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

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.