title: Differences in orbitofrontal activation during decision-making between methadone-maintained opiate users, heroin users and healthy volunteers.
abstract: OBJECTIVE
  Previously, we reported that opiate users enrolled in methadone treatment made 'risky' choices on a decision-making task following a loss of points compared with heroin users and healthy volunteers. One possible explanation for this behaviour is that methadone users were less sensitive to punishment on immediately preceding unsuccessful trials.
  
  
  METHODS
  We sought to explore this finding from a neural perspective by performing a post hoc analysis of data from a previous [see text] positron emission tomography study. We restricted the analysis to the opiate groups and controls, assessing differences between opiate users on methadone and those on heroin.
  
  
  RESULTS
  We found significant over-activation in the lateral orbitofrontal cortex (OFC) in methadone users compared with both heroin users and controls concomitant with the greatest overall tendency to 'play risky'. Heroin users showed significant under-activation in this area compared with the other two groups whilst exhibiting the greatest overall tendency to 'play safe'. Correlational analysis revealed that abnormal task-related activation of the left OFC was associated with the dose of methadone in methadone users and with the duration of intravenous heroin use in heroin users. 'Playing safe' following a loss of points was also negatively correlated with the activation of pregenual anterior cingulate and insula cortex in controls, but not in opiate users.
  
  
  CONCLUSIONS
  Our findings suggest that the interplay between processes involved in integrating penalty information for the purpose of response selection may be altered in opiate users. This change was reflected differentially in task-related pattern of OFC activation depending on the opiate used.
authors.affiliation: Department of Psychiatry, School of Clinical Medicine, University of Cambridge, Brain Mapping Unit, Addenbrooke's Hospital, Cambridge, UK. ke220@cam.ac.uk
authors.forename: Karen D
authors.initials: KD
authors.lastname: Ersche
authors.forename: Paul C
authors.initials: PC
authors.lastname: Fletcher
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Roiser
authors.forename: Tim D
authors.initials: TD
authors.lastname: Fryer
authors.forename: Mervyn
authors.initials: M
authors.lastname: London
authors.forename: Trevor W
authors.initials: TW
authors.lastname: Robbins
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Sahakian
mesh_terms: D000328:Adult; D000367:Age Factors; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000627:therapeutic use; D000704:Analysis of Variance; D016739:Behavior, Addictive / Q000503:physiopathology / Q000523:psychology / Q000534:rehabilitation; D003657:Decision Making / Q000187:drug effects / Q000502:physiology*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D005625:Frontal Lobe / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology*; D006556:Heroin Dependence / Q000503:physiopathology* / Q000523:psychology; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008297:Male; D008691:Methadone / Q000008:administration & dosage* / Q000627:therapeutic use; D008875:Middle Aged; D009293:Opioid-Related Disorders / Q000503:physiopathology* / Q000523:psychology / Q000534:rehabilitation; D049268:Positron-Emission Tomography / Q000379:methods
chemical_list: D000701:Analgesics, Opioid; D008691:Methadone