, Volume 229, Issue 1, pp 141–154 | Cite as

Alcohol attenuates amygdala–frontal connectivity during processing social signals in heavy social drinkers

A preliminary pharmaco-fMRI study
  • Stephanie M. Gorka
  • Daniel A. Fitzgerald
  • Andrea C. King
  • K. Luan PhanEmail author
Original Investigation



Convergent evidence shows that alcohol exerts its effects on social behavior via modulation of amygdala reactivity to affective stimuli. Given that affective processing involves dynamic interactions between the amygdala and the prefrontal cortex (PFC), alcohol’s effects are likely to extend beyond regional changes in brain activity to changes that manifest on a broader functional circuit level.


The current study examines alcohol’s effects on functional connectivity (i.e., "coupling") between the amygdala and the PFC during the processing of socio-emotional stimuli using functional magnetic resonance imaging (fMRI).


In a randomized, double blind, placebo-controlled, within-subjects cross-over design, 12 heavy, social drinkers performed an fMRI task designed to probe amygdala response to socio-emotional stimuli (angry, fearful, and happy faces) following acute ingestion of alcohol or placebo. Functional connectivity between the amygdala and PFC was examined and compared between alcohol and placebo sessions using a conventional generalized psychophysiological interaction (gPPI) analysis.


Relative to placebo, alcohol reduced functional coupling between the amygdala and the right orbitofrontal cortex (OFC) during processing of both angry and fearful faces. Alcohol also reduced functional coupling between the amygdala and left OFC during processing of happy faces.


These preliminary findings suggest that alcohol’s effects on social behavior may be mediated by alternations in functional connectivity between the amygdala and OFC during processing of emotional faces.


Alcohol Amygdala Functional connectivity Social threat 



This study was supported by a Brain Research Foundation Grant awarded to ACK and KLP.

Conflicts of interest

All authors declare that they have no conflicts of interest.


  1. Arce E, Miller DA, Feinstein JS, Stein MB, Paulus MP (2006) Lorazepam dose-dependently decreases risk-taking related activation in limbic areas. Psychopharmacology (Berl) 189:105–116. doi: 10.1007/s00213-006-0519-8 CrossRefGoogle Scholar
  2. Adolphs R (2002) Neural systems for recognizing emotion. J Neurosci 12:169–77. doi: 10.1016/S0959-4388(02)00301-X Google Scholar
  3. Amaral DG, Price JL (1984) Amygdala-cortical projections in the monkey (Macaca fascicularis). J Comp Neurol 230:465–96PubMedCrossRefGoogle Scholar
  4. Armeli S, Tennen H, Todd M, Carney MA, Mohr C, Affleck G, Hromi A (2003) A daily process examination of the stress-response dampening effects of alcohol consumption. Psychol Addict Behav 17:266–276. doi: 10.1037/0893-164X.17.4.266 PubMedCrossRefGoogle Scholar
  5. 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. doi: 10.1037/0033-295X.111.1.33 PubMedCrossRefGoogle Scholar
  6. Banks SJ, Eddy KT, Angstadt M, Nathan PJ, Phan KL (2007) Amygdala–frontal connectivity during emotion regulation. Soc Cog Affect Neur 2:303–312. doi: 10.1093/scan/nsm029 CrossRefGoogle Scholar
  7. Babor TF, de la Fuente JR, Saunders J, Grant M (1989) The Alcohol Use Identification Test: guidelines for use in primary health care. World Health Organization, GenevaGoogle Scholar
  8. Barceló F, Suwazono S, Knight RT (2000) Prefrontal modulation of visual processing in humans. Nat Neurosci 3:399–403PubMedCrossRefGoogle Scholar
  9. Beauregard M, Levesque J, Bourgouin P (2001) Neural correlates of conscious self-regulation of emotion. J Neurosci 21:6993–7000Google Scholar
  10. Bechara A, Damasio H, Damasio A (2000) Emotion, decision making and the orbitofrontal cortex. Cereb Cortex 10:295–307. doi: 10.1093/cercor/10.3.295 PubMedCrossRefGoogle Scholar
  11. Beck AX, Ward CH, Mendelson M, Mock J, Erbaugh J (1961) An inventory for measuring depression. Arch Gen Psychiat 4:561–571PubMedCrossRefGoogle Scholar
  12. Beer JS, Heerey EH, Keltner D, Scabini D, Knight RT (2003) The regulatory function of self-conscious emotion: insights from patients with orbitofrontal damage. J Pers Soc Psychol 85:594–604. doi: 10.1037/0022-3514.85.4.594 PubMedCrossRefGoogle Scholar
  13. Blackmon K, Barr WB, Carlson C, Devinsky O, Dubois J, Pogash D et al (2011) Structural evidence for involvement of a left amygdala–orbitofrontal network in subclinical anxiety. Psychiat Res 194:296–303. doi: 10.1016/j.pscychresns.2011.05.007 CrossRefGoogle Scholar
  14. Blair RJ (2003) Neurobiological basis of psychopathy. Brit J Psychiat 182:5–7. doi: 10.1192/bjp.182.1.5 PubMedCrossRefGoogle Scholar
  15. Blair RJ, Morris JS, Frith CD, Perrett DI, Dolan RJ (1999) Dissociable neural responses to facial expressions of sadness and anger. Brain 122:883–893. doi: 10.1093/brain/122.5.883 PubMedCrossRefGoogle Scholar
  16. Buck KJ (1996) Molecular genetic analysis of the role of GABAergic systems in the behavioral and cellular actions of alcohol. Behav Genet 26:313–323PubMedCrossRefGoogle Scholar
  17. Burian SE, Liguori A, Robinson JH (2002) Effects of alcohol on risk-taking during simulated driving. Hum Psychopharm Clin 17:141–150. doi: 10.1002/hup.384 CrossRefGoogle Scholar
  18. Bushman BJ, Cooper HM (1990) Effects of alcohol on human aggression: An integrative research review. Psychol Bull 107:341–354. doi: 10.1037/0033-2909.107.3.341 PubMedCrossRefGoogle Scholar
  19. Chanraud S, Pitel AL, Pfefferbaum A, Sullivan EV (2011) Disruption of functional connectivity of the default-mode network in alcoholism. Cereb Cortex 21:2272–2281. doi: 10.1093/cercor/bhq297 PubMedCrossRefGoogle Scholar
  20. Chastain G (2006) Alcohol, neurotransmitter systems, and behavior. J Gen Psychol 133:329–335. doi: 10.3200/GENP.133.4.329-335 PubMedCrossRefGoogle Scholar
  21. Chawla D, Rees G, Friston KJ (1999) The physiological basis of attentional modulation in extrastriate visual areas. Nat Neurosci 2:671–676PubMedCrossRefGoogle Scholar
  22. Chermack S, Giancola P (1997) The relationship between alcohol and aggression: an integrated biopsychosocial approach. Clin Psychol Rev 6:621–649. doi: 10.1016/S0272-7358(97)00038-X CrossRefGoogle Scholar
  23. Conrad M, McNamara P, King A (2012) The alternative substance paradigm: effectiveness of beverage blinding and effects on acute alcohol responses. Exp Clin Psychopharm 20:382–389. doi: 10.1037/a0029261 CrossRefGoogle Scholar
  24. Cooper ML, Frone MR, Russell M, Mudar P (1995) Drinking to regulate positive and negative emotions: a motivational model of alcohol use. J Pers Soc Psychol 69:990–1005. doi: 10.1037/0022-3514.69.5.990 PubMedCrossRefGoogle Scholar
  25. Courtney KE, Ghahremani DG, Ray LA (2012) Fronto–striatal functional connectivity during response inhibition in alcohol dependence. Addict Biol. doi: 10.1111/adb.12013 PubMedGoogle Scholar
  26. Criswell HE, Breese GR (2005) A conceptualization of integrated actions of ethanol contributing to its GABAmimetic profile: a commentary. Neuropsychopharmacology 30(8):1407–1425. doi: 10.1038/sj.npp.1300750 PubMedCrossRefGoogle Scholar
  27. Curtin JJ, Patrick CJ, Lang AR, Cacioppo JT, Birbaumer N (2001) Alcohol affects emotion through cognition. Psychol Sci 12:527–531. doi: 10.1111/1467-9280.00397 PubMedCrossRefGoogle Scholar
  28. Davidson RJ, Putnam KM, Larson CL (2000) Dysfunction in the neural circuitry of emotion regulation—A possible prelude to violence. Science 289:591–594. doi: 10.1126/science.289.5479.591 PubMedCrossRefGoogle Scholar
  29. de la Mora MP, Cardenas-Cachon L, Vazquez-Garcia M, Crespo-Ramirez M, Jacobsen K, Hoistad M et al (2005) Anxiolytic effects of intra-amygdaloid injection of the D1 antagonist SCH23390 in the rat. Neurosci Lett 377:101–105. doi: 10.1016/j.neulet.2004.11.079 PubMedCrossRefGoogle Scholar
  30. Diaz MR, Chappell AM, Christian DT, Anderson NJ, McCool BA (2011) Dopamine D3-like receptors modulate anxiety-like behavior and regulate GABAergic transmission in the rat lateral/basolateral amygdala. Neuropsychopharmacol 36:1090–1103. doi: 10.1038/npp.2010.246 CrossRefGoogle Scholar
  31. Epstein AM, Sher TG, Young MA, King AC (2007) Tobacco chippers show robust increases in smoking urge after alcohol consumption. Psychopharmacology (Berl) 190:321–329CrossRefGoogle Scholar
  32. First MB, Spitzer RL, Williams JBW, Gibbon M (1995) Structured clinical interview for DSMIV—patient edition (SCID-P). American Psychiatric Press, Washington, DCGoogle Scholar
  33. Forbes CE, Grafman J (2010) The role of the human prefrontal cortex in social cognition and moral judgment. Annu Rev Neurosci 33:299–324. doi: 10.1146/annurev-neuro-060909-153230 PubMedCrossRefGoogle Scholar
  34. Frezza M, di Padova C, Pozzato G, Terpin M, Baraona E, Lieber CS (1990) High blood alcohol levels in women. The role of decreased gastric alcohol dehydrogenase activity and first-pass metabolism. New Engl J Med 322:95–99. doi: 10.1056/NEJM199001113220205 PubMedCrossRefGoogle Scholar
  35. Fridlund AJ (1994) Human facial expression: an evolutionary view. Academic Press, San DiegoGoogle Scholar
  36. Friston KJ, Holmes AP, Poline JB, Grasby PJ, Williams SC, Frackowiak RS, Turner R (1995) Analysis of fMRI time–series revisited. NeuroImage 2:45–53. doi: 10.1006/nimg.1995.1007 PubMedCrossRefGoogle Scholar
  37. Frith CD, Frith U (2007) Social cognition in humans. Curr Biol 17:724–732. doi: 10.1016/j.cub.2007.05.068 CrossRefGoogle Scholar
  38. Fusar-Poli P, Placentino A, Carletti F, Landi P, Allen P, Surguladze S, Benedetti F, Abbamonte M, Gasparotti R, Barale F, Perez J, McGuire P, Politi P (2009) Functional atlas of emotional faces processing: a voxel-based meta-analysis of 105 functional magnetic resonance imaging studies. J Psychiat Neurosci 34:418–32Google Scholar
  39. Gallagher HL, Frith CD (2003) Functional imaging of “theory of mind. Trends Cogn Sci 7:77–83. doi: 10.1016/S1364-6613(02)00025-6 PubMedCrossRefGoogle Scholar
  40. Ghashghaei HT, Barbas H (2002) Pathways for emotion: interactions of prefrontal and anterior temporal pathways in the amygdala of the rhesus monkey. Neuroscience 115:1261–79. doi: 10.1016/S0306-4522(02)00446-3 PubMedCrossRefGoogle Scholar
  41. Ghashghaei HT, Hilgetag CC, Barbas H (2007) Sequence of information processing for emotions based on the anatomic dialogue between prefrontal cortex and amygdala. NeuroImage 34:905–23. doi: 10.1016%2Fj.neuroimage.2006.09.046 PubMedCrossRefGoogle Scholar
  42. Gilman J, Ramchandani V, Crouss T, Hommer D (2011) Subjective and neural responses to intravenous alcohol in young adults with light and heavy drinking patterns. Neuropsychopharmacol 37:467–477. doi: 10.1038/npp.2011.206 CrossRefGoogle Scholar
  43. Gilman J, Ramchandani V, Davis M, Bjork J, Hommer D (2008) Why we like to drink: a functional magnetic resonance imaging study of the rewarding and anxiolytic effects of alcohol. J Neurosci 28:4583–4591. doi: 10.1523/JNEUROSCI.0086-08.2008 PubMedCrossRefGoogle Scholar
  44. Giancola PR, Levinson CA, Corman MD, Godlaski AJ, Morris DH, Phillips JP, Holt JC (2009) Men and women, alcohol and aggression. Exp Clin Psychopharm 17:154–164. doi: 10.1037/a0016385 CrossRefGoogle Scholar
  45. Goldin PR, McRae K, Ramel W, Gross JJ (2008) The neural bases of emotion regulation: reappraisal and suppression of negative emotion. Biol Psychiat 63:577–586. doi: 10.1016%2Fj.biopsych.2007.05.031 PubMedCrossRefGoogle Scholar
  46. Gur RC, Sara R, Hagendoorn M, Marom O, Hughett P, Macy L, Turner T, Bajcsy R, Posner A, Gur RE (2002) A method for obtaining 3-dimensional facial expressions and its standardization for use in neurocognitive studies. J Neurosci Meth 115:137–143. doi: 10.1016/S0165-0270(02)00006-7 CrossRefGoogle Scholar
  47. Han S, Gao X, Humphreys GW, Ge J (2008) Neural processing of threat cues in social environments. Hum Brain Mapp 29(8):945–957. doi: 10.1002/hbm.20439 PubMedCrossRefGoogle Scholar
  48. Harenski CL, Hamann S (2006) Neural correlates of regulating negative emotions related to moral violations. NeuroImage 30:313–324. doi: 10.1016/j.neuroimage.2005.09.034 PubMedCrossRefGoogle Scholar
  49. Hariri AR, Mattay VS, Tessitore A, Fera F, Smith WG, Weinberger DR (2002) Dextroamphetamine modulates the response of the human amygdala. Neuropsychopharmacol 27:1036–1040. doi: 10.1016/S0893-133X(02)00373-1 CrossRefGoogle Scholar
  50. Hariri AR, Mattay VS, Tessitore A, Fera F, Weinberger DR (2003) Neocortical modulation of amygdala response to fearful stimuli. Biol Psychiat 53:494–501. doi: 10.1016/S0006-3223(02)01786-9 PubMedCrossRefGoogle Scholar
  51. Hefner KR, Curtin JJ (2012) Alcohol stress response dampening: selective reduction of anxiety in the face of uncertain threat. J Psychopharmacol 26:232–244. doi: 10.1177/0269881111416691 PubMedCrossRefGoogle Scholar
  52. Holmes AP, Friston KJ (1998) Generalisability, random effects and population inference. Neuroimage: Abstracts of the Fourth International Conference on Functional Mapping of the Human Brain 7:S754Google Scholar
  53. Hull JG (1987) Self-awareness model. In: Blane HT, Leonard KE (eds) Psychological theories of drinking and alcoholism. Guilford Press, New York, pp 272–304Google Scholar
  54. Hyytiä P, Koob GF (1995) GABAA receptor antagonism in the extended amygdala decreases ethanol self-administration in rats. Eur J Pharmacol 283(1):151–159. doi: 10.1016/0014-2999(95)00314-B PubMedCrossRefGoogle Scholar
  55. Iidaka T, Harada T, Sadato N (2011) Forming a negative impression of another person correlates with activation in medial prefrontal cortex and amygdala. Soc Cogn Affect Neurosci 6:516–525. doi: 10.1093/scan/nsq072 PubMedCrossRefGoogle Scholar
  56. Kanske P, Heissler J, Schonfelder S, Bongers A, Wessa M (2011) How to regulate emotion? Neural networks for reappraisal and distraction. Cereb Cortex 21:1379–1388. doi: 10.1093/cercor/bhq216 PubMedCrossRefGoogle Scholar
  57. Khantzian EJ (1997) The self-medication hypothesis of substance use disorders: reconsideration and recent applications. Harvard Rev Psychiat 4:231–244CrossRefGoogle Scholar
  58. Kienast T, Hariri AR, Schlagenhauf F, Wrase J, Sterzer P, Buchholz HG, Smolka MN et al (2008) Dopamine in amygdala gates limbic processing of aversive stimuli in humans. Nat Neurosci 11:1381–1382. doi: 10.1038/nn.2222 Google Scholar
  59. Kim SH, Hamann S (2007) Neural correlates of positive and negative emotion regulation. J Cogn Neurosci 19(5):776–98. doi: 10.1162/jocn.2007.19.5.776 PubMedCrossRefGoogle Scholar
  60. King AC, Houle T, de Wit H, Holdstock L, Schuster A (2002) Biphasic alcohol response differs in heavy versus light drinkers. Alcohol Clin Exp Res 26:827–835. doi: 10.1111/j.1530-0277.2002.tb02611.x PubMedCrossRefGoogle Scholar
  61. King AC, McNamara P, Conrad M, Cao D (2009) Alcohol-induced increases in smoking behavior for nicotinized and denicotinized cigarettes in men and women. Psychopharmacology (Berl) 207:107–117. doi: 10.1007/s00213-009-1638-9 CrossRefGoogle Scholar
  62. King A, McNamara P, Angstadt M, Phan KL (2010) Neural substrates of alcohol induced smoking urge in heavy drinking nondaily smokers. Neuropsychopharmacol 35:692–701. doi: 10.1038/npp.2009.177 CrossRefGoogle Scholar
  63. King AC, de Wit H, McNamara PJ, Cao D (2011) Rewarding, stimulant and sedative alcohol responses and relationship to future binge drinking. Arch Gen Psychiat 68:389–399. doi: 10.1001/archgenpsychiatry.2011.26 PubMedCrossRefGoogle Scholar
  64. Kirsch P, Esslinger C, Chen Q, Mier D, Lis S, Siddhanti S, Gruppe H, Mattay VS, Gallhofer B, Meyer–Lindenberg A (2005) Oxytocin modulates neural circuitry for social cognition and fear in humans. J Neurosci 25:11489–11493. doi: 10.1523/JNEUROSCI.3984-05.2005 PubMedCrossRefGoogle Scholar
  65. Kobiella A, Ulshöfer DE, Vollmert C, Vollstädt–Klein S, Bühler M, Esslinger C, Smolka MN (2010) Nicotine increases neural response to unpleasant stimuli and anxiety in non–smokers. Addict Biol 16:285–295. doi: 10.1111/j.1369-1600.2010.00237.x PubMedCrossRefGoogle Scholar
  66. Koob GF (2003) Neuroadaptive mechanisms of addiction: studies on the extended amygdala. Eur Neuropsychopharm 13:442–452. doi: 10.1016/j.euroneuro.2003.08.005 CrossRefGoogle Scholar
  67. Koob GF (2004) A role for GABA mechanism in the motivational effects of alcohol. Biochem Pharmacol 68:1515–1525. doi: 10.1016/j.bcp.2004.07.031 PubMedCrossRefGoogle Scholar
  68. Kumar S, Porcu P, Werner DF, Matthews DB, Diaz-Granados JL, Helfand RS, Morrow AL (2009) The role of GABA A receptors in the acute and chronic effects of ethanol: a decade of progress. Psychopharmacology 205:529–564. doi: 10.1007/s00213-009-1562-z PubMedCrossRefGoogle Scholar
  69. Kushner MG, Mackenzie TB, Fiszdon J, Valentiner DP, Foa E, Wangensteen D (1996) The effects of alcohol consumption on laboratory induced panic and state anxiety. Arch Gen Psychiat 53:264–270. doi: 10.1001/archpsyc.1996.01830030086013 PubMedCrossRefGoogle Scholar
  70. Labuschagne I, Phan KL, Wood A, Angstadt M, Chua P, Heinrichs M et al (2010) Oxytocin attenuates amygdala reactivity to fear in generalized social anxiety disorder. Neuropsychopharmacol 35:2403–2413. doi: 10.1038/npp.2010.123 CrossRefGoogle Scholar
  71. LeDoux JE (2000) Emotion circuits in the brain. Annu Rev Neurosci 23:155–184. doi: 10.1146/annurev.neuro.23.1.155 PubMedCrossRefGoogle Scholar
  72. Levenson RW, Sher KJ, Grossman LM, Newman J, Newlin DB (1980) Alcohol and stress response dampening: pharmacological effects, expectancy, and tension reduction. J Abnorm Psychol 89:528–538. doi: 10.1037/0021-843X.89.4.528 PubMedCrossRefGoogle Scholar
  73. Lévesque J, Eugène F, Joanette Y, Paquette V, Mensour B, Beaudoin G, Leroux JM, Pierre Bourgouin, Beauregard M (2003) Neural circuitry underlying voluntary suppression of sadness. Biol Psychiat 53:502–510. doi: 10.1016/S0002-3223(03)01817-6
  74. Lieberman MD, Cunningham WA (2009) Type I and Type II error concerns in fMRI research: rebalancing the scale. Soc Cogn Affect Neurosci 4:423–428. doi: 10.1093/scan/nsp052 PubMedCrossRefGoogle Scholar
  75. Marczinski CA, Abroms BD, Van Selst M, Fillmore MT (2005) Alcohol-induced impairment of behavioral control: differential effects on engaging vs. disengaging responses. Psychopharmacology 182:452–459. doi: 10.1007/s00213-005-0116-2 PubMedCrossRefGoogle Scholar
  76. Martin CS, Earleywine M, Musty RE, Perrine MW, Swift RM (1993) Development and validation of the biphasic alcohol effects scale. Alcohol Clin Exp Res 17:140–146. doi: 10.1111/j.1530-0277.1993.tb00739.x PubMedCrossRefGoogle Scholar
  77. McLaren D, Ries M, Xu G, Fitzgerald M, Kastman E, Gliori G, Jabbar B, Johnson S (2008) A method for improved sensitivity and flexibility of psychophysiological interactions in event-related fMRI experiments. Annual Meeting of the Organization for Human Brain MappingGoogle Scholar
  78. McLaren DG, Ries ML, Xu G, Johnson SC (2012) A generalized form of context-dependent psychophysiological interactions (gPPI): A comparison to standard approaches. NeuroImage 61:1277–1286. doi: 10.1016/j.neuroimage.2012.03.068 PubMedCrossRefGoogle Scholar
  79. Meyer-Lindenberg A, Hariri AR, Munoz KE, Mervis CB, Mattay VS, Morris CA, Berman KF (2005) Neural correlates of genetically abnormal social cognition in Williams syndrome. Nat Neurosci 8:991–93. doi: 10.1038/nn1494 PubMedCrossRefGoogle Scholar
  80. Mitchell JP, Mason MF, Macrae CN, Banaji MR (2006) Thinking about others: the neural substrates of social cognition. In: Cacioppo JT, Visser PS, Pickett CL (eds) Social Neuroscience: people thinking about thinking people. MIT Press, Cambridge, pp 63–82Google Scholar
  81. Moberg CA, Curtin JJ (2009) Alcohol selectively reduces anxiety but not fear: startle response during unpredictable vs. predictable threat. J Abnorm Psychol 118:335–347. doi: 10.1037/a0015636 PubMedCrossRefGoogle Scholar
  82. Morris AB, Albery IP (2001) Alcohol consumption and HIV risk behaviours: integrating the theories of alcohol myopia and outcome expectancies. Addict Res Theory 9:73–86. doi: 10.3109/16066350109141773 CrossRefGoogle Scholar
  83. Murphy FC, Nimmo-Smith I, Lawrence AD (2003) Functional neuroanatomy of emotions: a meta-analysis. Cogn Affect Behav Neurosci 3:207–233. doi: 10.3758/CABN.3.3.207 Google Scholar
  84. Murray EA, Izquierdo AD (2007) Orbitofrontal cortex and amygdala contributions to affect and action in primates. Ann NY Acad Sci 1121:273–296. doi: 10.1196/annals.1401.021 PubMedCrossRefGoogle Scholar
  85. National Institute on Alcohol Abuse and Alcoholism (NIAAA; 2005a) Helping patients with alcohol problems: a clinician’s guide. NIH Pub No. 05–3769. Bethesda, MDGoogle Scholar
  86. National Institute on Alcohol Abuse and Alcoholism (NIAAA; (2005b) Recommended council guidelines on ethyl alcohol administration in human experimentation. National Advisory Council on Alcohol Abuse and Alcoholism, BethesdaGoogle Scholar
  87. Nie Z, Schweitzer P, Roberts AJ, Madamba SG, Moore SD, Siggins GR (2004) Ethanol augments GABAergic transmission in the central amygdala via CRF1 receptors. Science 303:1512–1514PubMedCrossRefGoogle Scholar
  88. Nomura M, Ohira H, Haneda K, Iidaka T, Sadato N, Okada T, Yonekura Y (2004) Functional association of the amygdale and ventral prefrontal cortex during cognitive evaluation of facial expressions primed by masked angry faces: An event-related fMRI study. NeuroImage 21:352–363. doi: 10.1016/j.neuroimage.2003.09.021 PubMedCrossRefGoogle Scholar
  89. Nutt DJ, Peters TJ (1994) Alcohol: the drug. Br Med Bull 50:5–17PubMedGoogle Scholar
  90. Ochsner KN, Bunge SA, Gross JJ, Gabrieli JD (2002) Rethinking feelings: an FMRI study of the cognitive regulation of emotion. J Cogn Neurosci 14:1215–29. doi: 10.1162/089892902760807212 PubMedCrossRefGoogle Scholar
  91. O’Daly OG, Trick L, Scaife J, Marshall J, Ball D, Phillips ML, Williams SC, Stephens DN, Duka T (2012) Withdrawal-associated increases and decreases in functional neural connectivity associated with altered emotional regulation in alcoholism. Neuropsychopharmacol 37:2267–2276. doi: 10.1038/npp.2012.77 CrossRefGoogle Scholar
  92. Ochsner KN, Ray RD, Cooper JC, Robertson ER, Chopra S, Gabrieli JD, Gross JJ (2004) For better or for worse: neural systems supporting the cognitive down- and up- regulation of negative emotion. NeuroImage 23:483–99. doi: 10.1016/j.neuroimage.2004.06.030 PubMedCrossRefGoogle Scholar
  93. Ohira H, Nomura M, Ichikawa N, Isowa T, Iidaka T, Sato A, Fukuyama S, Nakajima T, Yamada J (2006) Association of neural and physiological responses during voluntary emotion suppression. NeuroImage 29:721–733. doi: 10.1016/j.neuroimage.2005.08.047 PubMedCrossRefGoogle Scholar
  94. Parent MB, Krebs-Kraft DL, Ryan JP, Wilson JS, Harenski C, Hamann S (2011) Glucose administration enhances fMRI brain activation and connectivity related to episodic memory encoding for neutral and emotional stimuli. Neuropsychologia 49:1052–1066. doi: 10.1016/j.neuropsychologia.2011.02.013 PubMedCrossRefGoogle Scholar
  95. Parrott DJ, Zeichner A, Stephens D (2003) Effects of alcohol, personality, and provocation on the expression of anger in men: a facial coding analysis. Alcohol Clin Exp Res 27:937–945. doi: 10.1111/j.1530-0277.2003.tb04418.x PubMedCrossRefGoogle Scholar
  96. Paulus MP, Feinstein JS, Castillo G, Simmons AN, Stein MB (2005) Dose dependent decrease of activation in bilateral amygdala and insula by lorazepam during emotion processing. Arch Gen Psychiat 62:282–288. doi: 10.1001/archpsyc.62.3.282 PubMedCrossRefGoogle Scholar
  97. Phan KL, Angstadt M, Golden J, Onyewuenui I, Povpovska A, de Wit H (2008) Cannabinoid modulation of amygdala reactivity to social signals of threat in humans. J Neurosci 28:2313–2319. doi: 10.1523/JNEUROSCI.5603-07.2008 PubMedCrossRefGoogle Scholar
  98. Phan KL, Fitzgerald DA, Nathan PJ, Moore GJ, Uhde TW, Tancer ME (2005) Neural substrates for voluntary suppression of negative affect: a functional magnetic resonance imaging study. Biol Psychiat 57:210–9. doi: 10.1016/j.biopsych.2004.10.030 PubMedCrossRefGoogle Scholar
  99. Phan KL, Wager T, Taylor SF, Liberzon I (2002) Functional neuroanatomy of emotion: a meta-analysis of emotion activation studies in PET and fMRI. NeuroImage 16:331–348. doi: 10.1006/nimg.2002.1087 PubMedCrossRefGoogle Scholar
  100. Phelps EA (2004) Human emotion and memory: interactions of the amygdala and hippocampal complex. Curr Opin Neurol 14:198–202. doi: 10.1016/j.conb.2004.03.015 CrossRefGoogle Scholar
  101. Pichon S, de Gelder B, Grezes J (2009) Two different faces of threat. Comparing the neural systems for recognizing fear and anger in dynamic body expressions Neuroimage 47:1873–1883. doi: 10.1016/j.neuroimage.2009.03.084 Google Scholar
  102. Pitel AL, Chanraud S, Müller-Oehring EM, Pfefferbaum A, Sullivan EV (2012) Modulation of limbic–cerebellar functional connectivity enables alcoholics to recognize who is who. Brain Struct Funct 1–13. doi:  10.1007/s00429-012-0421-6
  103. Porrino JL, Crane AM, Goldman-Rakic PS (1981) Direct and indirect pathways from the amygdala and to the frontal lobe in rhesus monkeys. J Comp Neurol 198:121–136. doi: 10.1002/cne.901980111 Google Scholar
  104. Prater KE, Hosanagar A, Klumpp H, Angstadt M, Phan KL (2012) Aberrant amygdala–frontal cortex connectivity during perception of fearful faces and at rest in generalized social anxiety disorder. Depress Anxiety 00:1–8. doi: 10.1002/da.22014 Google Scholar
  105. Price JL (2003) Comparative aspects of amygdala connectivity. Ann N Y Acad Sci 985:50–58. doi: 10.1111/j.1749-6632.2003.tb07070.x PubMedCrossRefGoogle Scholar
  106. Rabinak CA, Angstadt M, Welsh RC, Kenndy AE, Lyubkin M, Martis B, Phan KL (2011) Altered amygdala resting-state functional connectivity in post-traumatic stress disorder. Frontiers Psychiat 2:62. doi: 10.3389%2Ffpsyt.2011.00062 Google Scholar
  107. Rauch SL, Shin LM, Phelps EA (2006) Neurocircuitry models of posttraumatic stress disorder and extinction: human neuroimaging research—past, present, and future. Biol Psychiat 60:376–382. doi: 10.1016/j.biopsych.2006.06.004 PubMedCrossRefGoogle Scholar
  108. Ray JP, Price JL (1993) The organization of projections from the mediodorsal nucleus of the thalamus to orbital and medial prefrontal cortex in macaque monkeys. J Comp Neurol 337:1–31. doi: 10.1002/cne.903370102 PubMedCrossRefGoogle Scholar
  109. Roberto M, Madamba SG, Stouffer DG, Parsons LH, Siggins GR (2004) Increased GABA release in the central amygdala of ethanol-dependent rats. J Neurosci 24:10159–10166. doi: 10.1523/JNEUROSCI.3004-04.2004 PubMedCrossRefGoogle Scholar
  110. Rogers BP, Parks MH, Nickel MK, Katwal SB, Martin PR (2012) Reduced fronto–cerebellar functional connectivity in chronic alcoholic patients. Alcohol Clin Exp Res 36:294–301. doi: 10.1111/j.1530-0277.2011.01614.x PubMedCrossRefGoogle Scholar
  111. Rueger SY, McNamara PJ, King AC (2009) Expanding the utility of the Biphasic Alcohol Effects Scale (BAES) and initial psychometric support for the Brief-BAES (B-BAES). Alcohol Clin Exp Res 33:916–924. doi: 10.1111/j.1530-0277.2009.00914.x PubMedCrossRefGoogle Scholar
  112. SAMHSA (2005) National survey on drug use and health. Office of Applied Studies, BethesdaGoogle Scholar
  113. Saddoris MP, Gallagher M, Schoenbaum G (2005) Rapid associative encoding in basolateral amygdala depends on connections with orbitofrontal cortex. Neuron 46:321–331. doi: 10.1016/j.neuron.2005.02.018 PubMedCrossRefGoogle Scholar
  114. Sayette MA (1993) An appraisal-disruption model of alcohol's effectiveness on stress responses in social drinkers. Psychol Bull 114:459–476. doi: 10.1037/0033-2909.114.3.459 PubMedCrossRefGoogle Scholar
  115. Sayette MA, Martin CS, Perrott MA, Wertz JM, Hufford MR (2001) A test of the appraisal-disruption model of alcohol and stress. J Stud Alcohol 62:247–256PubMedGoogle Scholar
  116. Sayette MA, Smith DW, Breiner MJ, Wilson GT (1992) The effect of alcohol on emotional response to a social stressor. J Stud Alcohol 53:541–545PubMedGoogle Scholar
  117. Schaefer SM, Jackson DC, Davidson RJ, Aguirre GK, Kimberg DY, Thompson-Schill SL (2002) Modulation of amygdalar activity by the conscious regulation of negative emotion. J Cognitive Neurosci 14:913–921. doi: 10.1162/089892902760191135 Google Scholar
  118. Sobell LC, Sobell MB (1995) Alcohol timeline follow-back users’ manual. Addiction Research Foundation, TorontoGoogle Scholar
  119. Spielberger CD, Gorsuch RL, Luschene R (1970) Test manual for the state–trait anxiety inventory. Consulting Psychologists Press, Palo AltoGoogle Scholar
  120. Sripada CS, Angstadt M, McNamara P, King AC, Phan KL (2011) Effects of alcohol on brain responses to social signals of threat in humans. NeuroImage 55:371–380. doi: 10.1016/j.neuroimage.2010.11.062 PubMedCrossRefGoogle Scholar
  121. Steele CM, Josephs RA (1990) Alcohol myopia: its prized and dangerous effects. Amer Psychol 45:921–933. doi: 10.1037/0003-066X.45.8.921 CrossRefGoogle Scholar
  122. Stein JL, Wiedholz LM, Bassett DS, Weinberger DR, Zink CF, Mattay VS, Meyer-Lindenberg A (2007) A validated network of effective amygdala connectivity. NeuroImage 36:736–745. doi: 10.1016/j.neuroimage.2007.03.022 PubMedCrossRefGoogle Scholar
  123. Stenger VA, Boada FE, Noll DC (2000) Three–dimensional tailored RF pulses for the reduction of susceptibility artifacts in T(*)(2)–weighted functional MRI. Mag Reson Med 44:525–531. doi: 10.1002/1522-2594(200010)44:4<525::AID-MRM5>3.0.CO;2-L CrossRefGoogle Scholar
  124. Sutker PB, Tabakoff B, Goist KC Jr, Randall CL (1983) Acute alcohol intoxication, mood states and alcohol metabolism in women and men. Pharmacol Biochem Be 18(Suppl 1):349–354. doi: 10.1016/0091-3057(83)90198-3 CrossRefGoogle Scholar
  125. Talalaenko AN, Abramets IA, Stakhovskii Yu V, Shekhovtsov AA, Chernikov AV, Shevchenko SL (1994) The role of dopaminergic mechanisms on the brain in various models of anxious states. Neurosci Behav Physiol 24:284–288. doi: 10.1007/BF02362037 PubMedCrossRefGoogle Scholar
  126. Tebartz van Elst L, Hesslinger B, Thiel T, Geiger E, Haegele K, Lemieux L, Lieb K, Bohus M, Henning J, Ebert D (2003) Frontolimbic brain abnormalities in patients with borderline personality disorder: a volumetric magnetic resonance imaging study. Biol Psychiat 54:163–171. doi: 10.1016/S0006-3223(02)01743-2 PubMedCrossRefGoogle Scholar
  127. Urry HL, van Reekum CM, Johnstone T, Kalin NH, Thurow ME, Schaefer HS et al (2006) Amygdala and ventromedial prefrontal cortex are inversely coupled during regulation of negative affect and predict the diurnal pattern of cortisol secretion among older adults. J Neurosci 26:4415–25. doi: 10.1523/JNEUROSCI.3215-05.2006 PubMedCrossRefGoogle Scholar
  128. Weiner JL, Valenzuela CF (2006) Ethanol modulation of GABAergic transmission: the view from the slice. Pharmacol therapeut 111:533–554. doi: 10.1016/j.pharmthera.2005.11.002 CrossRefGoogle Scholar
  129. Whalen PJ (1998) Fear, vigilance, and ambiguity: initial neuroimaging studies of the human amygdala. Curr Dir Psychol Sci 7:117–188CrossRefGoogle Scholar
  130. Whalen PJ, Shin LM, McInerney SC, Fischer H, Wright CI, Rauch SL (2001) A functional MRI study of human amygdala responses to facial expressions of fear versus anger. Emotion 1:70–83. doi: 10.1037/1528-3542.1.1.70 PubMedCrossRefGoogle Scholar
  131. de Wit H, Crean J, Richards JB (2000) Effects of d-amphetamine and ethanol on a measure of behavioral inhibition in humans. Behav Neurosci 114:830–837. doi: 10.1037/0735-7044.114.4.830 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg (outside the USA) 2013

Authors and Affiliations

  • Stephanie M. Gorka
    • 1
  • Daniel A. Fitzgerald
    • 2
  • Andrea C. King
    • 3
  • K. Luan Phan
    • 2
    • 4
    Email author
  1. 1.Department of PsychologyUniversity of Illinois–ChicagoChicagoUSA
  2. 2.Department of PsychiatryUniversity of Illinois–ChicagoChicagoUSA
  3. 3.Department of Psychiatry and Behavioral NeurosciencesUniversity of ChicagoChicagoUSA
  4. 4.Jesse Brown VA Medical CenterMental Health Service LineChicagoUSA

Personalised recommendations