2012a). Taken together, previous studies suggest that alcohol-related white matter abnormality occurs in broadly distributed white matter tracts, yet it may preferentially affect networks regulating motivation and reward salience (Harris et al. 2008; Pfefferbaum et al.

2009; Yeh et al. 2009). Evidence of widespread white matter damage in AUDs raises questions about the functional import of these changes. A study that classified participants Inhibitors,research,lifescience,medical who completed AUD treatment as returning to heavy use or sustaining treatment gains at 6-month follow-up found significantly higher FA in frontal white matter at baseline in the treatment sustainers (Sorg et al. 2012). This association Inhibitors,research,lifescience,medical between baseline white matter integrity and treatment outcome suggests that the role of white matter in AUDs warrants further attention. A possible mechanism relating white matter integrity to susceptibility to alcohol problems is that alcohol may disrupt top-down, behavioral regulation networks that modulate reactivity to environmental cues, including alcohol

stimuli. This study approached this issue by examining the association between white matter integrity and neural reactivity to an alcohol taste cue in heavy drinkers. It has been hypothesized that alcohol affects the neuronal Inhibitors,research,lifescience,medical networks that underlie reward-based learning and executive control, Inhibitors,research,lifescience,medical both of which have been implicated in the development of substance dependence (Koob and Volkow 2010). At the network level, decreased white matter integrity may produce disconnection or otherwise alter function in cortical and subcortical reward substrates. In particular, alcohol may sensitize subcortical c-Met inhibitor systems

involved in reward or approach behavior while it dampens frontoparietal cortical networks important for self-regulation (Koob and Volkow 2010). Given findings of premorbid abnormality in white matter integrity and functional connectivity of Inhibitors,research,lifescience,medical frontoparietal and frontocerebellar networks, it seems tuclazepam likely that some structural and functional liabilities to problem drinking predate the use of alcohol (Herting et al. 2010, 2011; Wetherill et al. 2012). A model that takes into account both premorbid vulnerability to and direct effects of alcohol is consistent with models of addiction that describe an overactive incentive motivational network in conjunction with a compromised control network (Volkow et al. 2002; Kalivas and Volkow 2005; Baler and Volkow 2006; Wiers et al. 2007; Hutchison 2010). Multimodal neuroimaging approaches that combine functional MRI (fMRI) and DTI are ideally suited to address the ramifications of white matter network abnormality.