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fMRI of the brain’s response to stimuli experimentally paired with alcohol intoxication

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Abstract

Rationale

Individuals learn associations between alcohol’s sensory properties and intoxication, with such conditioned stimuli (CS) becoming involved in craving and relapse. However, these CS also carry idiosyncratic associations.

Objectives

This study aimed to test brain responses to novel CS conditioned with alcohol intoxication.

Methods

Fourteen heavy drinkers (age 24.9 ± 3.2) performed a reaction time task with embedded novel geometric CS and were told only that the task was to measure alcohol’s effect on speed. Rapid intravenous alcohol infusion (the unconditioned stimulus; UCS) began with the appearance of a CS+, using pharmacokinetic modeling to increment breath alcohol by ~18 mg% in 200 s per each of six CS–UCS pairings. Placebo–saline infusion with CS− used the same infusion parameters in same-day randomized/counterbalanced sessions. The next morning subjects, connected to inactive intravenous pumps, underwent functional magnetic resonance imaging (fMRI) of the same task with mixed brief presentations of CS+, CS−, and irrelevant CS and were told that alcohol could be infused at any time during imaging.

Results

CS− responses were significantly greater than those of CS+ in medial frontal cortex. Notably, CS+ responses were negative, suggesting reduced neural activity. Negative activity was most pronounced in early scans, extinguishing with time. As subjects were told that alcohol could be administered in fMRI, a CS+ without alcohol is similar to a negative prediction error, with associated reduced frontal activity during withheld reward.

Conclusions

Novel stimuli relatively free of demand characteristics can be classically conditioned to intermittent brain exposure of even low alcohol concentrations, permitting imaging studies of conditioned alcohol expectancies.

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Acknowledgments

This study was supported by R21 AA018020 (DAK), R01 AA017661 (DAK), the Indiana Alcohol Research Center P60 AA007611, T32 AA007462, and the Indiana University Clinical Research Center (RR 025761). We gratefully acknowledge Kyle Windisch (Department of Psychiatry) for paradigm programming, Michele Beal and Courtney Robbins for assistance with imaging (Department of Radiology), and Kieren Mather, M.D. (Department of Medicine) for assistance with medical supervision.

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Authors and Affiliations

  1. Department of Neurology, Indiana University School of Medicine, 541 Clinical Drive (CL 285), Indianapolis, IN, 46202, USA

    David A. Kareken, Mario Dzemidzic, Melissa J. Walker & Cari A. Lehigh

  2. Department of Radiology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA

    David A. Kareken & Mario Dzemidzic

  3. Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, 46202, USA

    David A. Kareken & Sean J. O’Connor

  4. Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, 46202, USA

    David A. Kareken & Melissa J. Walker

  5. Department of Psychology, Indiana University-Purdue University Indianapolis (IUPUI), Indianapolis, IN, 46202, USA

    Nicholas Grahame

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  1. David A. Kareken
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Correspondence to David A. Kareken.

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Kareken, D.A., Grahame, N., Dzemidzic, M. et al. fMRI of the brain’s response to stimuli experimentally paired with alcohol intoxication. Psychopharmacology 220, 787–797 (2012). https://doi.org/10.1007/s00213-011-2526-7

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  • DOI: https://doi.org/10.1007/s00213-011-2526-7

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