While clearly more work is needed to untangle the nature of rsFC changes in reward-related circuitry, a general pattern of perturbed connectivity across heterogeneous drug-using cohorts is consistent with a reward dysregulation hypothesis of drug addiction. That said, any effort to draw conclusions at this early stage must be tempered by consideration of the various methodological issues inherent to this literature. For example, relatively small samples sizes (Ma et al., 2010; Upadhyay et al., 2011; Wilcox et al., 2011) necessitate caution when interpreting findings. Additionally, the duration since last drug use and collection of imaging data has often not been adequately considered. Factors such as acute withdrawal (Gu et al., 2010; Ma et al., 2010; Tomasi et al., 2010; Wilcox et al 2011) or acute drug effects (Ma et al., 2010; Upadhyay et al., 2011) likely contribute significantly to variance both within and between rsFC studies, confounding interpretation of results. Finally, generalizing across different abused drugs is complicated by the potential for drug-specific effects on underlying neural circuitry. In sum, careful consideration of the above methodological factors will be necessary for future work to elucidate the precise nature of rsFC alterations in the reward-related neurocircuitry of drug addiction.
