Aversive Counterconditioning Attenuates Reward Signaling in the Ventral Striatum

Abstract

Appetitive conditioning refers to the process of learning cue-reward associations and is mediated by the mesocorticolimbic system. Appetitive conditioned responses are difficult to extinguish, especially for highly salient reward such as food and drugs. We investigate whether aversive counterconditioning can alter reward reinstatement in the ventral striatum in healthy volunteers using functional magnetic resonance imaging (fMRI). In the initial conditioning phase, two different stimuli were reinforced with a monetary reward. In the subsequent counterconditioning phase, one of these stimuli was paired with an aversive shock to the wrist. In the following extinction phase, none of the stimuli were reinforced. In the final reinstatement phase, reward was reinstated by informing the participants that the monetary gain could be doubled. Our fMRI data revealed that reward signaling in the ventral striatum and ventral tegmental area following reinstatement was smaller for the stimulus that was counterconditioned with an electrical shock, compared to the non-counterconditioned stimulus. A functional connectivity analysis showed that aversive counterconditioning strengthened striatal connectivity with the hippocampus and insula. These results suggest that reward signaling in the ventral striatum can be attenuated through aversive counterconditioning, possibly by concurrent retrieval of the aversive association through enhanced connectivity with hippocampus and insula.

Keywords: counterconditioning; fMRI; reward reinstatement; ventral striatum.

FIGURE 1

(A) Trial sequence for conditioning phase. 50% of the CS+ trials were reinforced with a monetary gain. Each stimulus is presented 20 times. (B) Trial sequence for counterconditioning phase. The CS+_cc stimuli are reinforced with an electrical shock, the other stimuli are not reinforced. Each stimulus is presented three times. (C) Trial sequence for extinction phase. None of the stimuli is reinforced. Each stimulus is presented 20 times. (D) Reward is reinstated by showing this text. (E) The trial sequence for the reinstatement phase is similar to the trial sequence of the extinction phase. Each stimulus is presented 20 times.

FIGURE 2

The neural response to counterconditioned versus non-counterconditioned CS+. The figures on the left (A) show the neural responses after reinstatement to the counterconditioned versus the non-counterconditioned CS+stimuli in the ventral striatum. The bar graphs on the right (B) are a visual presentation of the response to the counterconditioned CS+ (CS+_cc; black), non-counterconditioned CS+ (CS+_nc; gray) and CS- (white) at the peak voxel (MNI: 12 10 -6, z = 2.91). Compared to the conditioning phase, ventral striatal BOLD response during reinstatement is significantly decreased for the counterconditioned CS+, but not for the other stimuli. During reinstatement, the ventral striatal BOLD response for the non-counter CS is significantly higher compared to the BOLD response for the counterconditioned stimulus. The figures are displayed at p < 0.001 uncorrected for visualization purpose. ^∗ = whole brain significant stimulus type (CS+_cc versus CS+_nc) by phase (conditioning versus reinstatement) interaction effect.

FIGURE 3

Functional connectivity of the ventral striatum. The figure shows significant differences in functional connectivity for the counterconditioned versus non-counterconditioned CS+ following reinstatement. Counterconditioning strengthened the functional connectivity of the ventral striatum seed region (left) with the left insula (A) and left hippocampus (B). The figures are displayed at p < 0.001 uncorrected for visualization purpose. The graph (C) is a visual representation of the functional connectivity changes with the ventral striatum in response to counterconditioned and non-counterconditioned CS+, in the insula and hippocampus. ^∗ = whole brain significant main effect of stimulus type (CS+_cc versus CS+_nc) on ventral striatal connectivity following reward reinstatement.