Temporal difference modeling of the blood-oxygen level dependent response during aversive conditioning in humans: Effects of dopaminergic modulation

Background: The prediction error (PE) hypothesized by the temporal difference model has been shown to correlate with the phasic activity of dopamine neurons during reward learning and the blood-oxygen level dependent (BOLD) response during reward and aversive conditioning tasks. We hypothesized that dopamine would modulate the PE related signal in aversive conditioning and that haloperidol would reduce PE related activity, while an acute dose of amphetamine would increase PE related activity in the ventral striatum. Methods: Healthy participants took an acute dose of amphetamine, haloperidol, or placebo. We used functional magnetic resonance imaging (fMRI) to measure the BOLD signal while they carried out an aversive conditioning task, using cutaneous electrical stimulation as the unconditioned stimulus (US) and yellow and blue circles as conditioned stimulus (CS+ and CS-, respectively). Results: Prediction error related BOLD activity was seen only in the ventral striatum in the placebo subjects. The subjects given amphetamine showed a wider network of PE related BOLD activity, including the ventral striatum, globus pallidus, putamen, insula, anterior cingulate, and substantia nigra/ventral tegmental area. Haloperidol subjects did not show PE related activity in any of these regions. Conclusions: Our results provide the first demonstration that the modulation of dopamine transmission affects both the physiological correlates and PE related BOLD activity during aversive learning.