Cognitive, Affective, & Behavioral Neuroscience

, Volume 14, Issue 4, pp 1196–1207 | Cite as

Weak ventral striatal responses to monetary outcomes predict an unwillingness to resist cigarette smoking

  • Stephen J. Wilson
  • Mauricio R. Delgado
  • Sherry A. McKee
  • Patricia S. Grigson
  • R. Ross MacLean
  • Travis T. Nichols
  • Shannon L. Henry
Article

Abstract

As a group, cigarette smokers exhibit blunted subjective, behavioral, and neurobiological responses to nondrug incentives and rewards, relative to nonsmokers. Findings from recent studies suggest, however, that there are large individual differences in the devaluation of nondrug rewards among smokers. Moreover, this variability appears to have significant clinical implications, since reduced sensitivity to nondrug rewards is associated with poorer smoking cessation outcomes. Currently, little is known about the neurobiological mechanisms that underlie these individual differences in the responsiveness to nondrug rewards. Here, we tested the hypothesis that individual variability in reward devaluation among smokers is linked to the functioning of the striatum. Specifically, functional magnetic resonance imaging was used to examine variability in the neural response to monetary outcomes in nicotine-deprived smokers anticipating an opportunity to smoke—circumstances found to heighten the devaluation of nondrug rewards by smokers in prior work. We also investigated whether individual differences in reward-related brain activity in those expecting to have access to cigarettes were associated with the degree to which the same individuals subsequently were willing to resist smoking in order to earn additional money. Our key finding was that deprived smokers who exhibited the weakest response to rewards (i.e., monetary gains) in the ventral striatum were least willing to refrain from smoking for monetary reinforcement. These results provide evidence that outcome-related signals in the ventral striatum serve as a marker for clinically meaningful individual differences in reward-motivated behavior among nicotine-deprived smokers.

Keywords

fMRI Individual differences Relapse Reward Smoking Striatum 

Notes

Acknowledgments

Funding for this study was provided by NIDA Grant R03DA029675. Dr. Wilson’s research is supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health under BIRCWH award number K12HD055882, “Career Development Program in Women’s Health Research at Penn State.” The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. We thank Theresa McKim and the staff of the Penn State Smoking Research Lab for their assistance with data collection.

References

  1. al-Adawi, S., & Powell, J. (1997). The influence of smoking on reward responsiveness and cognitive functions: A natural experiment. Addiction, 92(12), 1773–1782.PubMedCrossRefGoogle Scholar
  2. Bogdan, R., & Pizzagalli, D. A. (2006). Acute stress reduces reward responsiveness: Implications for depression. Biological Psychiatry, 60(10), 1147–1154. doi: 10.1016/j.biopsych.2006.03.037 PubMedCentralPubMedCrossRefGoogle Scholar
  3. Broos, N., Schmaal, L., Wiskerke, J., Kostelijk, L., Lam, T., Stoop, N., & Goudriaan, A. E. (2012). The relationship between impulsive choice and impulsive action: A cross-species translational study. PloS One, 7(5), e36781. doi: 10.1371/journal.pone.0036781 PubMedCentralPubMedCrossRefGoogle Scholar
  4. Buhler, M., Vollstadt-Klein, S., Kobiella, A., Budde, H., Reed, L. J., Braus, D. F., & Smolka, M. N. (2010). Nicotine dependence is characterized by disordered reward processing in a network driving motivation. Biological Psychiatry, 67(8), 745–752. doi: 10.1016/j.biopsych.2009.10.029 PubMedCrossRefGoogle Scholar
  5. Cohen, J., Cohen, P., West, S. G., & Aiken, L. S. (2003). Applied multiple regression/correlation analysis for the behavioral sciences (3rd ed.). Mahwah, NJ, US: Lawrence Erlbaum Associates Publishers.Google Scholar
  6. Cousijn, J., Wiers, R. W., Ridderinkhof, K. R., van den Brink, W., Veltman, D. J., Porrino, L. J., & Goudriaan, A. E. (2013). Individual differences in decision making and reward processing predict changes in cannabis use: A prospective functional magnetic resonance imaging study. Addiction Biology, 18(6), 1013–1023. doi: 10.1111/j.1369-1600.2012.00498.x PubMedCrossRefGoogle Scholar
  7. Cox, L. S., Tiffany, S. T., & Christen, A. G. (2001). Evaluation of the brief questionnaire of smoking urges (QSU-brief) in laboratory and clinical settings. Nicotine & Tobacco Research, 3(1), 7–16.CrossRefGoogle Scholar
  8. Dagher, A., Bleicher, C., Aston, J. A., Gunn, R. N., Clarke, P. B., & Cumming, P. (2001). Reduced dopamine D1 receptor binding in the ventral striatum of cigarette smokers. Synapse, 42(1), 48–53. doi: 10.1002/syn.1098 PubMedCrossRefGoogle Scholar
  9. Delgado, M. R. (2007). Reward-related responses in the human striatum. Annals of the New York Academy of Sciences, 1104, 70–88. doi: 10.1196/annals.1390.002 PubMedCrossRefGoogle Scholar
  10. Delgado, M. R., Nystrom, L. E., Fissell, C., Noll, D. C., & Fiez, J. A. (2000). Tracking the hemodynamic responses to reward and punishment in the striatum. Journal of Neurophysiology, 84(6), 3072–3077.PubMedGoogle Scholar
  11. Falk, E. B., Berkman, E. T., Whalen, D., & Lieberman, M. D. (2011). Neural activity during health messaging predicts reductions in smoking above and beyond self-report. Health Psychology, 30(2), 177–185. doi: 10.1037/a0022259 PubMedCentralPubMedCrossRefGoogle Scholar
  12. Fareri, D. S., Niznikiewicz, M. A., Lee, V. K., & Delgado, M. R. (2012). Social network modulation of reward-related signals. Journal of Neuroscience, 32(26), 9045–9052. doi: 10.1523/jneurosci.0610-12.2012 PubMedCentralPubMedCrossRefGoogle Scholar
  13. Froeliger, B., Kozink, R. V., Rose, J. E., Behm, F. M., Salley, A. N., & McClernon, F. J. (2010). Hippocampal and striatal gray matter volume are associated with a smoking cessation treatment outcome: Results of an exploratory voxel-based morphometric analysis. Psychopharmacology, 210(4), 577–583. doi: 10.1007/s00213-010-1862-3 PubMedCrossRefGoogle Scholar
  14. George, O., & Koob, G. F. (2010). Individual differences in prefrontal cortex function and the transition from drug use to drug dependence. Neuroscience and Biobehavioral Reviews, 35(2), 232–247. doi: 10.1016/j.neubiorev.2010.05.002 PubMedCentralPubMedCrossRefGoogle Scholar
  15. Gomez, F. (2001). Induction of conditioned taste aversion with a self-administered substance in rats. Brain Research. Brain Research Protocols, 8(2), 137–142.PubMedCrossRefGoogle Scholar
  16. Gomez, F. (2002). Conditioned saccharin aversion induced by self-administered cocaine negatively correlates with the rate of cocaine self-administration in rats. Brain Research, 946(2), 214–220.PubMedCrossRefGoogle Scholar
  17. Grigson, P. S. (1997). Conditioned taste aversions and drugs of abuse: A reinterpretation. Behavioral Neuroscience, 111(1), 129–136.PubMedCrossRefGoogle Scholar
  18. Grigson, P. S., & Hajnal, A. (2007). Once is too much: Conditioned changes in accumbens dopamine following a single saccharin-morphine pairing. Behavioral Neuroscience, 121(6), 1234–1242. doi: 10.1037/0735-7044.121.6.1234 PubMedCrossRefGoogle Scholar
  19. Grigson, P. S., & Twining, R. C. (2002). Cocaine-induced suppression of saccharin intake: A model of drug-induced devaluation of natural rewards. Behavioral Neuroscience, 116(2), 321–333.PubMedCrossRefGoogle Scholar
  20. Grigson, P. S., Twining, R. C., Freet, C. S., Wheeler, R. A., & Geddes, R. I. (2009). Drug-induced suppression of conditioned stimulus intake: Reward, aversion, and addiction. In S. Reilly & T. R. Schachtman (Eds.), Conditioned taste aversion: Behavioral and neural processes. New York: Oxford University Press.Google Scholar
  21. Haber, S. N., & Knutson, B. (2010). The reward circuit: Linking primate anatomy and human imaging. Neuropsychopharmacology, 35(1), 4–26. doi: 10.1038/npp.2009.129 PubMedCentralPubMedCrossRefGoogle Scholar
  22. Hariri, A. R., Brown, S. M., Williamson, D. E., Flory, J. D., de Wit, H., & Manuck, S. B. (2006). Preference for immediate over delayed rewards is associated with magnitude of ventral striatal activity. Journal of Neuroscience, 26(51), 13213–13217. doi: 10.1523/jneurosci.3446-06.2006 PubMedCrossRefGoogle Scholar
  23. Heatherton, T. F., Kozlowski, L. T., Frecker, R. C., & Fagerstrom, K. O. (1991). The fagerstrom test for nicotine dependence: A revision of the fagerstrom tolerance questionnaire. British Journal of Addiction, 86(9), 1119–1127.PubMedCrossRefGoogle Scholar
  24. Hughes, J. R., & Hatsukami, D. K. (1986). Signs and symptoms of tobacco withdrawal. Archives of General Psychiatry, 43(3), 289–294.PubMedCrossRefGoogle Scholar
  25. Hughes, J. R., & Hatsukami, D. K. (1998). Errors in using tobacco withdrawal scale. Tobacco Control, 7(1), 92–93.PubMedCentralPubMedCrossRefGoogle Scholar
  26. Janes, A. C., Pizzagalli, D. A., Richardt, S., deB Frederick, B., Chuzi, S., Pachas, G., & Kaufman, M. J. (2010). Brain reactivity to smoking cues prior to smoking cessation predicts ability to maintain tobacco abstinence. Biological Psychiatry, 67(8), 722–729. doi: 10.1016/j.biopsych.2009.12.034 PubMedCentralPubMedCrossRefGoogle Scholar
  27. Juliano, L. M., & Brandon, T. H. (1998). Reactivity to instructed smoking availability and environmental cues: Evidence with urge and reaction time. Experimental and Clinical Psychopharmacology, 6(1), 45–53.PubMedCrossRefGoogle Scholar
  28. Kalivas, P. W., & Volkow, N. D. (2005). The neural basis of addiction: A pathology of motivation and choice. The American Journal of Psychiatry, 162(8), 1403–1413. doi: 10.1176/appi.ajp.162.8.1403 PubMedCrossRefGoogle Scholar
  29. Kobiella, A., Ripke, S., Kroemer, N. B., Vollmert, C., Vollstadt-Klein, S., Ulshofer, D. E., & Smolka, M. N. (2013). Acute and chronic nicotine effects on behaviour and brain activation during intertemporal decision making. Addiction Biology. doi: 10.1111/adb.12057 Google Scholar
  30. Lam, C. Y., Robinson, J. D., Versace, F., Minnix, J. A., Cui, Y., Carter, B. L., & Cinciripini, P. M. (2012). Affective reactivity during smoking cessation of never-quitters as compared with that of abstainers, relapsers, and continuing smokers. Experimental and Clinical Psychopharmacology, 20(2), 139–150. doi: 10.1037/a0026109 PubMedCentralPubMedCrossRefGoogle Scholar
  31. Lighthall, N. R., Sakaki, M., Vasunilashorn, S., Nga, L., Somayajula, S., Chen, E. Y., & Mather, M. (2012). Gender differences in reward-related decision processing under stress. Social Cognitive and Affective Neuroscience, 7(4), 476–484. doi: 10.1093/scan/nsr026 PubMedCentralPubMedCrossRefGoogle Scholar
  32. Luijten, M., O'Connor, D. A., Rossiter, S., Franken, I. H., & Hester, R. (2013). Effects of reward and punishment on brain activations associated with inhibitory control in cigarette smokers. Addiction. doi: 10.1111/add.12276 PubMedGoogle Scholar
  33. Luo, S., Ainslie, G., Giragosian, L., & Monterosso, J. R. (2011). Striatal hyposensitivity to delayed rewards among cigarette smokers. Drug and Alcohol Dependence, 116(1–3), 18–23. doi: 10.1016/j.drugalcdep.2010.11.012 PubMedCentralPubMedCrossRefGoogle Scholar
  34. MacKillop, J., Amlung, M. T., Wier, L. M., David, S. P., Ray, L. A., Bickel, W. K., & Sweet, L. H. (2012). The neuroeconomics of nicotine dependence: A preliminary functional magnetic resonance imaging study of delay discounting of monetary and cigarette rewards in smokers. Psychiatry Research, 202(1), 20–29. doi: 10.1016/j.pscychresns.2011.10.003 PubMedCentralPubMedCrossRefGoogle Scholar
  35. Martinez, D., Carpenter, K. M., Liu, F., Slifstein, M., Broft, A., Friedman, A. C., & Nunes, E. (2011). Imaging dopamine transmission in cocaine dependence: Link between neurochemistry and response to treatment. The American Journal of Psychiatry, 168(6), 634–641. doi: 10.1176/appi.ajp.2010.10050748 PubMedCentralPubMedCrossRefGoogle Scholar
  36. Martin-Soelch, C., Missimer, J., Leenders, K. L., & Schultz, W. (2003). Neural activity related to the processing of increasing monetary reward in smokers and nonsmokers. European Journal of Neuroscience, 18(3), 680–688.PubMedCrossRefGoogle Scholar
  37. Martin-Solch, C., Magyar, S., Kunig, G., Missimer, J., Schultz, W., & Leenders, K. L. (2001). Changes in brain activation associated with reward processing in smokers and nonsmokers. A positron emission tomography study. Experimental Brain Research, 139(3), 278–286.PubMedCrossRefGoogle Scholar
  38. McKee, S. A. (2009). Developing human laboratory models of smoking lapse behavior for medication screening. Addiction Biology, 14(1), 99–107. doi: 10.1111/j.1369-1600.2008.00135.x PubMedCentralPubMedCrossRefGoogle Scholar
  39. McKee, S. A., Krishnan-Sarin, S., Shi, J., Mase, T., & O'Malley, S. S. (2006). Modeling the effect of alcohol on smoking lapse behavior. Psychopharmacology, 189(2), 201–210. doi: 10.1007/s00213-006-0551-8 PubMedCentralPubMedCrossRefGoogle Scholar
  40. McKee, S. A., Weinberger, A. H., Shi, J., Tetrault, J., & Coppola, S. (2012). Developing and validating a human laboratory model to screen medications for smoking cessation. Nicotine & Tobacco Research. doi: 10.1093/ntr/nts090 Google Scholar
  41. Mueller, E. T., Landes, R. D., Kowal, B. P., Yi, R., Stitzer, M. L., Burnett, C. A., & Bickel, W. K. (2009). Delay of smoking gratification as a laboratory model of relapse: Effects of incentives for not smoking, and relationship with measures of executive function. Behavioral Pharmacology, 20(5–6), 461–473. doi: 10.1097/FBP.0b013e3283305ec7 CrossRefGoogle Scholar
  42. Muller, K. U., Mennigen, E., Ripke, S., Banaschewski, T., Barker, G. J., Buchel, C., . . . Smolka, M. N. (2013). Altered Reward Processing in Adolescents With Prenatal Exposure to Maternal Cigarette Smoking. JAMA Psychiatry, 1-10. doi: 10.1001/jamapsychiatry.2013.44Google Scholar
  43. Nees, F., Witt, S. H., Lourdusamy, A., Vollstadt-Klein, S., Steiner, S., Poustka, L., & Flor, H. (2013). Genetic risk for nicotine dependence in the cholinergic system and activation of the brain reward system in healthy adolescents. Neuropsychopharmacology. doi: 10.1038/npp.2013.131 PubMedCentralGoogle Scholar
  44. O'Doherty, J. P. (2004). Reward representations and reward-related learning in the human brain: Insights from neuroimaging. Current Opinion in Neurobiology, 14(6), 769–776. doi: 10.1016/j.conb.2004.10.016 PubMedCrossRefGoogle Scholar
  45. Ossewaarde, L., Qin, S., Van Marle, H. J., van Wingen, G. A., Fernandez, G., & Hermans, E. J. (2011). Stress-induced reduction in reward-related prefrontal cortex function. NeuroImage, 55(1), 345–352. doi: 10.1016/j.neuroimage.2010.11.068 PubMedCrossRefGoogle Scholar
  46. Peters, J., Bromberg, U., Schneider, S., Brassen, S., Menz, M., Banaschewski, T., & Buchel, C. (2011). Lower ventral striatal activation during reward anticipation in adolescent smokers. The American Journal of Psychiatry, 168(5), 540–549. doi: 10.1176/appi.ajp.2010.10071024 PubMedCrossRefGoogle Scholar
  47. Piasecki, T. M. (2006). Relapse to smoking. Clinical Psychology Review, 26(2), 196–215. doi: 10.1016/j.cpr.2005.11.007 PubMedCrossRefGoogle Scholar
  48. Porcelli, A. J., Lewis, A. H., & Delgado, M. R. (2012). Acute stress influences neural circuits of reward processing. Frontiers in Neuroscience, 6, 157. doi: 10.3389/fnins.2012.00157 PubMedCentralPubMedCrossRefGoogle Scholar
  49. Radloff, L. S. (1977). The CES-D Scale. Applied Psychological Measurement, 1(3), 385–401.CrossRefGoogle Scholar
  50. Rose, E. J., Ross, T. J., Salmeron, B. J., Lee, M., Shakleya, D. M., Huestis, M., & Stein, E. A. (2012). Chronic exposure to nicotine is associated with reduced reward-related activity in the striatum but not the midbrain. Biological Psychiatry, 71(3), 206–213. doi: 10.1016/j.biopsych.2011.09.013 PubMedCentralPubMedCrossRefGoogle Scholar
  51. Sayette, M. A., Loewenstein, G., Griffin, K. M., & Black, J. J. (2008). Exploring the cold-to-hot empathy gap in smokers. Psychological Science, 19(9), 926–932. doi: 10.1111/j.1467-9280.2008.02178.x PubMedCentralPubMedCrossRefGoogle Scholar
  52. Schneider, S., Peters, J., Bromberg, U., Brassen, S., Miedl, S. F., Banaschewski, T., & Buchel, C. (2012). Risk taking and the adolescent reward system: A potential common link to substance abuse. The American Journal of Psychiatry, 169(1), 39–46. doi: 10.1176/appi.ajp.2011.11030489 PubMedCrossRefGoogle Scholar
  53. Schultz, W., Tremblay, L., & Hollerman, J. R. (2000). Reward processing in primate orbitofrontal cortex and basal ganglia. Cerebral Cortex, 10(3), 272–284.PubMedCrossRefGoogle Scholar
  54. Sheehan, D. V., Lecrubier, Y., Sheehan, K. H., Amorim, P., Janavs, J., Weiller, E., & Dunbar, G. C. (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. Journal of Clinical Psychiatry, 59(Suppl 20), 22–57.PubMedGoogle Scholar
  55. Sheffer, C., Mackillop, J., McGeary, J., Landes, R., Carter, L., Yi, R., & Bickel, W. (2012). Delay discounting, locus of control, and cognitive impulsiveness independently predict tobacco dependence treatment outcomes in a highly dependent, lower socioeconomic group of smokers. American Journal on Addictions, 21(3), 221–232. doi: 10.1111/j.1521-0391.2012.00224.x PubMedCentralPubMedCrossRefGoogle Scholar
  56. Stitzer, M., & Petry, N. (2006). Contingency management for treatment of substance abuse. Annual Review of Clinical Psychology, 2, 411–434. doi: 10.1146/annurev.clinpsy.2.022305.095219 PubMedCrossRefGoogle Scholar
  57. Sweitzer, M. M., Donny, E. C., & Hariri, A. R. (2012). Imaging genetics and the neurobiological basis of individual differences in vulnerability to addiction. Drug and Alcohol Dependence, 123(Suppl 1), S59–S71. doi: 10.1016/j.drugalcdep.2012.01.017 PubMedCrossRefGoogle Scholar
  58. Talairach, J., & Tournoux, P. (1988). Co-planar stereotaxic atlas of the human brain: An approach to medical cerebral imaging. Stuttgart, Germany: Thieme.Google Scholar
  59. Twining, R. C., Bolan, M., & Grigson, P. S. (2009). Yoked delivery of cocaine is aversive and protects against the motivation for drug in rats. Behavioral Neuroscience, 123(4), 913–925. doi: 10.1037/a0016498 PubMedCrossRefGoogle Scholar
  60. Versace, F., Lam, C. Y., Engelmann, J. M., Robinson, J. D., Minnix, J. A., Brown, V. L., & Cinciripini, P. M. (2012). Beyond cue reactivity: Blunted brain responses to pleasant stimuli predict long-term smoking abstinence. Addiction Biology, 17(6), 991–1000. doi: 10.1111/j.1369-1600.2011.00372.x PubMedCentralPubMedCrossRefGoogle Scholar
  61. Wang, G. J., Smith, L., Volkow, N. D., Telang, F., Logan, J., Tomasi, D., & Fowler, J. S. (2012). Decreased dopamine activity predicts relapse in methamphetamine abusers. Molecular Psychiatry, 17(9), 918–925. doi: 10.1038/mp.2011.86 PubMedCentralPubMedCrossRefGoogle Scholar
  62. Wheeler, R. A., Aragona, B. J., Fuhrmann, K. A., Jones, J. L., Day, J. J., Cacciapaglia, F., & Carelli, R. M. (2011). Cocaine cues drive opposing context-dependent shifts in reward processing and emotional state. Biological Psychiatry, 69(11), 1067–1074. doi: 10.1016/j.biopsych.2011.02.014 PubMedCentralPubMedCrossRefGoogle Scholar
  63. Wheeler, R. A., Twining, R. C., Jones, J. L., Slater, J. M., Grigson, P. S., & Carelli, R. M. (2008). Behavioral and electrophysiological indices of negative affect predict cocaine self-administration. Neuron, 57(5), 774–785. doi: 10.1016/j.neuron.2008.01.024 PubMedCrossRefGoogle Scholar
  64. Wilson, S. J., Sayette, M. A., Delgado, M. R., & Fiez, J. A. (2005). Instructed smoking expectancy modulates cue-elicited neural activity: A preliminary study. Nicotine and Tobacco Research, 7(4), 637–645.PubMedCentralPubMedCrossRefGoogle Scholar
  65. Wilson, S. J., Sayette, M. A., Delgado, M. R., & Fiez, J. A. (2008). Effect of smoking opportunity on responses to monetary gain and loss in the caudate nucleus. Journal of Abnormal Psychology, 117(2), 428–434. doi: 10.1037/0021-843X.117.2.428 PubMedCentralPubMedCrossRefGoogle Scholar
  66. Wilson, S. J., Sayette, M. A., & Fiez, J. A. (2004). Prefrontal responses to drug cues: A neurocognitive analysis. Nature Neuroscience, 7(3), 211–214.PubMedCentralPubMedCrossRefGoogle Scholar
  67. Wilson, S. J., Sayette, M. A., & Fiez, J. A. (2012). Quitting-unmotivated and quitting-motivated cigarette smokers exhibit different patterns of cue-elicited brain activation when anticipating an opportunity to smoke. Journal of Abnormal Psychology, 121(1), 198–211. doi: 10.1037/a0025112 PubMedCentralPubMedCrossRefGoogle Scholar
  68. Wilson, S. J., Smyth, J. M., & MacLean, R. R. (2014). Integrating ecological momentary assessment and functional brain imaging methods: New avenues for studying and treating tobacco dependence. Nicotine & Tobacco Research doi: 10.1093/ntr/ntt129

Copyright information

© Psychonomic Society, Inc. 2014

Authors and Affiliations

  • Stephen J. Wilson
    • 1
    • 2
    • 6
  • Mauricio R. Delgado
    • 3
  • Sherry A. McKee
    • 4
  • Patricia S. Grigson
    • 5
  • R. Ross MacLean
    • 1
  • Travis T. Nichols
    • 1
  • Shannon L. Henry
    • 1
  1. 1.Department of PsychologyPennsylvania State UniversityUniversity ParkUSA
  2. 2.Center for Brain, Behavior, and CognitionPennsylvania State UniversityUniversity ParkUSA
  3. 3.Department of PsychologyRutgers UniversityNewarkUSA
  4. 4.Department of PsychiatryYale University School of MedicineNew HavenUSA
  5. 5.Department of Neural and Behavioral SciencesPenn State College of MedicineHersheyUSA
  6. 6.Department of PsychologyPennsylvania State UniversityUniversity ParkUSA

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