, Volume 188, Issue 3, pp 364–373 | Cite as

Differences in orbitofrontal activation during decision-making between methadone-maintained opiate users, heroin users and healthy volunteers

  • Karen D. ErscheEmail author
  • Paul C. Fletcher
  • Jonathan P. Roiser
  • Tim D. Fryer
  • Mervyn London
  • Trevor W. Robbins
  • Barbara J. Sahakian
Original Investigation



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.


We sought to explore this finding from a neural perspective by performing a post hoc analysis of data from a previous \( H^{{15}}_{2} O \) 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.


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.


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.


Heroin Methadone Orbitofrontal Anterior cingulate Decision making Punishment Feedback Opiates Neuroimaging 



This work was funded by a Wellcome Trust Programme Grant to Professors TWR, BJ Everitt, BJ S and Dr AC Roberts and carried out within the University of Cambridge Behavioural and Clinical Neuroscience Institute (supported by a joint award from the Medical Research Council and the Wellcome Trust). KDE is a recipient of the Betty Behrens Research Fellowship at Clare Hall, University of Cambridge, and was supported for research work on substance abuse by Fund for Addenbrooke’s and the Grindley Fund. PCF was supported by the Wellcome Trust, and JPR was supported by the Medical Research Council. The authors are grateful to all study participants and the key workers Nick Schiller and Marion Martin for help with the recruitment, Dr. Robert Rogers for providing the Risk Task and Dr. Andrew Blackwell for graphical assistance. The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Karen D. Ersche
    • 1
    • 2
    Email author
  • Paul C. Fletcher
    • 1
    • 2
  • Jonathan P. Roiser
    • 1
    • 2
  • Tim D. Fryer
    • 3
  • Mervyn London
    • 4
  • Trevor W. Robbins
    • 2
    • 5
  • Barbara J. Sahakian
    • 1
    • 2
  1. 1.Department of Psychiatry, School of Clinical MedicineUniversity of CambridgeCambridgeUK
  2. 2.Behavioural and Clinical Neuroscience InstituteUniversity of CambridgeCambridgeUK
  3. 3.Wolfson Brain Imaging Centre, Addenbrooke’s HospitalUniversity of CambridgeCambridgeUK
  4. 4.Cambridge Drug and Alcohol ServiceBrookfields HospitalCambridgeUK
  5. 5.Department of Experimental PsychologyUniversity of CambridgeCambridgeUK

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