Cortical Connectivity in Alcoholism

Abstract

Alcoholism carries significant personal and societal burdens, and yet we still lack effective treatments for alcohol use disorders. Several lines of research have demonstrated disruption of major white matter (WM) tracts in the brains of detoxified alcoholics. Additionally, there are several reports of alterations in the dopaminergic system of alcoholics. A better understanding of the relationships of brain structure and function in the alcoholic brain is necessary to move toward more efficacious pharmacological interventions. In this dissertation, there are three main chapters. First, reduced WM integrity was reported in a sample of individuals with active alcohol use disorder (AUD). This is a relatively understudied population, which is believed to represent a less severe phenotype compared to the in-treatment samples that are typically studied. Second, higher WM integrity was reported in a sample of college-age, active AUD. In a subsample of these individuals, graph theory measures of structural brain network connectivity were shown to be altered in cigarette-smoking social-drinking controls and smoking AUD subjects, compared to nonsmoking healthy individuals. Finally, a novel multimodal approach that combines diffusion weighted imaging and [11C]raclopride positron emission tomography identified differential relationships between frontostriatal connectivity and striatal dopamine tone in active AUD versus social-drinking controls. This suggests that aberrations in frontostriatal connectivity may contribute to reported differences in dopaminergic function in AUD. In summary, these results show that similar to detoxified/in-treatment alcoholics, active AUD samples present with WM integrity alterations, and changes in both structural connectivity and frontostriatal structure/function relationships.