A candidate mechanism in the development of substance dependence is the failure of top-down systems of self-regulation and effortful processing, particularly frontoparietal networks, to override subcortical

networks involved in habitual responses to reward cues, which are strengthened with accumulated exposure to drug cues and consumption (Koob 2006; Koob and Volkow 2010). Given the age range of our sample (ages 21–56), it is important to recognize that changes in FA and downstream changes in the function of neural networks may begin relatively early in the trajectory of problem drinking. Lower FA consistently Inhibitors,research,lifescience,medical showed significant correlations with greater BOLD activity in the thalamus, medial frontal gyrus, cingulate, and parahippocampal gyrus. One interpretation of this see more pattern is that individuals exhibit greater cue reactivity when bottom-up activity originating in the thalamus guides subsequent attentional orienting and salience attribution in the prefrontal cortex and limbic system. A great body of literature has demonstrated the role of prefrontal

cortex and cingulate Inhibitors,research,lifescience,medical Inhibitors,research,lifescience,medical in affective and reward-related decision making (Bechara et al. 1998; Bechara 2004; Rogers et al. 2004; Cohen et al. 2005). Because participants were not engaged in a decision-making task, it remains unknown how increased cue reactivity might affect these processes. However, one hypothesis for future study is that lower integrity of frontoparietal white matter networks mediates the relationship between increased cue reactivity and alcohol urges. It should be noted that white matter fiber tracts are largely bidirectional Inhibitors,research,lifescience,medical and that analyses did not investigate the temporal sequence of activation. Thus, an alternative mechanism that might operate instead of or in conjunction with weakened top-down control over bottom-up response is alteration of the signal communicated upward from subcortical to cortical regions as a result of changes in white matter integrity, affecting the processing of cue-eliciting Inhibitors,research,lifescience,medical stimuli. A recent meta-analysis of alcohol cue reactivity found that heavy drinkers reliably showed increased activation in the right caudate, cingulate cortex, thalamus,

and ventromedial prefrontal cortex relative to control cue conditions (Schacht et al. 2013). However, alcohol-elicited activation in these areas was not significantly greater in heavy-drinking groups compared to control Cediranib (AZD2171) groups, suggesting that the incentive salience of alcohol cues may be comparable across groups (Schacht et al. 2013). Areas that did differentiate AUD and control groups were the bilateral precuneus, left posterior cingulate, and left superior temporal gyrus. The findings of the current study converge with the meta-analytic findings, which demonstrated the importance of cue-elicited activity in posterior regions such as the precuneus and posterior cingulate in differentiating alcohol dependent from healthy individuals and varying as a function of severity.