Drug addiction is a destructive disorder that frequently begins in adolescence and persists throughout a lifetime. A premise of this work is that understanding the neural basis of drug addiction, including its etiology and consequences, is essential to the prevention and treatment of drug use disorders. Network-level analyses of functional magnetic resonance imaging (fMRI) data investigated the neural correlates of risk for drug addiction associated with childhood maltreatment and characterized the drug-addicted state, specifically in cocaine-dependent men. Independent component analyses (ICA) identified candidate task-related neural processing networks for further investigation. In a study of non-drug abusing men and women, childhood trauma histories were associated with a sex-specific functional reorganization of a brain network related to motor response inhibition. Using graph theoretical and structural equation modeling analyses, extent of reorganization was associated with individual differences in response inhibition, dependent upon severity of childhood trauma exposure and sex. Neural network alterations associated with childhood maltreatment were attributed to adaptive or maladaptive mechanisms indicative of resilience or risk for addiction. In addition, neural network activation during motor response inhibition discriminated cocaine-dependent from non-drug abusing males, providing a pattern classifier that performed with high accuracy in cross validation and in classification of an independent sample. The classifier for cocaine addiction was positively correlated with both years of cocaine use and a measure of impulsiveness. This dissertation research provides novel insight into neural network alterations associated with childhood trauma and cocaine dependence, identifying neurophenotypes of risk for addiction and its functional impairments.
|Commitee:||Borders, Tyrone, James, G. Andrew, Kramer, Teresa, Oliveto, Alison|
|School:||University of Arkansas for Medical Sciences|
|Department:||Interdisciplinary Biomedical Sciences|
|School Location:||United States -- Arkansas|
|Source:||DAI-B 74/06(E), Dissertation Abstracts International|
|Keywords:||Addiction, Childhood trauma, Drugs, Fmri, Inhibitory control, Stop signal task|
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