Brain Imaging and Behavior

, Volume 10, Issue 1, pp 136–146 | Cite as

Brain responses to emotional salience and reward in alcohol use disorder

  • L. Alba-Ferrara
  • E. M. Müller-Oehring
  • E. V. Sullivan
  • A. Pfefferbaum
  • T. Schulte
Original Research


Heightened neural responsiveness of alcoholics to alcohol cues and social emotion may impede sobriety. To test mesocorticolimbic network responsivity, 10 (8 men) alcohol use disorder (AUD) patients sober for 3 weeks to 10 months and 11 (8 men) controls underwent fMRI whilst viewing pictures of alcohol and non-alcohol beverages and of emotional faces (happy, sad, angry). AUD and controls showed similarities in mesocorticolimbic activity: both groups activated fusiform for emotional faces and hippocampal and pallidum regions during alcohol picture processing. In AUD, less fusiform activity to emotional faces and more pallidum activity to alcohol pictures were associated with longer sobriety. Using graph theory-based network efficiency measures to specify the role of the mesocorticolimbic network nodes for emotion and reward in sober AUD revealed that the left hippocampus was less efficiently connected with the other task-activated network regions in AUD than controls when viewing emotional faces, while the pallidum was more efficiently connected when viewing alcohol beverages. Together our findings identified lower occipito-temporal sensitivity to emotional faces and enhanced striatal sensitivity to alcohol stimuli in AUD than controls. Considering the role of the striatum in encoding reward, its activation enhancement with longer sobriety may reflect adaptive neural changes in the first year of drinking cessation and mesocorticolimbic system vulnerability for encoding emotional salience and reward potentially affecting executive control ability and relapse propensity during abstinence.


Alcohol use disorder fMRI Mesocorticolimbic Functional connectivity Emotion Reward Face processing Sobriety 



Support: AA018022, AA010723, AA023165, AA012388, AA017168

Conflict of Interest

Authors Lucia Alba-Ferrara, Eva M. Müller-Oehring, Edith V. Sullivan, Adolf Pfefferbaum, and Tilman Schulte declare that they have no conflict of interest.

Informed Consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all participants for being included in the study.

Supplementary material

11682_2015_9374_MOESM1_ESM.doc (82 kb)
ESM 1 (DOC 82 kb)
11682_2015_9374_MOESM2_ESM.doc (47 kb)
ESM 2 (DOC 47 kb)


  1. Adolphs, R., Damasio, H., Tranel, D., & Damasio, A. (1996). Cortical systems for the recognition of emotion in facial expressions. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 16, 7678–7687.Google Scholar
  2. Alba-Ferrara, L., Hausmann, M., Mitchell, R. L., & Weis, S. (2011). The neural correlates of emotional prosody comprehension: disentangling simple from complex emotion. PloS One, 6, e28701.CrossRefPubMedPubMedCentralGoogle Scholar
  3. American Psychiatric Association (1994). Diagnostic and statistical manual of mental disorders: DSM-IV. 4th ed. Washington (DC): American Psychiatric Association.Google Scholar
  4. Anteraper, S. A., Whitfield-Gabrieli, S., Keil, B., Shannon, S., Gabrieli, J. D., & Triantafyllou, C. (2013). Exploring functional connectivity networks with multichannel brain array coils. Brain Connectivity, 3, 302–315.CrossRefPubMedGoogle Scholar
  5. Baumgartner, T., Lutz, K., Schmidt, C. F., & Jäncke, L. (2006). The emotional power of music: how music enhances the feeling of affective pictures. Brain Research, 1075, 151–164.CrossRefPubMedGoogle Scholar
  6. Becerra, L., Breiter, H., Wise, R., Gonzalez, R., & Borsook, D. (2001). Reward circuitry activation by noxious thermal stimuli. Neuron, 32, 927–946.CrossRefPubMedGoogle Scholar
  7. Berridge, K., & Robinson, T. (1998). What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience? Brain Research. Brain Research Reviews, 28, 309–369.CrossRefPubMedGoogle Scholar
  8. Blum, K., Chen, T. J., Downs, B. W., Bowirrat, A., Waite, R. L., Braverman, E. R., Madigan, M., Oscar-Berman, M., DiNubile, N., Stice, E., Giordano, J., Morse, S., & Gold, M. (2009). Neurogenetics of dopaminergic receptor supersensitivity in activation of brain reward circuitry and relapse: proposing “deprivation-amplification relapse therapy” (DART). Postgraduate Medicine, 121, 176–196.CrossRefPubMedPubMedCentralGoogle Scholar
  9. Brown, S. (1985). Reinforcement expectancies and alcoholism treatment outcome after a one-year follow-up. Journal of Studies on Alcohol, 46, 304–308.CrossRefPubMedGoogle Scholar
  10. Carton, J. S., Kessler, E. A., & Pape, C. L. (1999). Nonverbal decoding skills and relationship well-being in adults. Journal of Nonverbal Behavior, 23, 91–100.CrossRefGoogle Scholar
  11. Castro, D., Berridge, K. (2014). Advances in the neurobiological bases for food‘ liking’ versus‘ wanting’. Physiology & behavior.Google Scholar
  12. Charlet, K., Schlagenhauf, F., Richter, A., Naundorf, K., Dornhof, L., Weinfurtner, C. E., Konig, F., Walaszek, B., Schubert, F., Muller, C. A., Gutwinski, S., Seissinger, A., Schmitz, L., Walter, H., Beck, A., Gallinat, J., Kiefer, F., Heinz, A. (2013). Neural activation during processing of aversive faces predicts treatment outcome in alcoholism. Addict Biol.Google Scholar
  13. Charlet, K., Schlagenhauf, F., Richter, A., Naundorf, K., Dornhof, L., Weinfurtner, C., König, F., Walaszek, B., Schubert, F., & Müller, C. (2014). Neural activation during processing of aversive faces predicts treatment outcome in alcoholism. Addiction Biology, 19, 439–451.CrossRefPubMedGoogle Scholar
  14. Christopoulos, G. I., Tobler, P. N., Bossaerts, P., Dolan, R. J., & Schultz, W. (2009). Neural correlates of value, risk, and risk aversion contributing to decision making under risk. Journal of Neuroscience, 29, 12574–12583.CrossRefPubMedPubMedCentralGoogle Scholar
  15. Clark, U., Oscar-Berman, M., Shagrin, B., & Pencina, M. (2007). Alcoholism and judgments of affective stimuli. Neuropsychology, 21, 346–362.CrossRefPubMedPubMedCentralGoogle Scholar
  16. Dager, A. D., Anderson, B. M., Stevens, M. C., Pulido, C., Rosen, R., Jiantonio-Kelly, R. E., Sisante, J. F., Raskin, S. A., Tennen, H., Austad, C. S., Wood, R. M., Fallahi, C. R., & Pearlson, G. D. (2013). Influence of alcohol use and family history of alcoholism on neural response to alcohol cues in college drinkers. Alcoholism: Clinical and Experimental Research, 37(Suppl 1), E161–171.CrossRefGoogle Scholar
  17. Dickter, C. L., Forestell, C. A., Hammett, P. J., Young, C. M. (2013). Relationship between alcohol dependence, escape drinking, and early neural attention to alcohol-related cues. Psychopharmacology (Berl).Google Scholar
  18. Dom, G., Sabbe, B., Hulstijn, W., & van den Brink, W. (2005). Substance use disorders and the orbitofrontal cortex: systematic review of behavioural decision-making and neuroimaging studies. The British Journal of Psychiatry: the Journal of Mental Science, 187, 209–220.CrossRefGoogle Scholar
  19. Flagel, S., Clark, J., Robinson, T., Mayo, L., Czuj, A., Willuhn, I., Akers, C., Clinton, S., Phillips, P., & Akil, H. (2011). A selective role for dopamine in stimulus-reward learning. Nature, 469, 53–57.CrossRefPubMedPubMedCentralGoogle Scholar
  20. Foisy, M.-L., Kornreich, C., Petiau, C., Parez, A., Hanak, C., Verbanck, P., Pelc, I., & Philippot, P. (2007). Impaired emotional facial expression recognition in alcoholics: Are these deficits specific to emotional cues? Psychiatry Research, 150, 33–41.CrossRefPubMedGoogle Scholar
  21. Frigerio, E., Burt, D., Montagne, B., Murray, L., & Perrett, D. (2002). Facial affect perception in alcoholics. Psychiatry Research, 113, 161–171.CrossRefPubMedGoogle Scholar
  22. Friston, K. J., Holmes, A. P., Poline, J., Grasby, P., Williams, S., Frackowiak, R. S., & Turner, R. (1995). Analysis of fMRI time-series revisited. NeuroImage, 2, 45–53.CrossRefPubMedGoogle Scholar
  23. Gallagher, M., McMahan, R., & Schoenbaum, G. (1999). Orbitofrontal cortex and representation of incentive value in associative learning. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 19, 6610–6614.Google Scholar
  24. Gilman, J., Ramchandani, V., Crouss, T., & Hommer, D. (2012). Subjective and neural responses to intravenous alcohol in young adults with light and heavy drinking patterns. Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology, 37, 467–477.CrossRefGoogle Scholar
  25. Gorka, S. M., Fitzgerald, D. A., King, A. C., & Phan, K. L. (2013). Alcohol attenuates amygdala-frontal connectivity during processing social signals in heavy social drinkers: a preliminary pharmaco-fMRI study. Psychopharmacology, 229, 141–154.CrossRefPubMedPubMedCentralGoogle Scholar
  26. Grüsser, S. M., Wrase, J., Klein, S., Hermann, D., Smolka, M. N., Ruf, M., Weber-Fahr, W., Flor, H., Mann, K., & Braus, D. F. (2004). Cue-induced activation of the striatum and medial prefrontal cortex is associated with subsequent relapse in abstinent alcoholics. Psychopharmacology, 175, 296–302.CrossRefPubMedGoogle Scholar
  27. Guyer, A. E., Monk, C. S., McClure-Tone, E. B., Nelson, E. E., Roberson-Nay, R., Adler, A. D., Fromm, S. J., Leibenluft, E., Pine, D. S., & Ernst, M. (2008). A developmental examination of amygdala response to facial expressions. Journal of Cognitive Neuroscience, 20, 1565–1582.CrossRefPubMedPubMedCentralGoogle Scholar
  28. Haber, S. N. (2011). Neuroanatomy of reward: A view from the ventral striatum. In J. Gottfried (Ed.), Neurobiology of sensation and reward. Boca Raton: CRC Press.Google Scholar
  29. Heinz, A., Siessmeier, T., Wrase, J., Hermann, D., Klein, S., Grüsser, S., Flor, H., Braus, D., Buchholz, H., & Gründer, G. (2004). Correlation between dopamine D (2) receptors in the ventral striatum and central processing of alcohol cues and craving. The American Journal of Psychiatry, 161, 1783–1789.CrossRefPubMedGoogle Scholar
  30. Hollingshead, A. B., & Redlich, F. C. (1958). Social class and mental illness: Community study. New York: Wiley.CrossRefGoogle Scholar
  31. Hosseini, S. M., Hoeft, F., & Kesler, S. R. (2012). GAT: a graph-theoretical analysis toolbox for analyzing between-group differences in large-scale structural and functional brain networks. PloS One, 7, e40709.CrossRefPubMedPubMedCentralGoogle Scholar
  32. Houben, K., & Wiers, R. W. (2006). Assessing implicit alcohol associations with the implicit association test: fact or artifact? Addictive Behaviors, 31, 1346–1362.CrossRefPubMedGoogle Scholar
  33. Hyman, S., Malenka, R., & Nestler, E. (2006). Neural mechanisms of addiction: the role of reward-related learning and memory. Annual Review of Neuroscience, 29, 565–598.CrossRefPubMedGoogle Scholar
  34. Kim, H., Shimojo, S., & O’Doherty, J. (2006). Is avoiding an aversive outcome rewarding? neural substrates of avoidance learning in the human brain. PLoS Biology, 4, e233.CrossRefPubMedPubMedCentralGoogle Scholar
  35. Kuhn, S., & Gallinat, J. (2011). Common biology of craving across legal and illegal drugs - a quantitative meta-analysis of cue-reactivity brain response. European Journal of Neuroscience, 33, 1318–1326.CrossRefPubMedGoogle Scholar
  36. Lee, S., Lee, E., Ku, J., Yoon, K. J., Namkoong, K., & Jung, Y. C. (2013). Disruption of orbitofronto-striatal functional connectivity underlies maladaptive persistent behaviors in alcohol-dependent patients. Psychiatry Investig, 10, 266–272.CrossRefPubMedPubMedCentralGoogle Scholar
  37. Love, A., James, D., Willner, P. (1998). A comparison of two alcohol craving questionnaires. Addiction (Abingdon, England) 93:1091–1102.Google Scholar
  38. Marinkovic, K., Oscar-Berman, M., Urban, T., O’Reilly, C. E., Howard, J. A., Sawyer, K., & Harris, G. J. (2009). Alcoholism and dampened temporal limbic activation to emotional faces. Alcoholism: Clinical and Experimental Research, 33, 1880–1892.CrossRefGoogle Scholar
  39. Maurage, P., Campanella, S., Philippot, P., Martin, S., & De Timary, P. (2008). Face processing in chronic alcoholism: a specific deficit for emotional features. Alcoholism: Clinical and Experimental Research, 32, 600–606.CrossRefGoogle Scholar
  40. Maurage, P., Grynberg, D., Noel, X., Joassin, F., Hanak, C., Verbanck, P., Luminet, O., de Timary, P., Campanella, S., & Philippot, P. (2011). The “reading the mind in the eyes” test as a new way to explore complex emotions decoding in alcohol dependence. Psychiatry Research, 190, 375–378.CrossRefPubMedGoogle Scholar
  41. Montagne, B., Kessels, R. P., Wester, A. J., & de Haan, E. H. (2006). Processing of emotional facial expressions in Korsakoff’s syndrome. Cortex, 42, 705–710.CrossRefPubMedGoogle Scholar
  42. Müller-Oehring, E. M., Jung, Y. C., Sullivan, E. V., Hawkes, W. C., Pfefferbaum, A., & Schulte, T. (2013). Midbrain-driven emotion and reward processing in alcoholism. Neuropsychopharmacology, 38, 1844–1853.CrossRefPubMedPubMedCentralGoogle Scholar
  43. Müller-Oehring, E., Jung, Y., Pfefferbaum, A., Sullivan, E., Schulte, T. (2014). The Resting Brain of Alcoholics. Cerebral cortex.Google Scholar
  44. Nakano, I. (1998). The limbic system: an outline and brief history of its concept. Neuropathology, 18, 211–214.CrossRefGoogle Scholar
  45. Nichols, T., Brett, M., Andersson, J., Wager, T., & Poline, J.-B. (2005). Valid conjunction inference with the minimum statistic. NeuroImage, 25, 653–660.CrossRefPubMedGoogle Scholar
  46. Noel, X., Van der Linden, M., d’Acremont, M., Bechara, A., Dan, B., Hanak, C., & Verbanck, P. (2007). Alcohol cues increase cognitive impulsivity in individuals with alcoholism. Psychopharmacology, 192, 291–298.CrossRefPubMedGoogle Scholar
  47. Oberlin, B., Dzemidzic, M., Tran, S., Soeurt, C., Albrecht, D., Yoder, K., & Kareken, D. (2013). Beer flavor provokes striatal dopamine release in male drinkers: mediation by family history of alcoholism. Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology, 38, 1617–1624.CrossRefGoogle Scholar
  48. O’Daly, O. G., Trick, L., Scaife, J., Marshall, J., Ball, D., Phillips, M. L., Williams, S. S., Stephens, D. N., & Duka, T. (2012). Withdrawal-associated increases and decreases in functional neural connectivity associated with altered emotional regulation in alcoholism. Neuropsychopharmacology, 37, 2267–2276.CrossRefPubMedPubMedCentralGoogle Scholar
  49. Oscar-Berman, M., Hancock, M., Mildworf, B., Hutner, N., & Weber, D. (1990). Emotional perception and memory in alcoholism and aging. Alcoholism, Clinical and Experimental Research, 14, 383–393.CrossRefPubMedGoogle Scholar
  50. Papez, J. (1937). A proposed mechanism of emotion. Archives of Neurology & Psychiatry, 38, 211–214.CrossRefGoogle Scholar
  51. Philippot, P., Kornreich, C., Blairy, S., Baert, I., Den Dulk, A., Le Bon, O., Streel, E., Hess, U., Pelc, I., & Verbanck, P. (1999). Alcoholics’ deficits in the decoding of emotional facial expression. Alcoholism, Clinical and Experimental Research, 23, 1031–1038.PubMedGoogle Scholar
  52. Rather, B. C., & Sherman, M. F. (1989). Relationship between alcohol expectancies and length of abstinence among alcoholics anonymous members. Addictive Behaviors, 14, 531–536.CrossRefPubMedGoogle Scholar
  53. Rosenbloom, M. J., Pfefferbaum, A., & Sullivan, E. V. (2004). Recovery of short-term memory and psychomotor speed but not postural stability with long-term sobriety in alcoholic women. Neuropsychology, 18, 589–597.CrossRefPubMedGoogle Scholar
  54. Schmidt, K., Nolte-Zenker, B., Patzer, J., Bauer, M., Schmidt, L. G., & Heinz, A. (2001). Psychopathological correlates of reduced dopamine receptor sensitivity in depression, schizophrenia, and opiate and alcohol dependence. Pharmacopsychiatry, 34, 66–72.CrossRefPubMedGoogle Scholar
  55. Singleton, E., Tiffany, S., Henningfield, J. (1994). The multidimensional aspects of craving for alcohol. Unpublished research, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD.Google Scholar
  56. Smith, K. S., Tindell, A. J., Aldridge, J. W., & Berridge, K. C. (2009). Ventral pallidum roles in reward and motivation. Behavioural Brain Research, 196, 155–167.CrossRefPubMedPubMedCentralGoogle Scholar
  57. Smith, E., Weinberg, A., Moran, T., & Hajcak, G. (2013). Electrocortical responses to NIMSTIM facial expressions of emotion. International Journal of Psychophysiology, 88, 17–25.CrossRefPubMedGoogle Scholar
  58. Starcke, K., Holst, R. J., Brink, W., Veltman, D. J., Goudriaan, A. E. (2013). Physiological and Endocrine Reactions to Psychosocial Stress in Alcohol Use Disorders: Duration of Abstinence Matters. Alcoholism: Clinical and Experimental Research.Google Scholar
  59. Tachibana, Y., & Hikosaka, O. (2012). The primate ventral pallidum encodes expected reward value and regulates motor action. Neuron, 76, 826–837.CrossRefPubMedPubMedCentralGoogle Scholar
  60. Tanabe, J., Tregellas, J., Dalwani, M., Thompson, L., Owens, E., Crowley, T., & Banich, M. (2009). Medial orbitofrontal cortex gray matter is reduced in abstinent substance-dependent individuals. Biological Psychiatry, 65, 160–164.CrossRefPubMedPubMedCentralGoogle Scholar
  61. Townshend, J., & Duka, T. (2003). Mixed emotions: alcoholics’ impairments in the recognition of specific emotional facial expressions. Neuropsychologia, 41, 773–782.CrossRefPubMedGoogle Scholar
  62. Vanderschuren, L., & Pierce, R. (2010). Sensitization processes in drug addiction. Current Topics in Behavioral Neurosciences, 3, 179–195.CrossRefPubMedGoogle Scholar
  63. Volkow, N., & Li, T. (2004). Drug addiction: the neurobiology of behaviour gone awry. Nature Reviews Neuroscience, 5, 963–970.CrossRefPubMedGoogle Scholar
  64. Vollstädt-Klein, S., Wichert, S., Rabinstein, J., Bühler, M., Klein, O., Ende, G., Hermann, D., & Mann, K. (2010). Initial, habitual and compulsive alcohol use is characterized by a shift of cue processing from ventral to dorsal striatum. Addiction (Abingdon, England), 105, 1741–1749.CrossRefGoogle Scholar
  65. Vollstädt‐Klein, S., Loeber, S., Richter, A., Kirsch, M., Bach, P., Von der Goltz, C., Hermann, D., Mann, K., & Kiefer, F. (2012). Validating incentive salience with functional magnetic resonance imaging: association between mesolimbic cue reactivity and attentional bias in alcohol‐dependent patients. Addiction Biology, 17, 807–816.CrossRefPubMedGoogle Scholar
  66. Volman, S. F., Lammel, S., Margolis, E. B., Kim, Y., Richard, J. M., Roitman, M. F., & Lobo, M. K. (2013). New insights into the specificity and plasticity of reward and aversion encoding in the mesolimbic system. The Journal of neuroscience: The Official Journal of the Society for Neuroscience, 33, 17569–17576.CrossRefGoogle Scholar
  67. Wallis, J. D. (2007). Orbitofrontal cortex and its contribution to decision-making. Annual Review of Neuroscience, 30, 31–56.CrossRefPubMedGoogle Scholar
  68. Whitfield-Gabrieli, S., & Nieto-Castanon, A. (2012). Conn: a functional connectivity toolbox for correlated and anticorrelated brain networks. Brain Connectivity, 2, 125–141.CrossRefPubMedGoogle Scholar
  69. Yang, H., Devous, M. D., Briggs, R. W., Spence, J. S., Xiao, H., Kreyling, N., & Adinoff, B. (2013). Altered neural processing of threat in alcohol-dependent Men. Alcoholism: Clinical and Experimental Research, 37, 2029–2038.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • L. Alba-Ferrara
    • 1
    • 2
  • E. M. Müller-Oehring
    • 2
    • 3
  • E. V. Sullivan
    • 3
  • A. Pfefferbaum
    • 2
    • 3
  • T. Schulte
    • 2
    • 4
  1. 1.Instituto San Lazaro De NeurocienciasNational Scientific and Technical Research Council (CONICET)Buenos AiresArgentina
  2. 2.Bioscience Division, Neuroscience ProgramSRI InternationalMenlo ParkUSA
  3. 3.Department of Psychiatry & Behavioral SciencesStanford University School of MedicineStanfordUSA
  4. 4.Palo Alto University, Pacific Gradualte School of PsychologyPalo AltoUSA

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