title: A combined spectroscopic and functional MRI investigation of the dorsal anterior cingulate region in opiate addiction.
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 ((1)H-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.
authors.affiliation: ORYGEN Research Centre, Melbourne, VIC, Australia. murat@unimelb.edu.au
authors.forename: M
authors.initials: M
authors.lastname: Yücel
authors.forename: D I
authors.initials: DI
authors.lastname: Lubman
authors.forename: B J
authors.initials: BJ
authors.lastname: Harrison
authors.forename: A
authors.initials: A
authors.lastname: Fornito
authors.forename: N B
authors.initials: NB
authors.lastname: Allen
authors.forename: R M
authors.initials: RM
authors.lastname: Wellard
authors.forename: K
authors.initials: K
authors.lastname: Roffel
authors.forename: K
authors.initials: K
authors.lastname: Clarke
authors.forename: S J
authors.initials: SJ
authors.lastname: Wood
authors.forename: S D
authors.initials: SD
authors.lastname: Forman
authors.forename: C
authors.initials: C
authors.lastname: Pantelis
mesh_terms: D000222:Adaptation, Physiological; D000328:Adult; D000704:Analysis of Variance; D001143:Arousal / Q000502:physiology*; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D001931:Brain Mapping; D016022:Case-Control Studies; D002531:Cerebellum / Q000502:physiology / Q000503:physiopathology; D005260:Female; D005625:Frontal Lobe / Q000502:physiology / Q000503:physiopathology; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006179:Gyrus Cinguli / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D016555:Matched-Pair Analysis; D009293:Opioid-Related Disorders / Q000378:metabolism / Q000503:physiopathology*; D010296:Parietal Lobe / Q000502:physiology / Q000503:physiopathology; D011597:Psychomotor Performance / Q000502:physiology; D013997:Time Factors
chemical_list: D005973:Glutamine; D001224:Aspartic Acid; D018698:Glutamic Acid; C000179:N-acetylaspartate