, Volume 235, Issue 9, pp 2725–2737 | Cite as

Pairing neutral cues with alcohol intoxication: new findings in executive and attention networks

  • Brandon G. OberlinEmail author
  • Mario Dzemidzic
  • William J.A. EilerII
  • Claire R. Carron
  • Christina M. Soeurt
  • Martin H. Plawecki
  • Nicholas J. Grahame
  • Sean J. O’Connor
  • David A. Kareken
Original Investigation



Alcohol-associated stimuli capture attention, yet drinkers differ in the precise stimuli that become paired with intoxication.


Extending our prior work to examine the influence of alcoholism risk factors, we paired abstract visual stimuli with intravenous alcohol delivered covertly and examined brain responses to these Pavlovian-conditioned stimuli in fMRI when subjects were not intoxicated.


Sixty healthy drinkers performed task-irrelevant alcohol conditioning that presented geometric shapes as conditioned stimuli. Shapes were paired with a rapidly rising alcohol limb (conditioned stimulus; CS+) using intravenous alcohol infusion targeting a final peak breath alcohol concentration of 0.045 g/dL or saline (CS−) infusion at matched rates. On day 2, subjects performed monetary delay discounting outside the scanner to assess delay tolerance and then underwent event-related fMRI while performing the same task with CS+, CS−, and an irrelevant symbol.


CS+ elicited stronger activation than CS− in frontoparietal executive/attention and orbitofrontal reward-associated networks. Risk factors including family history, recent drinking, sex, and age of drinking onset did not relate to the [CS+ > CS−] activation. Delay-tolerant choice and [CS+ > CS−] activation in right inferior parietal cortex were positively related.


Networks governing executive attention and reward showed enhanced responses to stimuli experimentally paired with intoxication, with the right parietal cortex implicated in both alcohol cue pairing and intertemporal choice. While different from our previous study results in 14 men, we believe this paradigm in a large sample of male and female drinkers offers novel insights into Pavlovian processes less affected by idiosyncratic drug associations.


Classical conditioning Cue reactivity Associative conditioning Laboratory task Ethanol BA 40 Intertemporal choice Alcoholism Addiction 



The authors acknowledge the excellent technical assistance of Dr. Yu-Chien Wu, Dr. Sourajit Mustafi, Michele Dragoo, Traci Day, and Robert Bryant Jr. (MRI facility); Tetlu Myint and Caron Peper (Neuropsychology Research); and prior analytic contributions by Matthew Yung, Marta Karas, and Jourdan Carroll. The IARC’s Computer-assisted Alcohol Infusion System ( managed the infusions employed in this research.

Funding information

This study is supported by grants from the National Institute on Alcohol Abuse and Alcoholism (Indiana Alcohol Research Center, P60AA07611 to DAK; R00AA023296 to BGO). Additional support was provided by the Indiana Clinical and Translational Sciences Institute Clinical Research Center (UL1TR001108), National Institutes of Health, National Center for Advancing Translational Sciences, and Clinical and Translational Sciences.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

213_2018_4968_Fig5_ESM.png (106 kb)
Fig. S1

Activation by cluster and scan. Mean values from the functional clusters in Table 3 for the [CS+ > CS−] contrast are illustrated here by scan, and ordered as in Table 3 from top left to bottom right. OFC, orbitofrontal cortex; ACC, anterior cingulate cortex; BA, Brodmann Area; MFG, middle frontal gyrus; AngG, angular gyrus; SFG, superior frontal gyrus; SMG, supramarginal gyrus. (PNG 105 kb)

213_2018_4968_MOESM1_ESM.tif (1.5 mb)
High Resolution image (TIF 1.45 MB)
213_2018_4968_MOESM2_ESM.docx (14 kb)
Table S1 (DOCX 13.7 kb)
213_2018_4968_MOESM3_ESM.docx (16 kb)
Table S2 (DOCX 16.2 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Brandon G. Oberlin
    • 1
    • 2
    • 3
    • 4
    Email author
  • Mario Dzemidzic
    • 2
    • 5
  • William J.A. EilerII
    • 2
  • Claire R. Carron
    • 2
  • Christina M. Soeurt
    • 2
  • Martin H. Plawecki
    • 1
  • Nicholas J. Grahame
    • 4
  • Sean J. O’Connor
    • 1
    • 6
  • David A. Kareken
    • 1
    • 2
    • 3
    • 5
  1. 1.Department of Psychiatry, School of MedicineIndiana UniversityIndianapolisUSA
  2. 2.Department of Neurology, School of MedicineIndiana UniversityIndianapolisUSA
  3. 3.Stark Neurosciences Institute, School of MedicineIndiana UniversityIndianapolisUSA
  4. 4.Department of PsychologyIndiana University–Purdue University IndianapolisIndianapolisUSA
  5. 5.Department of Radiology and Imaging Sciences, School of MedicineIndiana UniversityIndianapolisUSA
  6. 6.Roudebush Veteran’s Administration Medical CenterIndianapolisUSA

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