The Effects of Alcohol and Cannabis Use on Inhibitory Control Brain Networks In Emerging Adulthood: Causal Inferences From A Cotwin Control Study

Abstract

The overarching theme of this dissertation was to separate the causal influences of familial risk toward substance misuse (e.g., genetic liability) from the potential effects of alcohol and cannabis exposure on multi-method indicators of the (pre)frontal inhibitory control brain network in a sample of 24-year-old twins. Deficits in inhibitory control and measures of its underlying brain circuitry have been implicated as core phenotypes of substance misuse. Research often assumes an exposure effect of alcohol or cannabis misuse on the still-developing emerging adult (ages 18-25) brain, but these individual differences may reflect the familial (e.g., genetic) risk toward both substance use and brain deviations. This remains largely unknown as the vast majority of prior work used research designs that could not disentangle exposure from risk. To address this and other limitations in the literature at large, this dissertation was designed to study how alcohol and cannabis use during emerging adulthood affect the structure and function of the inhibitory control network. We used a large (N = 673) genetically informative population-based twin sample, careful phenotyping of alcohol and cannabis use, multi-method brain assessment (EEG; structural MRI; resting-state fMRI connectivity), and a quasi-experimental research design (cotwin control analysis) to draw causal inferences regarding the effect of alcohol/cannabis use on the brain in a field where true experimentation is often unfeasible. Across the three studies in this dissertation, we found evidence that alcohol and/or cannabis use were associated with deviations in EEG theta-band rhythms, cortical thickness, and resting-state functional connectivity measures of the (pre)frontal inhibitory control network. The cotwin control analyses offered evidence that some of the anomalies can be attributed to consequences of alcohol and cannabis exposure, while others primarily reflect the liability to misuse alcohol or cannabis. Interestingly, deviations in the frontal medial cortex, a key hub of the control-related circuit, were implicated across all three studies, suggesting that it may play a crucial role in substance-related disinhibition. The work collectively suggests that substance-related variations in the inhibitory control brain network reflect a mixture of premorbid brain-based characteristics of familial risk and the deleterious effects of alcohol/cannabis exposure. Findings have implications for informing and shaping policy, public messaging, and prevention efforts to curb the alarmingly high rates of alcohol and cannabis use in emerging adults.