Date

12-2016

Document Type

Dissertation

Degree Name

Ph.D.

Department

Behavioral Neuroscience

Abstract

Alcohol consumption in the United States is unevenly distributed, with 64% of adults consuming alcohol but 8% meeting criteria for alcohol abuse. Many risk factors leading to excessive alcohol drinking have been identified, including aggressive and anxious temperaments, which can be studied in both human and non-human primate populations. However, aggression and anxiety have also been identified as consequences of heavy alcohol use in both human and animal populations. The functional neural correlates of aggressive and anxious temperaments have not been identified, although a network encompassing the amygdala and prefrontal cortical areas (see Figure 1) has been associated with anxious and aggressive behavior and alcohol dependence in humans. Longitudinal studies examining relationships between emotionally dysregulated behaviors and their associated neural correlates have not been performed, and can further understanding of the emergence and progression of alcohol dependence.

Thus, the goal of these studies was to explore associations between temperament, connectivity at rest between the amygdala and prefrontal cortex, and heavy ethanol self-administration and intoxication. Specifically, this dissertation aimed to identify the functional brain network modulating aggressive, anxious, and inhibited temperaments at rest, to determine in-vivo neural correlates of risk for progression to heavy drinking, and to assess changes in aggressive behavior and functional connectivity following chronic ethanol consumption in rhesus and cynomolgus macaques using resting state functional connectivity magnetic resonance imaging (rs-fcMRI).

The results of these studies suggest that highly aggressive rhesus macaques are uniquely at risk for becoming heavy ethanol drinkers, but that chronic ethanol access decreases aggression and anxiety (observed during the descending limb of intoxication) in both species. While extreme reactivity to threat and heavy ethanol drinking were both associated with alterations in intrinsic amygdalocortical connectivity prior to ethanol exposure in rhesus macaques, the neural correlates of aggression and future heavy drinking at baseline differed. Aggression was associated with anticorrelated connectivity between the basal amygdalar nucleus and dorsolateral prefrontal cortex, whereas future heavy drinking was associated with higher positive connectivity between the basal amygdalar nucleus and orbitofrontal cortex and central amygdalar nucleus and dorsolateral prefrontal cortex. Importantly, alterations in the intrinsic amygdalocortical connectivity associated with risk for heavy drinking were observed after chronic heavy ethanol self-administration.

These results suggest that although a single specific alteration in amygdalocortical connectivity at rest does not mediate the relationship between aggression and heavy ethanol intake, significant associations between amygdalocortical connectivity, temperament, and ethanol intake can be found in macaques. These studies provide insight into behavior and brain connectivity as risk factors versus consequences of heavy ethanol use to inform future research to improve identification and treatment of at-risk individuals.

Identifier

doi:10.6083/M4Z60N5P

School

School of Medicine

Available for download on Sunday, December 01, 2019

Included in

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