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Neural Connectivity and the Transition to Alcohol Dependence

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The advent of functional magnetic resonance imaging (fMRI) has profoundly advanced understanding of the human brain. One of the most exciting cutting-edge applications of fMRI is connectivity analysis, which reveals not only the separate brain regions involved in a given neural process, but also the manner in which these regions interact with each other. Dysfunction in such interactions is arguably the crux of human psychopathology. Connectivity analysis may particularly advance understanding of the neurobiology of alcohol dependence (alcoholism), a progressive, chronically relapsing disease that affects eight million Americans annually. The disease often begins with reward-driven heavy drinking and ultimately develops into a pattern of habitual, compulsive use. Animal models of addiction suggest that one key factor in this transition is a pervasive shift in the connectivity of the brain's behavioral control system. Initially, drinking may co-opt a brain network that underlies goal-directed (reward-motivated) behavior. After dependence onsets, drinking may shift to a network that mediates habit learning, or compulsivity. Human fMRI studies suggest that these networks are active when individuals are exposed to alcohol cues and also when they are at rest. Further, their integrity may be related to neurocognitive deficits in executive functioning. However, these networks have not been studied systematically in human alcoholics. This proposal will use fMRI connectivity analysis to test connectivity of the goal-directed and habit learning networks among non-dependent heavy drinkers and alcohol-dependent individuals. There are three specific aims: 1) to identify the connectivity differences between these groups during alcohol cue reactivity; 2) to identify such differences between groups while at rest; and 3) to determine whether connectivity differences are related to individual differences in neurocognitive impairment. Understanding shifts in the dominance of brain networks subserving reward and habit will ultimately contribute to the development of more efficacious treatments for alcohol dependence.
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