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The insula and drug addiction: an interoceptive view of pleasure, urges, and decision-making

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Abstract

We have recently shown that damage to the insula leads to a profound disruption of addiction to cigarette smoking (Naqvi et al., Science 315:531–534, 2007). Yet, there is little understanding of why the insula should play such an important role in an addictive behavior. A broad literature (much of it reviewed in this issue) has addressed the role of the insula in processes related to conscious interoception, emotional experience, and decision-making. Here, we review evidence for the role of the insula in drug addiction, and propose a novel theoretical framework for addiction in which the insula represents the interoceptive effects of drug taking, making this information available to conscious awareness, memory and executive functions. A central theme of this framework is that a primary goal for the addicted individual is to obtain the effects of the drug use ritual upon the body, and representations of this goal in interoceptive terms by the insula contribute to how addicted individuals feel, remember, and decide about taking drugs. This makes drug addiction like naturally motivated behaviors, such as eating and sex, for which an embodied ritual is the primary goal.

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References

  • Allen GV et al (1991) Organization of visceral and limbic connections in the insular cortex of the rat. J Comp Neurol 311:1–16

    Article  PubMed  CAS  Google Scholar 

  • Allman JM, Tetreault NA, Hakeem AY, Manaye KF, Semendeferi K, Erwin JM, Goubert V, Hof PR (2010) The von Economo neurons in frontoinsular and anterior cingulate cortex in great apes and humans. Brain Struc Func 214(5-6). doi:10.1007/s00429-010-0254-0 (this issue)

  • Arnow BA et al (2002) Brain activation and sexual arousal in healthy, heterosexual males. Brain 125:1014–1023

    Article  PubMed  Google Scholar 

  • Balleine BW, Dickinson A (2000) The effect of lesions of the insular cortex on instrumental conditioning: evidence for a role in incentive memory. J Neurosci 20:8954–8964

    PubMed  CAS  Google Scholar 

  • Bechara A (2005) Decision making, impulse control and loss of willpower to resist drugs: a neurocognitive perspective. Nat Neurosci 8:1458–1463

    Article  PubMed  CAS  Google Scholar 

  • Bechara A, Damasio H (2002) Decision-making and addiction (part I): impaired activation of somatic states in substance dependent individuals when pondering decisions with negative future consequences. Neuropsychologia 40:1675–1689

    Article  PubMed  Google Scholar 

  • Bechara A, Naqvi N (2004) Listening to your heart: interoceptive awareness as a gateway to feeling. Nat Neurosci 7:102–103

    Article  PubMed  CAS  Google Scholar 

  • Bechara A, van der Kooy D (1985) Opposite motivational effects of endogenous opioids in brain and periphery. Nature 314:533–534

    Article  PubMed  CAS  Google Scholar 

  • Bechara A et al (1997) Deciding advantageously before knowing the advantageous strategy. Science 275:1293–1295

    Article  PubMed  CAS  Google Scholar 

  • Berke JD, Hyman SE (2000) Addiction, dopamine, and the molecular mechanisms of memory. Neuron 25:515–532

    Article  PubMed  CAS  Google Scholar 

  • Berridge KC, Robinson TE (1998) What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience? Brain Res Brain Res Rev 28:309–369

    Article  PubMed  CAS  Google Scholar 

  • Berridge KC, Robinson TE (2003) Parsing reward. Trends Neurosci 26:507–513

    Article  PubMed  CAS  Google Scholar 

  • Berthier M et al (1988) Asymbolia for pain: a sensory-limbic disconnection syndrome. Ann Neurol 24:41–49

    Article  PubMed  CAS  Google Scholar 

  • Bonson KR et al (2002) Neural systems and cue-induced cocaine craving. Neuropsychopharmacology 26:376–386

    Google Scholar 

  • Bossaerts P (2010) Risk and risk prediction error signals in anterior insula. Brain Struc Func 214(5-6). doi:10.1007/s00429-010-0253-1 (this issue)

  • Brody AL et al (2002) Brain metabolic changes during cigarette craving. Arch Gen Psychiatry 59:1162–1172

    Article  PubMed  Google Scholar 

  • Brody AL et al (2007) Neural substrates of resisting craving during cigarette cue exposure. Biol Psychiatry 62:642–651

    Article  PubMed  CAS  Google Scholar 

  • Calder AJ et al (2000) Impaired recognition and experience of disgust following brain injury. Nat Neurosci 3:1077–1078

    Article  PubMed  CAS  Google Scholar 

  • Chikama M et al (1997) Insular cortical projections to functional regions of the striatum correlate with cortical cytoarchitectonic organization in the primate. J Neurosci 17:9686–9705

    PubMed  CAS  Google Scholar 

  • Contreras M et al (2007) Inactivation of the interoceptive insula disrupts drug craving and malaise induced by lithium. Science 318:655–658

    Article  PubMed  CAS  Google Scholar 

  • Cox LS et al (2001) Evaluation of the brief questionnaire of smoking urges (QSU-brief) in laboratory and clinical settings. Nicotine Tob Res 3:7–16

    Article  PubMed  CAS  Google Scholar 

  • Craig AD (2002) How do you feel? Interoception: the sense of the physiological condition of the body. Nat Rev Neurosci 3:655–666

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Craig AD (2010) The sentient self. Brain Struc Func 214(5-6). doi:10.1007/s00429-010-0248-y (this issue)

  • Critchley HD, Mathias CJ, Dolan RJ (2002) Fear conditioning in humans: the influence of awareness and autonomic arousal on functional neuranatomy. Neuron 33:653–663

    Article  PubMed  CAS  Google Scholar 

  • Crockford DN et al (2005) Cue-induced brain activity in pathological gamblers. Biol Psychiatry 58:787–795

    Article  PubMed  Google Scholar 

  • Cubero I et al (1999) Insular cortex lesions and taste aversion learning: effects of conditioning method and timing of lesion. Brain Res 839:323–330

    Article  PubMed  CAS  Google Scholar 

  • Damasio AR (1994) Descartes’ Error: emotion, reason and the human brain. Putnam and Sons, New York

    Google Scholar 

  • Damasio AR (2000) The Feeling of What Happens: Body and Emotion in the Making of Consciousness. Harcourt, New York

    Google Scholar 

  • Dar R, Frenk H (2002) Nicotine self-administration in animals: a re-evaluation. Addict Res Theory 10:545–579

    Article  Google Scholar 

  • Dar R, Frenk H (2004) Do smokers self-administer pure nicotine? A review of the evidence. Psychopharmacology (Berl) 173:18–26

    Article  CAS  Google Scholar 

  • de Araujo IE et al (2003) Human cortical responses to water in the mouth, and the effects of thirst. J Neurophysiol 90:1865–1876

    Article  PubMed  Google Scholar 

  • Del Parigi A et al (2002) Neuroimaging and obesity: mapping the brain responses to hunger and satiation in humans using positron emission tomography. Ann N Y Acad Sci 967:389–397

    PubMed  Google Scholar 

  • Egan G et al (2003) Neural correlates of the emergence of consciousness of thirst. Proc Natl Acad Sci USA 100:15241–15246

    Article  PubMed  CAS  Google Scholar 

  • Etter JF, Stapleton JA (2006) Nicotine replacement therapy for long-term smoking cessation: a meta-analysis. Tob Control 15:280–285

    Article  PubMed  Google Scholar 

  • Everitt BJ, Robbins TW (2005) Neural systems of reinforcement for drug addiction: from actions to habits to compulsion. Nat Neurosci 8:1481–1489

    Article  PubMed  CAS  Google Scholar 

  • Farrell MJ et al (2006) Unique, common, and interacting cortical correlates of thirst and pain. Proc Natl Acad Sci USA 103:2416–2421

    Article  PubMed  CAS  Google Scholar 

  • Franklin TR et al (2007) Limbic activation to cigarette smoking cues independent of nicotine withdrawal: a perfusion fMRI study. Neuropsychopharmacology 32:2301–2309

    Article  PubMed  CAS  Google Scholar 

  • Garavan H (2010) The insula and drug cravings. Brain Struc Func 214(5-6). doi:10.1007/s00429-010-0259-8 (this issue)

  • Garavan H et al (2000) Cue-induced cocaine craving: neuroanatomical specificity for drug users and drug stimuli. Am J Psychiatry 157:1789–1798

    Article  PubMed  CAS  Google Scholar 

  • Georgiadis JR et al (2005) Human brain activation during sexual stimulation of the penis. J Comp Neurol 493:33–38

    Article  PubMed  Google Scholar 

  • Goldstein RZ et al (2009) The neurocircuitry of impaired insight in drug addiction. Trends Cogn Sci 13:372–380

    Article  PubMed  Google Scholar 

  • Gowing L et al (2004) Alpha2 adrenergic agonists for the management of opioid withdrawal [update in Cochrane Database Syst Rev. 2009;(2):CD002024; PMID: 19370574][update of Cochrane Database Syst Rev. 2003;(2):CD002024; PMID: 12804419]. Cochrane Database Syst Rev (4):CD002024

  • Heatherton TF et al (1991) The Fagerstrom Test for nicotine dependence: a revision of the Fagerstrom Tolerance Questionnaire. Br J Addict 86:1119–1127

    Article  PubMed  CAS  Google Scholar 

  • Hudmon KS et al (2005) Validity of retrospective assessments of nicotine dependence: a preliminary report. Addict Behav 30:613–617

    Article  PubMed  Google Scholar 

  • Hurd YL et al (2001) D1 and D2 dopamine receptor mRNA expression in whole hemisphere sections of the human brain. J Chem Neuroanat 22:127–137

    Article  PubMed  CAS  Google Scholar 

  • Hurley KM et al (1991) Efferent projections of the infralimbic cortex of the rat. J Comp Neurol 308:249–276

    Article  PubMed  CAS  Google Scholar 

  • Ibanez A, Ezequiel G, Manes F (2010) Clinical effects of insular damage in humans. Brain Struc Func 214(5-6). doi:10.1007/s00429-010-0256-y (this issue)

  • James W (1884) What is an emotion? Mind 9:188–205

    Article  Google Scholar 

  • Kampman KM et al (2001) Effectiveness of propranolol for cocaine dependence treatment may depend on cocaine withdrawal symptom severity. Drug Alcohol Depend 63:69–78

    Article  PubMed  CAS  Google Scholar 

  • Karama S et al (2002) Areas of brain activation in males and females during viewing of erotic film excerpts. Hum Brain Mapp 16:1–13

    Article  PubMed  Google Scholar 

  • Kilts CD et al (2004) The neural correlates of cue-induced craving in cocaine-dependent women. Am J Psychiatry 161:233–241

    Article  PubMed  Google Scholar 

  • Koob GF, Le Moal M (2001) Drug addiction, dysregulation of reward, and allostasis. Neuropsychopharmacology 24:97–129

    Article  PubMed  CAS  Google Scholar 

  • Koob GF et al (2004) Neurobiological mechanisms in the transition from drug use to drug dependence. Neurosci Biobehav Rev 27:739–749

    Article  PubMed  CAS  Google Scholar 

  • Krettek JE, Price JL (1978) Amygdaloid projections to subcortical structures within the basal forebrain and brainstem in the rat and cat. J Comp Neurol 178:225–254

    Article  PubMed  CAS  Google Scholar 

  • Lee JH et al (2005) A functional magnetic resonance imaging (FMRI) study of cue-induced smoking craving in virtual environments. Appl Psychophysiol Biofeedback 30:195–204

    Article  PubMed  Google Scholar 

  • Levin ED et al (1993) Clinical trials using ascorbic acid aerosol to aid smoking cessation. Drug Alcohol Depend 33:211–223

    Article  PubMed  CAS  Google Scholar 

  • Lovero KL et al (2009) Anterior insular cortex anticipates impending stimulus significance. Neuroimage 45:976–983

    Article  PubMed  Google Scholar 

  • Manes F et al (1999) Neuropsychiatric effects of insular stroke. J Nerv Ment Dis 187:707–712

    Article  PubMed  CAS  Google Scholar 

  • McBride D et al (2006) Effects of expectancy and abstinence on the neural response to smoking cues in cigarette smokers: an fMRI study. Neuropsychopharmacology 31:2728–2738

    Article  PubMed  CAS  Google Scholar 

  • McClernon FJ et al (2005) Abstinence-induced changes in self-report craving correlate with event-related FMRI responses to smoking cues. Neuropsychopharmacology 30:1940–1947

    Article  PubMed  Google Scholar 

  • Medford N, Critchley HD (2010) Conjoint activity of anterior insular and anterior cingulate cortex: awareness and response. Brain Struc Func 214(5-6). doi:10.1007/s00429-010-0265-x (this issue)

  • Morecraft RJ et al (1992) Cytoarchitecture and neural afferents of orbitofrontal cortex in the brain of the monkey. J Comp Neurol 323:341–358

    Article  PubMed  CAS  Google Scholar 

  • Myrick H et al (2004) Differential brain activity in alcoholics and social drinkers to alcohol cues: relationship to craving. Neuropsychopharmacology 29:393–402

    Article  PubMed  CAS  Google Scholar 

  • Naqvi NH (2006) The effects of lesions in the ventromedial prefrontal cortex and related areas on emotional responses to cigarette smoking. Neuroscience 211

  • Naqvi N et al (2006) Visceral and decision-making functions of the ventromedial prefrontal cortex. In: Zald D, Rauch SL (eds) The orbitofrontaol cortex. Oxford University Press, Oxford

  • Naqvi NH, Bechara A (2005) The airway sensory impact of nicotine contributes to the conditioned reinforcing effects of individual puffs from cigarettes. Pharmacol Biochem Behav 81:821–829

    Article  PubMed  CAS  Google Scholar 

  • Naqvi NH et al (2007) Damage to the insula disrupts addiction to cigarette smoking. Science 315:531–534

    Article  PubMed  CAS  Google Scholar 

  • O’Brien CP et al (1998) Conditioning factors in drug abuse: can they explain compulsion? J Psychopharmacol 12:15–22

    Article  PubMed  Google Scholar 

  • Olausson H et al (2002) Unmyelinated tactile afferents signal touch and project to insular cortex. Nat Neurosci 5:900–904

    Article  PubMed  CAS  Google Scholar 

  • Paulozzi LJ (2008) Trends in unintentional drug overdose deaths. In: Judiciary Subcommittee on Crime and Drugs, U.S. Department of Health and Human Services. http://www.hhs.gov/asl/testify/2008/03/t20080312b.html

  • Paulus MP et al (2005) Neural activation patterns of methamphetamine-dependent subjects during decision making predict relapse. Arch Gen Psychiatry 62:761–768

    Article  PubMed  Google Scholar 

  • Pelchat ML et al (2004) Images of desire: food-craving activation during fMRI. Neuroimage 23:1486–1493

    Article  PubMed  Google Scholar 

  • Peto R et al (1992) Mortality from tobacco in developed countries: indirect estimation from national vital statistics. Lancet 339:1268–1278

    Article  PubMed  CAS  Google Scholar 

  • Phan KL et al (2002) Functional neuroanatomy of emotion: a meta-analysis of emotion activation studies in PET and fMRI. Neuroimage 16:331–348

    Article  PubMed  Google Scholar 

  • Potenza MN et al (2003) Gambling urges in pathological gambling: a functional magnetic resonance imaging study. Arch Gen Psychiatry 60:828–836

    Article  PubMed  Google Scholar 

  • Rezaishiraz H et al (2007) Treating smokers before the quit date: Can nicotine patches and denicotinized cigarettes reduce cravings? Nicotine Tob Res 9:1139–1146

    Article  PubMed  Google Scholar 

  • Robinson TE, Berridge KC (2001) Incentive-sensitization and addiction. Addiction 96:103–114

    Article  PubMed  CAS  Google Scholar 

  • Rolls ET, Rolls ET (2005) Taste and related systems in primates including humans. Chem Senses 30(Suppl 1):i76–i77

    Article  PubMed  Google Scholar 

  • Rolls ET, Sienkiewicz ZJ, Yaxley S (1989) Hunger modulates the responses to gustatory stimuli of single neurons in the caudolateral orbitofrontal cortex of the macaque monkey. Eur J Neurosci 1:53–60

    Article  PubMed  Google Scholar 

  • Rose JE, Levin ED (1991) Inter-relationships between conditioned and primary reinforcement in the maintenance of cigarette smoking. Br J Addict 86:605–609

    Article  PubMed  CAS  Google Scholar 

  • Rosenblum K et al (1993) Taste memory: the role of protein synthesis in gustatory cortex. Behav Neural Biol 59:49–56

    Article  PubMed  CAS  Google Scholar 

  • Rosenblum K et al (1995) Modulation of protein tyrosine phosphorylation in rat insular cortex after conditioned taste aversion training. Proc Natl Acad Sci USA 92:1157–1161

    Article  PubMed  CAS  Google Scholar 

  • Sanchez MM et al (1999) Autoradiographic and in situ hybridization localization of corticotropin-releasing factor 1 and 2 receptors in nonhuman primate brain. J Comp Neurol 408:365–377

    Article  PubMed  CAS  Google Scholar 

  • Sehlmeyer C et al (2009) Human fear conditioning and extinction in neuroimaging: a systematic review. PLoS ONE 4:e5865 (electronic resource)

    Google Scholar 

  • Sell LA et al (1999) Activation of reward circuitry in human opiate addicts. Eur J Neurosci 11:1042–1048

    Article  PubMed  CAS  Google Scholar 

  • Small D (2010) Taste representation in the human insula. Brain Struc Func 214(5-6). doi:10.1007/s00429-010-0266-9 (this issue)

  • Spiess M, Fallow D (2000) Drug-Related Crime Report. Retrieved May 11, 2009, from Office of National Drug Control Policy Web site: http://www.whitehousedrugpolicy.gov/publications/factsht/crime/index.html

  • Stinson FS, DeBakey SF (1992) Alcohol-related mortality in the United States, 1979–1988. Br J Addict 87:777–783

    Article  PubMed  CAS  Google Scholar 

  • Stoleru S et al (1999) Neuroanatomical correlates of visually evoked sexual arousal in human males. Arch Sex Behav 28:1–21

    Article  PubMed  CAS  Google Scholar 

  • Tapert SF et al (2004) fMRI BOLD response to alcohol stimuli in alcohol dependent young women. Addict Behav 29:33–50

    Article  PubMed  Google Scholar 

  • Tiffany ST (1990) A cognitive model of drug urges and drug-use behavior: role of automatic and nonautomatic processes. Psychol Rev 97:147–168

    Article  PubMed  CAS  Google Scholar 

  • Tiffany ST (1999) Meta-analysis of cue-reactivity in addiction research. Addiction 94:327–340

    Article  PubMed  Google Scholar 

  • Tiffany ST, Conklin CA (2000) A cognitive processing model of alcohol craving and compulsive alcohol use. Addiction 95(Suppl 2):S145–S153

    PubMed  Google Scholar 

  • Tiffany ST et al (2000) Effects of transdermal nicotine patches on abstinence-induced and cue-elicited craving in cigarette smokers. J Consult Clin Psychol 68:233–240

    Article  PubMed  CAS  Google Scholar 

  • Vorel SR et al (2007) Insula damage and quitting smoking. Science 317:318–319 author reply 318-319

    Article  PubMed  CAS  Google Scholar 

  • Wang GJ et al (1999) Regional brain metabolic activation during craving elicited by recall of previous drug experiences. Life Sciences 64:775–784

    Article  PubMed  CAS  Google Scholar 

  • Wang GJ et al (2004) Exposure to appetitive food stimuli markedly activates the human brain. Neuroimage 21:1790–1797

    Article  PubMed  Google Scholar 

  • Wang Z et al (2007) Neural substrates of abstinence-induced cigarette cravings in chronic smokers. J Neurosci 27:14035–14040

    Article  PubMed  CAS  Google Scholar 

  • Wang GJ et al (2008) Gastric distention activates satiety circuitry in the human brain. Neuroimage 39:1824–1831

    Article  PubMed  Google Scholar 

  • Westman EC et al (1995) Airway sensory replacement combined with nicotine replacement for smoking cessation. A randomized, placebo-controlled trial using a citric acid inhaler. Chest 107:1358–1364

    Article  PubMed  CAS  Google Scholar 

  • Westman EC et al (1996) Dissociating the nicotine and airway sensory effects of smoking. Pharmacol Biochem Behav 53:309–315

    Article  PubMed  CAS  Google Scholar 

  • Wexler BE et al (2001) Functional magnetic resonance imaging of cocaine craving. Am J Psychiatry 158:86–95

    Article  PubMed  CAS  Google Scholar 

  • Wikler A (1948) Recent progress in research on the neurophysiological basis of morphine addiction. Am J Psychiatry 105:329–338

    PubMed  CAS  Google Scholar 

  • Wise RA, Bozarth MA (1987) A psychomotor stimulant theory of addiction. Psychol Rev 94:469–492

    Article  PubMed  CAS  Google Scholar 

  • Yaxley S et al (1988) The responsiveness of neurons in the insular gustatory cortex of the macaque monkey is independent of hunger. Physiol Behav 42:223–229

    Article  PubMed  CAS  Google Scholar 

  • Zito KA et al (1988) The dopamine innervation of the visceral cortex mediates the aversive effects of opiates. Pharmacol Biochem Behav 30:693–699

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The research described in this article was supported by a grant from the National Institute on Drug Abuse (NIDA) R01 DA023051 (A.B.). The writing of this article was supported by grants from the National Institute of Mental Health (NIMH) R25 MH086466 (N.H.N.), and by the Leon Levy Resident Fellowship (N.H.N.).

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Correspondence to Nasir H. Naqvi.

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Naqvi, N.H., Bechara, A. The insula and drug addiction: an interoceptive view of pleasure, urges, and decision-making. Brain Struct Funct 214, 435–450 (2010). https://doi.org/10.1007/s00429-010-0268-7

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