In apparent contrast to the above findings suggesting increased striatal-PFC rsFC strength, a widespread reduction in connectivity between NAc and various subcortical (hippocampus and amygdala) and cortical (parietal, cingulate, prefrontal) regions in prescription opioid addicts (n=10) has been described (Upadhyay et al., 2010). Individuals in that study were current users, thus results may in part reflect effects of recent opiate use. Nonetheless, a similar pattern of MCL circuit reductions was reported by Gu and colleagues (2010) who conducted a rsFC assessments in a relatively large population (n=39) of active cocaine-users and a matched, non-using control group. They observed a general decrease in rsFC between most regions within the MCL reward pathway and interconnected brain areas (with the notable exception of the NAc, whose connectivity remained unchanged between groups) (Fig 1A). Such widespread reductions in the connectivity of multiple MCL system components may reflect putative difficulty in appropriately engaging reward, motivational, and emotional circuitry, which is consistent with perspectives suggesting that the transition from drug-use to addiction is driven by reduced functioning of reward systems, with concurrently increased activation of ‘anti-reward’
