Pairing neutral cues with alcohol intoxication: new findings in executive and attention networks
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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.
KeywordsClassical 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 (firstname.lastname@example.org) managed the infusions employed in this research.
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.
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