Alcohol Use Disorder (AUD) is a chronic relapsing disease that has a major public health impact. The neurobiology of AUD remains poorly understood, and pharmacotherapies to treat the disorder are only moderately effective. One reason for these barriers are the difficulties in modeling AUD phenotypes, including impulsivity and compulsivity. Impulsivity, the predisposition towards poorly planned actions, is increased in individuals with addictive disorders. Compulsivity, the continuation of drug use despite adverse consequences, is a hallmark of addictive disorders. While impulsivity has been studied in clinical populations, compulsivity has been largely unstudied, due to methodological limitations. Using neuroimaging techniques, I explore the phenotypes of impulsivity and compulsivity in heavy alcohol users. First, I used structural MRI to investigate the morphometry of two regions, the anterior insula (AI) and anterior cingulate cortex (ACC), which are implicated in AUD as well as involved in impulsivity and compulsivity. Individuals with AUD had aberrant structural morphometry of these regions compared to light drinking healthy controls. Moreover, structural morphometry of the AI and ACC was negatively associated with impulsivity and compulsivity measures, such that alcohol dependent individuals with smaller and thinner AIs and ACC also reported higher levels of impulsivity and compulsivity. Next, I investigated the neural substrates of behavioral compulsivity in heavy and light alcohol users. Heavy drinkers engaged in more compulsive alcohol seeking than light drinking individuals. Behavioral compulsive alcohol seeking was positively associated with self-report drinking compulsivity. Compulsive alcohol seeking was associated with a hyperactive neural circuit involving the AI, ACC, and the dorsal and ventral striatum in heavy drinkers. Collectively, these findings demonstrate that fronto-striatal circuitry is implicated in impulsivity and compulsivity in heavy alcohol users. Moreover, these results suggest that disruption of fronto-striatal circuitry in individuals with AUD represents a potential treatment target, particularly for individuals with high levels of compulsivity.
Grodin, Erica Nicole,
"The Neural Correlates of Impulsivity and Compulsivity in Alcohol Dependence"
(2018).
Neuroscience Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://doi.org/10.26300/41dn-a033
