Alcohol-related disruptions of cerebellar contributions to cognition: a longitudinal study of cerebellar volume in twins

Abstract

Our limited understanding of the human cerebellum once relegated it to a role of motor coordination. Over the past several decades, however, our conceptualization has expanded and now includes cerebellar contributions to “higher order” functions, such as cognition and emotion. The accumulating evidence for cerebellar involvement in cognition underscores the need to better understand the association between alcohol misuse and cerebellar structure and functioning. However, methodological shortcomings of previous research, including small sample sizes and over-reliance on case-control research designs, have hindered our understanding of these associations. To address these and other limitations in the literature, this dissertation was designed to first establish the presence of associations between cerebellar volume and neurocognitive functioning and to then investigate whether alcohol use in adolescence and emerging adulthood disrupts cerebellar volume. This work relies on a relatively large (N=437) population-based twin sample, whose substance use, cognitive functioning, and cerebellar volume were carefully assessed. The use of data from twins allowed us to employ a quasi-experimental research technique, the co-twin control analysis, in a field where true experimentation is unfeasible. In Study 1, consistent with previous research, we found evidence for an association of cerebellar volume and neurocognitive functioning, particularly working memory and processing speed, in young adulthood. This finding supports the theory of a generalized role of the human cerebellum in predictive processing. In study two, we found evidence that alcohol use in adolescence negatively predicts cerebellar volume in young adulthood. This association was present among males but not females. Importantly, results of follow-up co-twin control analyses suggested that this association was likely due to genetic confounding, rather than to exposure to alcohol. This finding has important implications for preventative and intervention efforts aimed at the reduction of early alcohol use. Taken together, this work contributes to our understanding of how alcohol misuse affects the brain and interferes with its ability to carry out its neurocognitive functions.