An Investigation of Working Memory: Influences of COMT, Sex, and Urbanicity on Cognitive Performance and Neuroimaging Measures

Abstract

Working memory is involved in numerous areas of cognition. It has been studied using various tasks, in which cognitive performance and brain activation have been measured. Working memory depends largely on dopamine function in the prefrontal cortex. Working memory ability and underlying brain function can be influenced by genetic and environmental factors. A major genetic influence on prefrontal dopamine levels and related cognitive processes is the catechol-O-methyltransferase (COMT) gene, and specifically the COMT Val108/158Met single nucleotide polymorphism. We investigated associations between COMT genotype and working memory, along with how such associations can be moderated by sex and childhood urbanicity (i.e., being raised in an urban environment). In the first study, we tested whether performance differed between COMT genotypes as working memory load was increased to highly demanding levels. Using three working memory tasks, we found that the effect of increasing working memory load did not differ between COMT genotypes, and there were also no main effects of COMT on performance across loads. The second study examined the interaction between COMT genotype and sex on working memory performance. Our results showed main effects of sex on accuracy across all three tasks, particularly as load became more demanding. We also found COMT effects on reaction time specific to one task and a COMT-by-sex interaction specific to accuracy at high load. In our third study, we investigated associations between COMT and childhood urbanicity on prefrontal brain function during working memory using functional magnetic resonance imaging. Here we found the expected main effect of COMT, as well as a novel main effect of urbanicity in which subjects who were raised in urban environments showed relatively inefficient prefrontal functioning in adulthood. In addition, there was an intriguing interaction between COMT and urbanicity; the well-established effect of COMT genotype on prefrontal efficiency was reversed in individuals with an urban upbringing. Together these studies demonstrate how cognitive performance and brain activation during working memory can be impacted by both innate and environmental factors.