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

Abstract

RationaleIndividuals 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.

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

MethodsFourteen 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 ~18mg% in 200s 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.

ResultsCS− 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.

ConclusionsNovel 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.

KeywordsAlcohol–Alcoholism–Imaging–Brain–Frontal–Classical conditioning