title: Temporal difference modeling of the blood-oxygen level dependent response during aversive conditioning in humans: effects of dopaminergic modulation.
abstract: 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.
authors.affiliation: Schizophrenia Program and PET Centre, Centre for Addiction and Mental Health, Toronto, Canada.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Menon
authors.forename: Jimmy
authors.initials: J
authors.lastname: Jensen
authors.forename: Irina
authors.initials: I
authors.lastname: Vitcu
authors.forename: Ariel
authors.initials: A
authors.lastname: Graff-Guerrero
authors.forename: Adrian
authors.initials: A
authors.lastname: Crawley
authors.forename: Mark A
authors.initials: MA
authors.lastname: Smith
authors.forename: Shitij
authors.initials: S
authors.lastname: Kapur
mesh_terms: D000293:Adolescent; D000328:Adult; D000661:Amphetamine / Q000494:pharmacology; D003214:Conditioning, Classical / Q000502:physiology*; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D005712:Galvanic Skin Response / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D010100:Oxygen / Q000097:blood*; D012054:Reinforcement, Psychology; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology
chemical_list: D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D000661:Amphetamine; D006220:Haloperidol; D010100:Oxygen; D004298:Dopamine