliver, J.A. & Joseph McClernon, F. Nicotine increases anterior insula activation to expected and unexpected outcomes among nonsmokers. Psychopharmacology 234, 1145–1154 (2017). https://doi.org/10.1007/s00213-017-4550-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-017-4550-8

Keywords

Search

Navigation