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A combined spectroscopic and functional MRI investigation of the dorsal anterior cingulate region in opiate addiction

Molecular Psychiatry volume 12, pages 691–702 (2007)Cite this article

Abstract

Converging neuropsychological and functional neuroimaging evidence indicates that the dorsal anterior cingulate cortex (dACC) is dysfunctional in drug-addicted populations. Few studies, however, have investigated the biochemical and physiological properties of the dACC in such populations. We used proton magnetic resonance spectroscopy (1H-MRS) together with functional magnetic resonance imaging (fMRI) to probe dACC biochemistry and physiological activity during performance of a behavioural control task in 24 opiate-dependent individuals (maintained on a stable dose of methadone or buprenorphine at the time of study) and 24 age, gender, intelligence and performance-matched healthy subjects. While both groups activated the dACC to comparable levels, the opiate-using group displayed relatively increased task-related activation of frontal, parietal and cerebellar regions, as well as reduced concentrations of dACC N-acetylaspartate and glutamate/glutamine. In addition, the opiate-using group failed to show the expected correlations between dACC activation and behavioural measures of cognitive control. These findings suggest that the dACC is biochemically and physiologically abnormal in long-term opiate-dependent individuals. Furthermore, opiate addicts required increased, perhaps compensatory, involvement of the fronto-parietal and cerebellar behavioural regulation network to achieve normal levels of task performance/behavioural control. These neurobiological findings may partly underpin key addiction-related phenomena, such as poor inhibitory control of drug-related behaviour in the face of adverse consequences, and may be of relevance to the design of future treatment studies.

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Acknowledgements

This research was supported by the National Health and Medical Research Council (NHMRC) of Australia (I.D. 236175), a Pfizer Neuroscience Research Grant, the Colonial Foundation, and the Ian Potter Foundation. Dr Yücel is supported by a NHMRC Program Grant (I.D. 350241). Dr Harrison is supported by a NHMRC Training Award (I.D. 400420). Dr Fornito is supported by an Australian Postgraduate Award, J.N. Peters Fellowship, and an NHMRC Training Award (I.D. 454797). Dr Wood is supported by an NHMRC Clinical Career Development Award and a NARSAD Young Investigator Award. Dr Forman is supported by the US Department of Veterans’ Affairs VISN4 MIRECC. Neuroimaging analysis was facilitated by the Neuropsychiatry Imaging Laboratory managed by Ms Bridget Soulsby at the Melbourne Neuropsychiatry Centre and supported by Neurosciences Victoria. The authors would also like to thank Trudi MacKenzie and Antonietta Scaffidi for their efforts in patient recruitment and assessment, Dr Steven Grant for his advice on study design, The Mental Health Research Institute for research and administrative support and NIDA for providing a travel scholarship to present these findings at the College on Problems of Drug Dependence (CPDD) conference, San Juan, Puerto Rico.

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Authors and Affiliations

  1. ORYGEN Research Centre, Melbourne, VIC, Australia

    M Yücel, D I Lubman, N B Allen, K Roffel & K Clarke

  2. Melbourne Neuropsychiatry Centre, Melbourne, VIC, Australia

    M Yücel, B J Harrison, A Fornito, S J Wood & C Pantelis

  3. Department of Psychiatry, The University of Melbourne, Melbourne, VIC, Australia

    M Yücel, D I Lubman, B J Harrison, S J Wood & C Pantelis

  4. Institut d'Alta Tecnologia-PRBB, CRC Corporació Sanitària, Barcelona, Spain

    B J Harrison

  5. Department of Psychology, The University of Melbourne, Melbourne, VIC, Australia

    A Fornito & N B Allen

  6. Brain Research Institute, Austin & Repatriation Medical Centre, Melbourne, VIC, Australia

    R M Wellard & S J Wood

  7. School of Physical and Chemical Sciences, Queensland University of Technology, Brisbane, QLD, Australia

    R M Wellard

  8. US Department of Veterans Affairs Medical Center, Pittsburgh, PA, USA

    S D Forman

  9. Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA

    S D Forman

  10. Howard Florey Institute, The University of Melbourne, Melbourne, VIC, Australia

    C Pantelis

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  1. M Yücel
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Yücel, M., Lubman, D., Harrison, B. et al. A combined spectroscopic and functional MRI investigation of the dorsal anterior cingulate region in opiate addiction. Mol Psychiatry 12, 691–702 (2007). https://doi.org/10.1038/sj.mp.4001955

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