2008a,b2008b; Fortin et al. 2012; Jones et al. 2013). Importantly, these tracts also project to regions known to respond during cue-elicited craving, including the supplementary motor area, medial frontal cortex, insula, and dorsal striatum (Claus et al. 2011; Schacht et al. 2013). In addition to posterior cortical regions, we

also found significant, inverse correlations between white matter integrity and BOLD response in frontal regions including the inferior, medial, and superior frontal gyri. Lateral Inhibitors,research,lifescience,medical frontal regions typically have been implicated in cognitive control and goal-directed behavior. Given that response to alcohol cues in the dorsolateral prefrontal cortex and medial frontal gyrus has been Inhibitors,research,lifescience,medical positively

associated with alcohol problem severity (Claus et al. 2011), our findings could be interpreted as providing further evidence of engagement of these regions in individuals with more extensive drinking histories. Inhibitors,research,lifescience,medical The negative correlation of BOLD activity in these regions with white matter integrity suggests the possibility that, although these regions may come online to a greater degree during alcohol cue presentation, lower white matter integrity in tracts that project to limbic and temporal regions (e.g., fornix, cingulate, and superior longitudinal fasciculus) may result in less effective control Inhibitors,research,lifescience,medical over representations in bottom-up processing streams. Notably, the fornix and cingulate are consistently implicated in studies of alcohol dependence (Schulte et al. 2010). Inhibitors,research,lifescience,medical A caveat to these interpretations is that several tracts, such as the superior longitudinal fasciculus, are quite large and are known to incorporate several subcomponents (Fernández-Miranda et al. 2008a; Schmahmann et al. 2008). Future studies examining

the relation of cue reactivity to specific subtracts would be useful. A recent study found that alcohol-dependent participants had lower gray matter volume of lateral frontal, medial frontal, and parietal-occipital COX signaling inhibitors clusters compared to healthy control participants and that volume of Dimethyl sulfoxide the medial frontal and parietal-occipital clusters significantly predicted time to relapse, after controlling for age, IQ, years of alcohol use, and consumption over the 90 days preceding treatment (Rando et al. 2011). The clusters that predicted relapse in that study were consistent with the clusters of BOLD activity in the anterior and posterior cingulate, precuneus/cuneus, and medial prefrontal cortex associated with lower FA in our study.